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1.
BMC Pregnancy Childbirth ; 24(1): 424, 2024 Jun 13.
Article in English | MEDLINE | ID: mdl-38872116

ABSTRACT

OBJECTIVE: To establish the population pharmacokinetics (PPK) of magnesium sulfate (MgSO4)in women with preeclampsia (PE), and to determine the key covariates having an effect in magnesium pharmacokinetics in Chinese PE. METHODS: Pregnant women with PE prescribed MgSO4 were enrolled in this prospective study from April 2021 to April 2023. On the initial day of administration, the patients were administered a loading dose of 5 g in conjunction with 10 g of magnesium sulfate as a maintenance dose. On the second day, only the maintenance dose was administration, and maternal blood samples were taken at 0, 4, 5, and 12 h after the second day's 10 g maintenance dose. The software Phoenix was used to estimate PPK parameters of MgSO4, such as clearance (CL) and volume of distribution (V), and to model PPK models with patient demographic, clinical, and laboratory covariates. RESULTS: A total of 199 blood samples were collected from 51 women with PE and PPK profiles were analyzed. The PPK of MgSO4 is consistent with to a one-compartment model. The base model adequately described the maternal serum magnesium concentrations after magnesium administration. The population parameter estimates were as follows: CL was 2.98 L/h, V was 25.07 L. The model predictions changed significantly with covariates (BMI, creatinine clearance, and furosemide). Furosemide statistically influences V. The creatinine clearance, BMI and furosemide jointly affects CL. Monte Carlo simulation results showed that a loading dose combined with a maintenance dose would need to be administered daily to achieve the therapeutic blood magnesium concentrations. For the non-furosemide group, the optimal dosing regimen was a 5 g loading dose combined with a 10 g maintenance dose of MgSO4. For the furosemide group, the optimal dosing regimen was a 2.5 g loading dose combined with a 10 g maintenance dose of MgSO4. CONCLUSIONS: The magnesium PPK model was successfully developed and evaluated in Chinese preeclampsia population, and the dose optimization of MgSO4 was completed through Monte Carlo simulation.


Subject(s)
Magnesium Sulfate , Pre-Eclampsia , Humans , Female , Magnesium Sulfate/administration & dosage , Magnesium Sulfate/pharmacokinetics , Pre-Eclampsia/drug therapy , Pre-Eclampsia/blood , Pregnancy , Adult , Prospective Studies , China , Young Adult , Dose-Response Relationship, Drug , East Asian People
2.
J Pregnancy ; 2024: 1178220, 2024.
Article in English | MEDLINE | ID: mdl-38504794

ABSTRACT

Objective: To validate a model for predicting magnesium concentration in magnesium sulfate treatment in preeclampsia. Design: Retrospective cohort study. Setting. Three secondary care hospitals, one accepting neonates from gestational week 28 + 0. Population. Women with preeclampsia undergoing magnesium sulfate treatment. Subjects initially received Zuspan treatment (4 g bolus and 1 g/h maintenance dose), commonly increased by individual titration. Main Outcome Measures. Difference in mean between measured and predicted magnesium concentration. Proportion of women reaching target concentration (>2 mM) in 25 h. Results: 56 women were included, with 356 magnesium measurements available. Mean magnesium concentration was 1.82 mM. The prediction model overestimated magnesium concentration by 0.10 mM (CI 0.04-0.16) but exhibited no bias for weight, creatinine, or treatment duration. Weighted mean infusion rate was 1.22 g/h during 30 hours. Overall success rate in reaching target concentration was 54%, decreasing to 40% in women > 95 kg. Overall success rate at 8 hours was 11%. No toxic concentrations were found. Conclusions: Zuspan regimen is very safe, but slow to reach therapeutic concentrations-despite efforts of individual titration. Success rate is lower in heavy women, which is of particular importance considering their predisposition to develop preeclampsia. The validated pharmacokinetic model performs well and may be used to individually tailor treatment from the outset.


Subject(s)
Pre-Eclampsia , Pregnancy , Infant, Newborn , Female , Humans , Pre-Eclampsia/drug therapy , Magnesium Sulfate/therapeutic use , Magnesium Sulfate/pharmacokinetics , Magnesium , Retrospective Studies , Outcome Assessment, Health Care
3.
Drugs R D ; 20(3): 257-266, 2020 Sep.
Article in English | MEDLINE | ID: mdl-32642964

ABSTRACT

BACKGROUND AND OBJECTIVE: The pharmacokinetic basis of magnesium sulphate (MgSO4) dosing regimens for preeclampsia (PE) prophylaxis and treatment is not clearly established. The aim of study is to develop a population pharmacokinetic (PK) model of MgSO4 in PE, and to determine key covariates having an effect in MgSO4 pharmacokinetics in preeclampsia (PE) and to determine key covariates having an effect in MgSO4 PK. METHODS: A prospective cohort study was conducted from June 2016 to February 2018 in patients with PE administered MgSO4 as a 4-g bolus followed by continuous infusion at a rate of 1 g/h. Serum magnesium concentrations were obtained before treatment administration and 2, 6, 12, and 18 h after the initial dose. The software Monolix was used to estimate population PK parameters of MgSO4 [clearance (CL), volume of distribution (V), half-life] and to develop a PK model with baseline patient demographic, clinical, and laboratory covariates. RESULTS: The study population consisted of 109 patients. The PK profile of MgSO4 was adequately described by a one-compartment PK model. The model estimate of the population CL was 1.38 L/h; for V, it was 13.3 L; and the baseline magnesium concentration was 0.77 mmol/L (1.87 mg/dL). The baseline body weight and serum creatinine statistically influenced MgSO4 CL and V, respectively. The model was parameterized as CL and V. CONCLUSION: The PK of MgSO4 in pregnant women with PE is significantly affected by creatinine and body weight. Pregnant women with PE and higher body weight have a higher V and, consequently, a lower elimination rate of MgSO4. Pregnant women with PE and a higher serum creatinine value show lower CL and, therefore, lower MgSO4 elimination rate.


Subject(s)
Anticonvulsants/pharmacokinetics , Magnesium Sulfate/pharmacokinetics , Pre-Eclampsia/blood , Adolescent , Adult , Anticonvulsants/administration & dosage , Anticonvulsants/blood , Clinical Protocols , Cohort Studies , Female , Humans , Infusions, Intravenous , Magnesium Sulfate/administration & dosage , Magnesium Sulfate/blood , Pre-Eclampsia/drug therapy , Pre-Eclampsia/prevention & control , Pregnancy , Prospective Studies , Young Adult
4.
J Vet Pharmacol Ther ; 43(4): 355-363, 2020 Jul.
Article in English | MEDLINE | ID: mdl-32144805

ABSTRACT

Magnesium may be used as an adjunctive analgesic for perioperative pain management because of its antinociceptive properties. This study investigated the analgesic efficacy of intraperitoneal ropivacaine combined with magnesium sulfate in canine ovariohysterectomy. Forty-five dogs sedated with acepromazine/meperidine and anesthetized with propofol/isoflurane were randomly distributed into three treatments, administered intraperitoneally (n = 15 per group): saline solution (group S), 0.25% ropivacaine (3 mg/kg) alone (group R), or in combination with magnesium sulfate (20 mg/kg, group R-Mg). Intravenous fentanyl was given to control cardiovascular responses to surgical stimulation. Postoperative pain was assessed using an Interactive Visual Analog Scale (IVAS), the short form of the Glasgow Composite Pain Scale, and mechanical nociceptive thresholds. Morphine/meloxicam was administered as rescue analgesia. Intraoperatively, the R-Mg group required less fentanyl (p = .02) and exhibited higher incidence of hypotension (systolic arterial pressure <90 mm Hg, p = .006) compared with the S group. Lower IVAS pain scores were recorded during the first hour in the R-Mg group than the other groups (p = .007-.045). Postoperative rescue analgesia did not differ between groups. Intraperitoneal magnesium sulfate administration, in spite of decreasing intraoperative opioid requirements, increased the incidence of hypotension with minimal evidence of postoperative analgesic benefits.


Subject(s)
Analgesics/therapeutic use , Anesthetics, Local/therapeutic use , Dog Diseases/prevention & control , Magnesium Sulfate/therapeutic use , Pain, Postoperative/veterinary , Ropivacaine/therapeutic use , Analgesics/administration & dosage , Analgesics/pharmacology , Anesthetics, Local/administration & dosage , Anesthetics, Local/pharmacology , Animals , Dogs , Drug Synergism , Female , Fentanyl/administration & dosage , Fentanyl/pharmacology , Hysterectomy/adverse effects , Hysterectomy/veterinary , Magnesium Sulfate/administration & dosage , Magnesium Sulfate/pharmacokinetics , Meloxicam/administration & dosage , Meloxicam/therapeutic use , Morphine/administration & dosage , Morphine/therapeutic use , Ovariectomy/adverse effects , Ovariectomy/veterinary , Pain, Postoperative/prevention & control , Perioperative Care , Ropivacaine/administration & dosage , Ropivacaine/pharmacokinetics
5.
BMC Anesthesiol ; 19(1): 237, 2019 12 20.
Article in English | MEDLINE | ID: mdl-31862004

ABSTRACT

BACKGROUND: The infusion of magnesium sulfate is well known to reduce arterial pressure and attenuate hemodynamic response to pneumoperitoneum. This study aimed to investigate whether different doses of magnesium sulfate can effectively attenuate the pneumoperitoneum-related hemodynamic changes and the release of vasopressin in patients undergoing laparoscopic gastrointestinal surgery. METHODS: Sixty-nine patients undergoing laparoscopic partial gastrectomy were randomized into three groups: group L received magnesium sulfate 30 mg/kg loading dose and 15 mg/kg/h continuous maintenance infusion for 1 h; group H received magnesium sulfate 50 mg/kg followed by 30 mg/kg/h for 1 h; and group S (control group) received same volume 0.9% saline infusion, immediately before the induction of pneumoperitoneum. Systemic vascular resistance (SVR), cardiac output (CO), mean arterial pressure (MAP), heart rate (HR), central venous pressure (CVP), serum vasopressin and magnesium concentrations were measured. The extubation time, visual analogue scale were also assessed. The primary outcome is the difference in SVR between different groups. The secondary outcome is the differences of other indicators between groups, such as CO, MAP, HR, CVP, vasopressin and postoperative pain score. RESULTS: Pneumoperitoneum instantly resulted in a significant reduction of cardiac output and an increase in mean arterial pressure, systemic vascular resistance, central venous pressure and heart rate in the control group (P <  0.01). The mean arterial pressure (T2 - T4), systemic vascular resistance (T2 - T3), central venous pressure(T3-T5) and the level of serum vasopressin were significantly lower (P <  0.05) and the cardiac output (T2 - T3) was significantly higher (P <  0.05) in group H than those in the control group. The mean arterial pressure (T4), systemic vascular resistance (T2), and central venous pressure(T3-T4) were significantly lower in group H than those in group L (P <  0.05). Furthermore, the visual analog scales at 5 min and 20 min, the level of vasopressin, and the dose of remifentanil were significantly decreased in group H compared to the control group and group L (P <  0.01). CONCLUSION: Magnesium sulfate could safely and effectively attenuate the pneumoperitoneum-related hemodynamic instability during gastrointestinal laparoscopy and improve postoperative pain at serum magnesium concentrations above 2 mmol/L. TRIAL REGISTRATION: The study was retrospectively registered at Chinese Clinical Trial Registry; the registration number is ChiCTR-IPD-17011145, principal investigator: D.Y. Q., date of registration: April 13, 2017.


Subject(s)
Gastrectomy/methods , Laparoscopy/methods , Magnesium Sulfate/administration & dosage , Pneumoperitoneum, Artificial/methods , Adult , Aged , Dose-Response Relationship, Drug , Double-Blind Method , Hemodynamics/drug effects , Hemodynamics/physiology , Humans , Magnesium Sulfate/pharmacokinetics , Middle Aged , Pain, Postoperative/epidemiology , Pneumoperitoneum, Artificial/adverse effects , Vasopressins/metabolism
6.
J Clin Pharmacol ; 59(11): 1519-1526, 2019 11.
Article in English | MEDLINE | ID: mdl-31157410

ABSTRACT

Magnesium sulfate is the anticonvulsant of choice for eclampsia prophylaxis and treatment; however, the recommended dosing regimens are costly and cumbersome and can be administered only by skilled health professionals. The objectives of this study were to develop a robust exposure-response model for the relationship between serum magnesium exposure and eclampsia using data from large studies of women with preeclampsia who received magnesium sulfate, and to predict eclampsia probabilities for standard and alternative (shorter treatment duration and/or fewer intramuscular injections) regimens. Exposure-response modeling and simulation were applied to existing data. A total of 10 280 women with preeclampsia who received magnesium sulfate or placebo were evaluated. An existing population pharmacokinetic model was used to estimate individual serum magnesium exposure. Logistic regression was applied to quantify the serum magnesium area under the curve-eclampsia rate relationship. Our exposure-response model-estimated eclampsia rates were comparable to observed rates. Several alternative regimens predicted magnesium peak concentration < 3.5 mmol/L (empiric safety threshold) and eclampsia rate ≤ 0.7% (observed response threshold), including 4 g intravenously plus 10 g intramuscularly followed by either 8 g intramuscularly every 6 hours × 3 doses or 10 g intramuscularly every 8 hours × 2 doses and 10 g intramuscularly every 8 hours × 3 doses. Several alternative magnesium sulfate regimens with comparable model-predicted efficacy and safety were identified that merit evaluation in confirmatory clinical trials.


Subject(s)
Anticonvulsants/administration & dosage , Anticonvulsants/pharmacokinetics , Magnesium Sulfate/administration & dosage , Magnesium Sulfate/pharmacokinetics , Pre-Eclampsia/drug therapy , Adult , Eclampsia , Female , Humans , Magnesium Sulfate/blood , Pregnancy
7.
Curr Opin Obstet Gynecol ; 31(2): 110-115, 2019 04.
Article in English | MEDLINE | ID: mdl-30747745

ABSTRACT

PURPOSE OF REVIEW: The aim of this review is to describe the proposed mechanisms of action of magnesium sulfate for fetal neuroprotection, different dosing regimens of the drug that have shown benefit, and to review recent pharmacokinetic studies of the drug to better inform clinicians regarding expected benefits and remaining research questions. RECENT FINDINGS: Retrospective secondary analysis of the beneficial effects of antenatal magnesium sulfate trial database and prospective pharmacokinetic/pharmacodynamic modeling indicate magnesium sulfate administration for duration longer than 18 h, given within 12 h of delivery, and maintaining a maternal serum level of 4.1 mg/dl may maximize the neuroprotective benefits of the drug. SUMMARY: Magnesium sulfate in some dosage given before very preterm pregnancy delivery is beneficial for fetal neuroprotection. The exact dose, duration, and timing of administration to maximize this benefit may be more precisely studied using pharmacokinetic/pharmacodynamic modeling techniques before conducting larger randomized trials.


Subject(s)
Central Nervous System Diseases/prevention & control , Infant, Premature, Diseases/prevention & control , Magnesium Sulfate/administration & dosage , Neuroprotective Agents/administration & dosage , Prenatal Care , Central Nervous System Diseases/physiopathology , Dose-Response Relationship, Drug , Female , Humans , Infant, Premature, Diseases/physiopathology , Magnesium Sulfate/pharmacokinetics , Magnesium Sulfate/pharmacology , Maternal-Fetal Exchange , Neuroprotective Agents/pharmacokinetics , Neuroprotective Agents/pharmacology , Pregnancy , Premature Birth , Retrospective Studies , Risk Assessment
8.
Eur J Clin Pharmacol ; 75(1): 59-66, 2019 Jan.
Article in English | MEDLINE | ID: mdl-30259065

ABSTRACT

PURPOSE: Intravenous (IV) magnesium sulfate (MgSO4) is clinically useful as adjunct therapy in treating acute asthma exacerbations. Despite its clinical utility, the disposition of magnesium in children is poorly described. The purpose of this study is to describe the pharmacokinetics (PK) of ionized and total serum magnesium following IV MgSO4 administration in children with severe acute asthma. METHODS: Thirty-two children receiving 50 mg/kg IV MgSO4 for acute asthma exacerbations at Primary Children's Hospital in Salt Lake City, UT, were prospectively enrolled in the study. Blood samples were collected before, as well as 30 min and 2 h after each child's IV MgSO4 dose, and used to determine total serum and ionized magnesium concentrations. The collected data were analyzed using population PK techniques using NONMEM® software. RESULTS: Total serum magnesium concentrations were used to externally validate our previously published model constructed with retrospective data (median prediction error 10.3%, median absolute prediction error 18.1%). The mean (%CV) observed endogenous ionized magnesium concentration was calculated to be 6.0 mg/L (12%), approximately one third of the same value for endogenous total serum magnesium (17.6 mg/L (22%)) in this dataset. Weight was a significant predictor of both clearance and volume in a population PK model describing ionized magnesium concentrations. No adverse events were observed in this pediatric cohort. CONCLUSIONS: This prospective study supports and extends our previous PK analysis of total serum magnesium concentrations. Ionized and total serum magnesium followed similar PK profiles following IV MgSO4 administration in children. A single bolus infusion of IV MgSO4 was safe in this small sample of children receiving it for acute asthma.


Subject(s)
Anti-Asthmatic Agents/administration & dosage , Asthma/drug therapy , Magnesium Sulfate/administration & dosage , Models, Biological , Acute Disease , Adolescent , Anti-Asthmatic Agents/adverse effects , Anti-Asthmatic Agents/pharmacokinetics , Asthma/physiopathology , Child , Child, Preschool , Female , Hospitalization , Humans , Infusions, Intravenous , Magnesium Sulfate/adverse effects , Magnesium Sulfate/pharmacokinetics , Male , Prospective Studies , Severity of Illness Index , Time Factors
9.
J Clin Pharmacol ; 59(3): 374-385, 2019 03.
Article in English | MEDLINE | ID: mdl-30422321

ABSTRACT

Magnesium sulfate is the standard therapy for prevention and treatment of eclampsia. Two standard dosing regimens require either continuous intravenous infusion or frequent, large-volume intramuscular injections, which may preclude patients from receiving optimal care. This project sought to identify alternative, potentially more convenient, but similarly effective dosing regimens that could be used in restrictive clinical settings. A 2-compartment population pharmacokinetic (PK) model was developed to characterize serial PK data from 92 pregnant women with preeclampsia who received magnesium sulfate. Body weight and serum creatinine concentration had a significant impact on magnesium PK. The final PK model was used to simulate magnesium concentration profiles for the 2 standard regimens and several simplified alternative dosing regimens. The simulations suggest that intravenous regimens with loading doses of 8 g over 60 minutes followed by 2 g/h for 10 hours and 12 g over 120 minutes followed by 2 g/h for 8 hours (same total dose as the standard intravenous regimen but shorter treatment duration) would result in magnesium concentrations below the toxic range. For the intramuscular regimens, higher maintenance doses given less frequently (4 g intravenously + 10-g intramuscular loading doses with maintenance doses of 8 g every 6 hours or 10 g every 8 hours for 24 hours) or removal of the intravenous loading dose (eg, 10 g intramusculary every 8 hours for 24 hours) may be reasonable alternatives. In addition, individualized dose adjustments based on body weight and serum creatinine were proposed for the standard regimens.


Subject(s)
Magnesium Sulfate/administration & dosage , Magnesium Sulfate/pharmacokinetics , Pre-Eclampsia/drug therapy , Adult , Female , Humans , Infusions, Intravenous , Injections, Intramuscular , Pre-Eclampsia/epidemiology , Pregnancy
10.
J Crit Care ; 44: 419-423, 2018 04.
Article in English | MEDLINE | ID: mdl-29353118

ABSTRACT

BACKGROUND: Intravenous magnesium is routinely administered in intensive care units (ICU) to treat arrhythmias after cardiothoracic surgery. There are no data on the pharmacokinetics of continuous magnesium infusion therapy. OBJECTIVE: To investigate the pharmacokinetics of continuous magnesium infusion, focusing on serum and urinary magnesium concentration, volume of distribution and half-life. METHODS: We administered a 10 mmol bolus of magnesium-sulfate followed by a continuous infusion of 3 mmol/h for 12 h in twenty cardiac surgery patients. We obtained blood and urine samples prior to magnesium administration and after one, six, and 12 h. RESULTS: Median magnesium levels increased from 1.09 (IQR 1.00-1.23) mmol/L to 1.59 (1.45-1.76) mmol/L after 60 min (p < .001), followed by 1.53 (1.48-1.71) and 1.59 (1.48-1.76) mmol/L after 6 and 12 h. Urinary magnesium concentration increased from 9.2 (5.0-13.9) mmol/L to 17 (13.6-21.6) mmol/L after 60 min (p < .001). Cumulative urinary magnesium excretion was 28 mmol (60.9% of the dose given). The volume of distribution was 0.25 (0.22-0.30) L/kg. There were no episodes of severe hypermagnesemia (≥3 mmol/L). CONCLUSION: Combined bolus and continuous magnesium infusion therapy leads to a significant and stable increase in magnesium serum concentration despite increased renal excretion and redistribution.


Subject(s)
Anti-Arrhythmia Agents/pharmacokinetics , Cardiac Surgical Procedures , Kidney/physiology , Magnesium Sulfate/pharmacokinetics , Aged , Analysis of Variance , Anti-Arrhythmia Agents/administration & dosage , Arrhythmias, Cardiac/blood , Arrhythmias, Cardiac/drug therapy , Arrhythmias, Cardiac/urine , Critical Care/methods , Elective Surgical Procedures , Female , Humans , Infusions, Intravenous , Magnesium/blood , Magnesium/urine , Magnesium Sulfate/administration & dosage , Male , Middle Aged
11.
Eur J Clin Pharmacol ; 73(3): 325-331, 2017 Mar.
Article in English | MEDLINE | ID: mdl-27909740

ABSTRACT

PURPOSE: Intravenous (IV) magnesium sulfate (MgSO4) is used as adjunct therapy to treat acute asthma exacerbations. Despite its clinical use, there is a limited understanding of the disposition of magnesium in children. METHODS: To explore the pharmacokinetics (PK) of IV MgSO4 in this population, we collected retrospective data from 54 children who received IV MgSO4 for treatment of an acute asthma exacerbation at Primary Children's Hospital in Salt Lake City, UT. These data were analyzed using population PK modeling techniques in NONMEM® to determine sources of variability affecting the disposition of magnesium, as well as to predict the dose of IV MgSO4 needed to achieve clinical benefit. RESULTS: The covariate analysis found that only weight was a significant predictor of magnesium concentrations in children. Estimated model parameters suggested that magnesium exhibits a short serum half-life (2.7 h) in children. The average endogenous magnesium concentration (prior to administration of IV MgSO4) was estimated to be 21 mg/L. Simulated data suggested that doses between 50 and 75 mg/kg are required to achieve concentration-time profiles within a hypothesized target therapeutic range between 25 and 40 mg/L. CONCLUSIONS: These results provide new insight into the disposition of IV MgSO4 in children and provide dosing guidelines for future prospective studies of IV MgSO4 in children with acute asthma.


Subject(s)
Asthma/drug therapy , Magnesium Sulfate/pharmacokinetics , Acute Disease , Adolescent , Child , Child, Preschool , Female , Humans , Magnesium Sulfate/therapeutic use , Male , Severity of Illness Index
14.
Eur. j. anat ; 20(4): 319-328, oct. 2016. ilus, graf
Article in English | IBECS | ID: ibc-157764

ABSTRACT

Propofol-induced neurotoxicity in developing brain is an evolving problem. Magnesium is proved to be neuro-protective when administered antenatally in case of pre-eclampsia and eclampsia. The aim of this work is to investigate the protective role of magnesium sulphate (MgSO4) against propofol-induced neurotoxicity in developing rats’ cerebral cortex (CC). Forty albino rats of the Sprague-Dawley strain aged 5 to 7 days were divided into four groups; Control group (Group A); MgSO4 group (Group B) receiving MgSO4 at a dose of 270 mgkg; Propofol group (Group C) receiving propofol at a dose of 20 mgkg; and Propofol+ MgSO4 group (Group D) receiving both drugs simultaneously. All drugs were given by intra-peritoneal (IP) injection. 48 hours following exposure, blood samples were collected from rats for cytochrome-c plasma assay. Also, Specimens from rats’ CC were processed for light microscopic examination. An immune-histo-chemical study was conducted using Glial Fibrillary Acidic Protein (GFAP) and Bcl-2-associated X protein (BAX).Propofol administration led to disruption of the cortical laminar architecture, with a significant decrease in the number of pyramidal cells. Also, GFAP and BAX immune-stained sections revealed a significant increase in the area percentage of their immune-reaction as compared to the control group, together with a significant increase in the serum level of cytochrome-c. Administration of MgSO4 with propofol could improve the histological picture of the cortex, including its laminar appearance and neuronal density. Also MgSO4 could decrease GFAP and BAX immune-reaction, with no change that could be noticed in the serum level of cytochrome-c. MgSO4 could be used as neuro-protective agent against propofol-induced cortical injury in infant rats


No disponible


Subject(s)
Animals , Rats , Magnesium Sulfate/pharmacokinetics , Propofol/adverse effects , Neurotoxicity Syndromes/prevention & control , Cerebral Cortex , Neuroprotective Agents/pharmacokinetics , Disease Models, Animal , Anesthetics/adverse effects , Cytochromes c/blood , Case-Control Studies
15.
Am J Obstet Gynecol ; 214(6): 737.e1-9, 2016 Jun.
Article in English | MEDLINE | ID: mdl-26767791

ABSTRACT

BACKGROUND: Magnesium sulfate is one of the most commonly prescribed intravenous medications in obstetrics. Despite its widespread use, there are limited data about magnesium pharmacokinetics, and magnesium is prescribed empirically without dose adjustment for different indications. OBJECTIVE: The aim of this study was to characterize the pharmacokinetics and placental transfer of magnesium sulfate in pregnant women and to determine key covariates that impact the pharmacokinetics. STUDY DESIGN: This is a prospective pharmacokinetic cohort study of pregnant women who were prescribed magnesium sulfate for preeclampsia, preterm labor, or extreme prematurity. Women received a 4-g loading dose and 2 g/h maintenance dose as clinically indicated. Maternal blood samples were obtained before and at multiple time points during and after magnesium administration. Cord blood also was sampled at delivery. A population pharmacokinetic approach that used a nonlinear mixed-effects modeling was used to characterize magnesium disposition. RESULTS: Pharmacokinetic profiles of 111 pregnant women were analyzed. Magnesium clearance was 3.98 L/h in preeclamptic women and 5.88 L/h non-preeclamptic women. Steady-state concentration of magnesium was 7.2 mg/dL in preeclamptic women compared with 5.1 mg/dL in non-preeclamptic women. Maternal weight significantly impacted time to steady state. The ratio of the mean umbilical vein magnesium level to the mean maternal serum magnesium level at the time of delivery was 0.94 ± 0.15. CONCLUSIONS: The study accurately characterizes the pharmacokinetics of magnesium administered to pregnant women. Preeclamptic status and maternal weight significantly impact serum magnesium levels. This pharmacokinetic model could be applied to larger cohorts to help tailor magnesium treatment and account for these covariates.


Subject(s)
Magnesium Sulfate/pharmacokinetics , Maternal-Fetal Exchange , Placenta/chemistry , Tocolytic Agents/pharmacokinetics , Adult , Body Weight , Female , Humans , Magnesium Sulfate/blood , Pre-Eclampsia/drug therapy , Pregnancy , Prospective Studies , Tocolytic Agents/blood , Umbilical Veins/chemistry
17.
BJOG ; 123(3): 356-66, 2016 Feb.
Article in English | MEDLINE | ID: mdl-26599617

ABSTRACT

BACKGROUND: The pharmacokinetic basis of magnesium sulphate (MgSO4 ) dosing regimens for eclampsia prophylaxis and treatment is not clearly established. OBJECTIVES: To review available data on clinical pharmacokinetic properties of MgSO4 when used for women with pre-eclampsia and/or eclampsia. SEARCH STRATEGY: MEDLINE, EMBASE, CINAHL, POPLINE, Global Health Library and reference lists of eligible studies. SELECTION CRITERIA: All study types investigating pharmacokinetic properties of MgSO4 in women with pre-eclampsia and/or eclampsia. DATA COLLECTION AND ANALYSIS: Two authors extracted data on basic pharmacokinetic parameters reflecting the different aspects of absorption, bioavailability, distribution and excretion of MgSO4 according to identified dosing regimens. MAIN RESULTS: Twenty-eight studies investigating pharmacokinetic properties of 17 MgSO4 regimens met our inclusion criteria. Most women (91.5%) in the studies had pre-eclampsia. Baseline serum magnesium concentrations were consistently <1 mmol/l across studies. Intravenous loading dose between 4 and 6 g was associated with a doubling of this baseline concentration half an hour after injection. Maintenance infusion of 1 g/hour consistently produced concentrations well below 2 mmol/l, whereas maintenance infusion at 2 g/hour and the Pritchard intramuscular regimen had higher but inconsistent probability of producing concentrations between 2 and 3 mmol/l. Volume of distribution of magnesium varied (13.65-49.00 l) but the plasma clearance was fairly similar (4.28-5.00 l/hour) across populations. CONCLUSION: The profiles of Zuspan and Pritchard regimens indicate that the minimum effective serum magnesium concentration for eclampsia prophylaxis is lower than the generally accepted level. Exposure-response studies to identify effective alternative dosing regimens should target concentrations achievable by these standard regimens. TWEETABLE ABSTRACT: Minimum effective serum magnesium concentration for eclampsia prophylaxis is lower than the generally accepted therapeutic level.


Subject(s)
Anticonvulsants/administration & dosage , Anticonvulsants/pharmacokinetics , Eclampsia/drug therapy , Magnesium Sulfate/administration & dosage , Magnesium Sulfate/pharmacokinetics , Pre-Eclampsia/drug therapy , Female , Humans , Pregnancy
18.
Xenobiotica ; 46(2): 184-91, 2016.
Article in English | MEDLINE | ID: mdl-26226518

ABSTRACT

1. Sulphonation is unusual amongst the common Phase II (condensation; synthetic) reactions experienced by xenobiotics, in that the availability of the conjugating agent, sulphate, may become a rate-limiting factor. This sulphate is derived within the body via the oxygenation of sulphur moieties liberated from numerous ingested compounds including the sulphur-containing amino acids. Preformed inorganic sulphate also makes a considerable contribution to this pool. 2. There has been a divergence of opinion as to whether or not inorganic sulphate may be readily absorbed from the gastrointestinal tract and this controversy still continues in some quarters. Even more so, is the vexing question of potential absorption of inorganic sulphate via the lungs and through the skin. 3. This review examines the relevant diverse literature and concludes that sulphate ions may move across biological membranes by means of specific transporters and, although the gastrointestinal tract is by far the major portal of entry, some absorption across the lungs and the skin may take place under appropriate circumstances.


Subject(s)
Sulfates/pharmacokinetics , Administration, Inhalation , Animals , Gastrointestinal Tract/drug effects , Gastrointestinal Tract/metabolism , Humans , Magnesium Sulfate/administration & dosage , Magnesium Sulfate/pharmacokinetics , Models, Animal , Skin Absorption/drug effects , Sulfates/administration & dosage
19.
Indian J Pediatr ; 82(4): 321-7, 2015 Apr.
Article in English | MEDLINE | ID: mdl-24916134

ABSTRACT

OBJECTIVES: To determine the response of nebulized magnesium sulfate on the lung function of children with bronchial hyperresponsiveness. METHODS: Eighty-four children with asthma were divided into three groups randomly: magnesium sulfate (M), albuterol (A), and a combination of magnesium sulfate and albuterol (M + A). All patients were nebulized with acetylcholine, and then treated as designed. Lung function was compared between the three groups. RESULTS: Forced expiratory volume in first second (FEV1) significantly improved in all the three groups but it was better in (A) and (M + A) compared to (M) at 10 min and 20 min [10 min: 1.26 L ± 0.53 (A) vs. 1.10 L ± 0.27 (M), 1.35 L ± 0.59 (M + A) vs. 1.10 L ± 0.27 (M), p < 0.05; 20 min: 1.32 L ± 0.61 (A) vs. 1.17 L ± 0.30 (M), 1.42 L ± 0.59 (M + A) vs. 1.17 L ± 0.30 (M), p < 0.05]. Variation of FEV1, as absolute value at 10 min or 20 min over post-Ach FEV1 was significantly different in (A) or (M + A) compared to (M). CONCLUSIONS: Nebulized albuterol and magnesium sulfate + albuterol can more effectively improve FEV1 in children with bronchial hyperresponsiveness than nebulized magnesium sulfate at 10 min and 20 min after inhalation. It is further suggested that addition of magnesium sulfate to albuterol does not result in additional benefit.


Subject(s)
Albuterol , Magnesium Sulfate , Respiratory Hypersensitivity , Administration, Inhalation , Albuterol/administration & dosage , Albuterol/pharmacokinetics , Biological Availability , Bronchodilator Agents/administration & dosage , Bronchodilator Agents/pharmacokinetics , Child , Child, Preschool , Double-Blind Method , Drug Administration Schedule , Drug Monitoring/methods , Drug Therapy, Combination/methods , Female , Humans , Magnesium Sulfate/administration & dosage , Magnesium Sulfate/pharmacokinetics , Male , Nebulizers and Vaporizers , Respiratory Function Tests/methods , Respiratory Hypersensitivity/diagnosis , Respiratory Hypersensitivity/drug therapy , Respiratory Hypersensitivity/physiopathology , Treatment Outcome
20.
Pharm. pract. (Granada, Internet) ; 12(2): 0-0, abr.-jun. 2014. tab
Article in English | IBECS | ID: ibc-125674

ABSTRACT

Background: Preferred anticonvulsant used to treat and prevent fits in eclampsia currently is magnesium sulphate. Clinical monitoring of tendon reflexes, respiration rate and measuring hourly urine output should be done to ensures safe administration of magnesium sulphate Objective: This study was conducted to evaluate maternal outcomes of magnesium sulphate and diazepam use in the management of severe pre-eclampsia and eclampsia in Jimma University Specialized Hospital. Methods: A retrospective hospital based cross-sectional comparative study was conducted using data collection format. Data was collected from the hospital delivery care register and patient chart records of all pregnant women who presented with the diagnosis of severe pre-eclampsia and eclampsia in two years and three months period from January, 2010 to April, 2012. Data analysis was done by SPSS version 16.0. A P-value of <0.05 was considered statistically significant in all tests. Results: A total of 357 patient charts, 217 from magnesium sulphate and 140 from diazepam treatedpregnant women group, were reviewed and analyzed. Three pregnant women from the magnesium sulphate treated group and eleven pregnant women from diazepam treated group had at least one convulsion after taking the drug. Greater proportion of patients in the magnesium sulphate treated group had less than four days postpartum stay as compared to the diazepam treated patients (82.3% versus 66.2%). Seizure occurrence, duration of postpartum hospital stays and birth outcome had a statistically significant association with the type of anticonvulsant used. Conclusions: Magnesium sulphate is more effective than diazepam in the management of severe pre-eclamptic and eclamptic pregnant women in terms of seizure prevention, shortening postpartum hospital stay and reducing maternal morbidities (AU)


Antecedentes: El anticonvulsivante preferido para tratar y prevenir ataques en eclampsia es actualmente el sulfato de magnesio. Para garantizar una administración segura del sulfato de magnesio debería realizarse una monitorización clínica de los reflejos tendinales, velocidad de respiración y producción horaria de orina. Objetivo: Este estudio se realizó para evaluar los resultados maternos del uso de sulfato de magnesio y diazepam en el manejo de la pre-eclampsia y eclampsia graves en el Hospital especializado de la Universidad de Jimma. Métodos: Se realizó un estudio transversal retrospectivo mediante recogida de datos. Los datos se recogieron del registro de cuidados prestados en el hospital y de las historias clínicas de todas las embarazadas que presentaron diagnóstico de pre-eclampsia o eclampsia grave en los dos años y tres meses entre enero 2010 y abril 2012. El análisis se realizó con un SPSS versión 16.0. Se consideró significativo para todas las pruebas un p<0,05. Resultados: Se revisaron y analizaron un total de 357 historias clínicas de 217 pacientes tratados con sulfato de magnesio y 140 con diazepam. Tres embarazadas tratadas con sulfato de magnesio y 11 tratadas con diazepam habían tenido, al menos, una convulsión después de tomar el medicamento. La mayor proporción de pacientes tratadas con sulfato de magnesio tuvo menos de 4 días de estancia post-parto comparadas con las tratadas con diazepam (82,3% versus 66,2%). La aparición de convulsiones, la estancia hospitalaria post-parto y los resultados del parto tuvieron asociación estadísticamente significativa con el tipo de anticonvulsivante utilizado. Conclusiones: El sulfato de magnesio es más efectivo que el diazepam en el manejo de pre-eclampsia y eclampsia graves en términos de prevención de convulsiones, reducción de la estancia hospitalaria post-parto y reducción de las morbilidades maternas (AU)


Subject(s)
Humans , Female , Pregnancy , Magnesium Sulfate/pharmacokinetics , Diazepam/pharmacokinetics , Pre-Eclampsia/drug therapy , Eclampsia/drug therapy , Pregnancy Complications/drug therapy , Seizures/prevention & control , Length of Stay/statistics & numerical data
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