The Validation and Determination of Empagliflozin Concentration in the Presence of Grapefruit Juice Using HPLC for Pharmacokinetic Applications.

Type 2 diabetes mellitus is a multifactorial disorder whose primary manifestation usually initiates with elevated blood sugar levels. Several antidiabetic agents are used to manage type 2 diabetes mellitus, of which empagliflozin is an oral sodium-glucose co-transporter (SGLT-2) inhibitor in the kidney. This research aims to develop and validate a simple analytical method for determining empagliflozin levels in biological fluid and to further evaluate grapefruit juice's impact on empagliflozin pharmacokinetics in rats. High-Performance Liquid Chromatography (HPLC) was used to establish a simple, rapid, and accurate method for determining empagliflozin levels in rat plasma, in the presence of grapefruit juice. Four groups of rats (n = 10 rats in each) were used in the preclinical study. Group A (healthy rats) received empagliflozin alone; Group B (healthy rats) received empagliflozin with grapefruit; Group C (diabetic rats) received empagliflozin with grapefruit; and Group D (healthy, negative control) received no medication. The rats (n = 10) were given grapefruit juice instead of water for seven days before receiving the empagliflozin dose (0.16 mg/kg). Some pharmacokinetic parameters for each group were determined. The maximum plasma concentration (Cmax) and area under the curve (AUC) of empagliflozin in Group A without grapefruit intake were 730 ng/mL and 9264.6 ng × h/mL, respectively, with Tmax (2 h). In Group B, Cmax was 1907 ng/mL and AUC was 10,290.75 ng × h/mL in the presence of grapefruit, with Tmax (1 h); whereas, in Group C, the Cmax was 2936 ng/mL and AUC was 18657 ng × h/mL, with Tmax (2 h). In conclusion, our results showed that the co-administration of grapefruit with empagliflozin should be cautiously monitored and avoided, in which grapefruit elevates the plasma level of empagliflozin. This may be attributed to the inhibition of the uridine enzyme in the grapefruit by hesperidin, naringin, and flavonoid.

Pharmacokinetics and Pharmacodynamics: A Comprehensive Analysis of the Absorption, Distribution, Metabolism, and Excretion of Psychiatric Drugs.

The two main classifications of antidepressant medications are selective norepinephrine reuptake inhibitors (SNRIs) and selective serotonin reuptake inhibitors (SSRIs). Out of the available choices, selective serotonin reuptake inhibitors (SSRIs) have emerged as the most commonly prescribed option. The class demonstrates a greater degree of diversity in its structural characteristics in contrast to its neurochemical effects. Nevertheless, it is important to acknowledge that the chemical composition of a drug within this specific class does not carry substantial significance in the selection process. A comprehensive analysis of the pharmacodynamic and pharmacodynamic properties of antidepressant drugs proves advantageous for clinicians and managed care providers responsible for selecting preferred selective serotonin reuptake inhibitors (SSRIs) from a roster of authorized medications. The physicochemical characteristics, which possess considerable significance, are frequently disregarded except during the drug development stage. Pharmacodynamic properties refer to the physiological and biochemical effects that drugs exert on the human body. It is noteworthy that the inclusion of selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) in a comprehensive depression management protocol may demonstrate enhanced effectiveness in clinical environments as opposed to controlled trials.

Cytotoxicity Activity of Graviola Fruit Extract with Carbamazepine and Valproic Acid Show Antagonistic and Indifferent Effects.

OBJECTIVE: Graviola is a tropical fruit with medicinal properties, used for treating various diseases such as inflammation, diabetes, and cancer. Histone deacetylase inhibitors (HDACIs), including carbamazepine (CBZ) and valproic acid (VPA), have been proven strong inhibitors against cancer cell growth. This study investigated the effect of Graviola fruit extract (GFE) on CBZ in healthy rat plasma using high-performance liquid chromatography (HPLC). In addition, the effect of GFE in combination with CBZ and VPA on two human cancer cell lines (PC3 and MCF-7) was explored. METHODS: The CBZ levels were analyzed using a simple validated HPLC method. The linearity was achieved at a 0.9998 coefficient of determination over a range of 75-5000 ng/mL CBZ. The MTT assay was used to quantify the percentage of viable cells. RESULT: The maximum plasma concentration (Cmax) and area under the curve (AUC) for CBZ alone were 4,631 ng/mL and 49,225 ng. h/mL, respectively. However, in the presence of GFE, the values reduced significantly to 2,994 ng/mL and 26,587 ng. h/mL, while the p-value was <0.05. The 3-(4,5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide (MTT) assay results for VPA showed a weak cytotoxicity activity on PC3 and MCF-7 cell lines. CONCLUSION: A simple and validated HPLC method was used to determine CBZ levels in rats' plasma. The plasma CBZ levels (Cmax) were significantly reduced in the presence of GFE, indicating the importance of drug-herb interactions. For in vitro studies, two human cancer cell lines, MCF-7 (breast cancer cells) and PC3 (prostate cancer cells), were used to screen the cytotoxicity activity of GFE, CBZ, and VPA. We observed an antagonism effect for GFE and CBZ combination in both cell lines with FIC values > 4. On the contrary, the combination of GFE and VPA showed an additive or indifferent effect.

Real-World Effectiveness of Four Types of COVID-19 Vaccines.

BACKGROUND: There is a scarcity of evidence regarding the real-world effectiveness of coronavirus disease 2019 (COVID-19) vaccines. This was the first study to evaluate the effectiveness of four types of vaccines against asymptomatic and symptomatic infection, and COVID-19 outcomes among the general population. METHODS: This was a matched comparison group quasi-experimental study conducted in Jordan between 1 January and 29 August 2021. In the first part of the study, 1200 fully vaccinated individuals were matched with 1200 unvaccinated control participants. In order to measure vaccine effectiveness, the infection rates of both vaccinated and unvaccinated groups were calculated. The second part of the study included measuring specific anti-SARS CoV-2 immune cells and antibodies. RESULTS: BNT162b2 (Pfizer, New York, NY, USA) showed a significantly higher effectiveness against asymptomatic COVID-19 infection (91.7%) and hospitalization (99.5%) than BBIBP-CorV (Sinopharm, Beijing, China) (88.4% and 98.7%, respectively) and ChAdOx1 nCoV-19 (AstraZeneca, Cambridge, UK) (84.3%, and 98.9%, respectively). The effectiveness rates of the Sputnik V (Gamaleya Research Institute, Moscow, Russia) vaccine against asymptomatic, symptomatic, and hospitalization were 100%, 100%, and 66.7%, respectively. The highest median anti-spike (S) IgG values were seen in individuals who received BNT162b2 (2.9 AU/mL) and ChAdOx1 nCoV-19 (2.8 AU/mL) vaccines. The levels of anti-S IgG were significantly decreased after 7 months of vaccination with BNT162b2 and BBIBP-CorV. There were significant decreases in the median number of neutralizing antibodies one month and seven months after receiving BNT162b2 (from 88.5 to 75.2 4 Bioequivalent Allergen Unit per milliliter/mL), BBIBP-CorV (from 69.5 to 51.5 BAU/mL), and ChAdOx1 nCoV-19 (from 69.2 to 58.BAU/mL) vaccines. The highest percentage of T cells specific to COVID-19 vaccine was found in individuals who received BNT162b2 (88.5%). CONCLUSION: All four vaccines evaluated in this study showed effectiveness against asymptomatic COVID-19 infection, symptomatic infection, hospitalization, and death. Furthermore, BNT162b2, BBIBP-CorV, and ChAdOx1 nCoV-19 induced high levels of immunology markers within one month of vaccination.

The influence of Eruca sativa (Arugula) on pharmacokinetics of Sildenafil in rats.

OBJECTIVES: A drug like Sildenafil is commonly used for the treatment of erectile dysfunction. Eruca sativa is known as a garden plant used in folk medicine to enhance the sexual desire in males. Nevertheless, the interaction of Sildenafil and Eruca sativa was not studied. In the current study, we aimed to examine the influence of Eruca sativa on Sildenafil pharmacokinetics in rats. STUDY DESIGN: A crossover experiment with washout period of two weeks was conducted. To one group of animals, Eruca sativa was given as food and a drinking solution to rats for 12 hours before the day of the experiment. On the day of the experiment, the same group received 5 ml (50 mg/ml) orally and a half an hour later animals received 1 ml Sildenafil citrate (2.85 mg/kg) oral administrated to the study group. The other group of rats only received Sildenafil. Two-weeks later a cross-over design on the same animals was conducted. Blood samples were collected from optical vein on different time intervals, samples were analyzed using validated (HPLC-UV) method. RESULTS AND CONCLUSION: Pre-administration of Eruca sativa has increased Sildenafil Cmax from 226.72 to 345.25 ng/ml, (p<0.05). In addition, the AUC of Sildenafil has significantly increased when it was pre-administered with Eruca sativa (550.59 vs. 916.48 ng/ml*hr). Our findings suggest that co-administration of Eruca sativa with Sildenafil enhances the pharmacokinetics of Sildenafil in rats plasma.

Pomegranate and licorice juices modulate metformin pharmacokinetics in rats.

OBJECTIVES: Food or drinks may significantly alter the pharmacokinetics and pharmacodynamics of drugs which may lead to adverse events. A drug such as metformin is widely used to regulate plasma glucose level and pomegranate and licorice have been identified to help in type-2 diabetes management. However, the interactions of the latter on metformin pharmacokinetics were not studied. Therefore, we aimed here to study the impact of pomegranate and licorice on metformin pharmacokinetics in rats. METHODS: Juices were given to rats for two days and half an hour before metformin (20 mg/kg) oral administration. Blood samples, then, were collected at different time intervals, processed and analyzed using validated reliable HPLC method. Plasma profile and pharmacokinetic parameters were calculated for each group. RESULTS AND CONCLUSION: Pre-administration of pomegranate significantly reduced metformin maximum plasma concentration from 1410 to 1031 ng/ml. On the other hand, pre-administration of licorice significantly delayed metformin reaching its maximum plasma concentration. In conclusion, pre-administration of pomegranate may potentially reduce efficacy of metformin while licorice might delay metformin action. Thus, both juices should be cautiously administrated with metformin, the mainstay drug for type-2 diabetes mellitus management.

Nationality, Gender, Age, and Body Mass Index Influences on Vitamin D Concentration among Elderly Patients and Young Iraqi and Jordanian in Jordan.

Vitamin D is necessary for maintaining and regulating calcium levels; thus, insufficiency of vitamin D increases the risk of many chronic diseases. This study aimed to examine vitamin D levels among Jordanian and Iraqi volunteers and find the relation between vitamin D level and lipid profile patients. Vitamin D levels were evaluated using enzyme-linked immunosorbent assay. For young healthy group subjects, vitamin D levels were 20.60 ± 5.94 ng/mL for Jordanian and 27.59 ± 7.74 ng/mL for Iraqi. Vitamin D concentrations for young males and females were 25.82 ± 8.33 ng/mL and 21.95 ± 6.39 ng/mL, respectively. Females wearing hijab were 20.87 ± 6.45 ng/mL, while uncovered females were 23.55 ± 6.04 ng/mL. For >40 years Iraqi subjects, vitamin D level for healthy was 29.78 ± 9.49 ng/mL and 23.88 ± 7.93 ng/mL for hyperlipidemic subjects. Vitamin D levels for overweight and obese healthy groups were significantly higher (P < 0.050) than those for the hyperlipidemic patients groups. Vitamin D levels for males were significantly higher than females and were significantly higher for healthy than those hyperlipidemic Iraqi patients. These findings showed that vitamin D levels are affected by age, nationality, gender, and health statues and highlight the importance of vitamin D supplementation for groups with low levels particularly old, hijab wearing females, and hyperlipidemic groups.

Determination of loperamide in human plasma and saliva by liquid chromatography-tandem mass spectrometry.

A simple and sensitive liquid chromatography-tandem mass spectrometric method for quantification of loperamide in human plasma and saliva was developed and validated, and then successfully applied in pharmacokinetic clinical study to investigate and correlate bioavailability of Imodium(®) 2mg quartet tablet dose in both human plasma and saliva. Loperamide with labeled internal standard was extracted from its biological matrix by methanol as protein direct precipitant in single extraction step. Adequate chromatographic separation for analytes from plasma and saliva matrices was achieved using ACE C18 (50mm×2.1mm, 5µm) column, eluted by water/methanol/formic acid (30:70:0.1%, v/v), delivered isocratically at constant flow rate of 0.75ml/min. The method validation intends to investigate specificity, sensitivity, linearity, precision, accuracy, recovery, matrix effect and stability according to European guideline, and partial validation was applied on saliva, specificity, matrix effect, recovery, sensitivity, within and between day precision and accuracy. The calibration curve was linear through the range of 20-3000pg/ml in both plasma and saliva using a 50µl sample volume. The partial validation sections outcome in saliva was so close to those in plasma. The within- and between-day precisions were all below 8.7% for plasma and below 11.4% for saliva. Accuracies ranged from 94 to 105% for both matrices. In this study, 26 healthy volunteers participated in the clinical study, and 6 of gave their saliva samples in addition to plasma at the same time schedule. The pharmacokinetic parameters of Cmax, AUC0-t and AUC0-∞, Tmax and T1/2 in both plasma and saliva were calculated and correlated.

Bis(methyl-sulfon-yl)methane.

In the title compound, C3H8O4S2, the two central S-C(H2) bond lengths are almost identical [1.781 (2) and 1.789 (2) Å]. In the crystal, each mol-ecule utilizes CH2 and CH3 bonds to form weak C-H⋯O hydrogen bonds to six other mol-ecules, thus linking mol-ecules into a three-dimensional network.