Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 23
Filter
2.
Clin Pharmacol Ther ; 102(1): 45-51, 2017 07.
Article in English | MEDLINE | ID: mdl-27981572

ABSTRACT

Voriconazole, a triazole antifungal agent, demonstrates wide interpatient variability in serum concentrations, due in part to variant CYP2C19 alleles. Individuals who are CYP2C19 ultrarapid metabolizers have decreased trough voriconazole concentrations, delaying achievement of target blood concentrations; whereas poor metabolizers have increased trough concentrations and are at increased risk of adverse drug events. We summarize evidence from the literature supporting this association and provide therapeutic recommendations for the use of voriconazole for treatment based on CYP2C19 genotype (updates at https://cpicpgx.org/guidelines/ and www.pharmgkb.org).


Subject(s)
Cytochrome P-450 CYP2C19/genetics , Drug-Related Side Effects and Adverse Reactions , Genotyping Techniques/methods , Metabolic Clearance Rate/physiology , Voriconazole , Antifungal Agents/pharmacokinetics , Antifungal Agents/therapeutic use , Dose-Response Relationship, Drug , Drug-Related Side Effects and Adverse Reactions/metabolism , Drug-Related Side Effects and Adverse Reactions/prevention & control , Humans , Patient Selection , Pharmacogenomic Variants/genetics , Risk Assessment/methods , Voriconazole/pharmacokinetics , Voriconazole/therapeutic use
3.
J Clin Pharm Ther ; 42(1): 75-79, 2017 Feb.
Article in English | MEDLINE | ID: mdl-27982447

ABSTRACT

WHAT IS KNOWN AND OBJECTIVE: Posaconazole is an extended-spectrum triazole antifungal with activity against a variety of clinically significant yeasts and moulds. Posaconazole is not currently approved by the U.S. Food and Drug Administration for use in children younger than 13 years of age. Our primary objective was to describe the dosing and observed trough concentrations with posaconazole oral suspension in paediatric patients at the National Institutes of Health Clinical Center (Bethesda, MD). METHODS: This retrospective single-centre study reviewed paediatric patients younger than 13 years of age initiated on posaconazole oral suspension. Patients were included if they were initiated on posaconazole for prophylaxis or treatment for fungal infections from September 2006 through March 2013 with at least one trough concentration collected after at least 7 days of therapy. RESULTS AND DISCUSSION: A total of 20 male patients were included, of whom 15 (75%) had chronic granulomatous disease. The median age of patients was 6·5 years (range: 2·8-10·7). A total of 79 posaconazole trough concentrations were measured in patients receiving posaconazole as prophylaxis (n = 8) or treatment (n = 12). Posaconazole dose referenced to total body weight ranged from 10·0 to 49·2 mg/kg/day. Posaconazole trough concentrations ranged from undetectable (<50 ng/mL) up to 3620 ng/mL and were ≥500, ≥700 and ≥1250 ng/mL in 95%, 60% and 25% of patients, respectively. WHAT IS NEW AND CONCLUSIONS: Patients younger than 13 years of age had highly variable trough concentrations, and recommendations for the appropriate dosing of posaconazole oral suspension remain challenging. Until studies are conducted to determine the appropriate dosing of posaconazole in this patient population, therapeutic drug monitoring should be considered to ensure adequate posaconazole exposure.


Subject(s)
Antifungal Agents/administration & dosage , Mycoses/drug therapy , Suspensions/administration & dosage , Triazoles/administration & dosage , Administration, Oral , Child , Child, Preschool , Drug Monitoring/methods , Humans , Male , Retrospective Studies
4.
Int J Clin Pharmacol Ther ; 48(12): 847-53, 2010 Dec.
Article in English | MEDLINE | ID: mdl-21084040

ABSTRACT

UNLABELLED: A previous study reported a 2- and 3-timepoint limited sampling strategy (LSS) model accurately predicted oral midazolam area under the concentration time curve (AUC), and thus cytochrome P450 (CYP) 3A activity. OBJECTIVE: This study evaluated whether the LSS models predict midazolam AUC during CYP3A baseline, inhibition and induction/activation. MATERIALS AND METHODS: Plasma midazolam concentrations from 106 healthy adults from 6 published studies were obtained where oral midazolam was co-administered alone or with ketoconazole, double-strength grapefruit juice, Ginkgo biloba extract, pleconaril, or rifampin. Observed and predicted midazolam AUCs were determined. Bias and precision of the LSS models were determined. RESULTS: Contrasting results were observed for the 2- and 3-timepoint LSS models in accurately predicting midazolam AUC during baseline CYP3A conditions. With the exception of 1 study (single dose, double-strength grapefruit juice), the 2- and 3-timepoint LSS models did not accurately predict midazolam AUC during conditions of CYP3A inhibition and induction/activation. CONCLUSION: The previously reported 2- and 3-timepoint oral midazolam LSS models are not applicable to the evaluated conditions of CYP3A baseline, inhibition, and induction/ activation.


Subject(s)
Cytochrome P-450 CYP3A/physiology , Midazolam/pharmacokinetics , Administration, Oral , Area Under Curve , Cytochrome P-450 CYP3A Inhibitors , Enzyme Activation , Humans
5.
Am J Transplant ; 8(6): 1297-302, 2008 Jun.
Article in English | MEDLINE | ID: mdl-18444933

ABSTRACT

Valganciclovir is commonly used for cytomegalovirus (CMV) prophylaxis in renal transplant patients. A fixed dose of 900 mg daily is typically recommended, however, there has never been a formal pharmacokinetic study comparing various doses in renal transplant patients. We therefore compared the pharmacokinetic characteristics of intravenous ganciclovir (IV GCV) and oral ganciclovir (GCV) with two different doses of valganciclovir (VGCV) in an open-label crossover study. Ten adult kidney recipients participated in a four-phase crossover treatment schedule of IV GCV (2.5 mg/kg every 12 h), VGCV (900 mg daily), VGCV (450 mg daily) and oral GCV (1000 mg Q8 H). IV GCV and oral VGCV 900 mg daily achieved similar values for AUC(0-24) (median 60.63 vs. 62.86 microg/h/mL). Oral VGCV 450 mg achieved comparable AUC(0-24) values as oral GCV 1000 mg Q8 H (median AUC(0-24) 35.9 vs. 29.04 microg/h/mL). Oral VGCV 900 mg daily provided systemic GCV exposure similar to IV GCV and confirms PV 16 000 study results. Further, VGCV 450 mg daily provided comparable systemic exposure versus oral GCV. Due to its favorable pharmacokinetic profile, data herein suggest that VGCV can be used in the early post-kidney transplant period, and that 450 mg daily provides ample drug exposure for effective CMV prophylaxis in kidney transplant patients.


Subject(s)
Antiviral Agents/pharmacokinetics , Cytomegalovirus Infections/prevention & control , Ganciclovir/analogs & derivatives , Kidney Transplantation , Adult , Antiviral Agents/administration & dosage , Cross-Over Studies , Cytomegalovirus Infections/etiology , Dose-Response Relationship, Drug , Female , Ganciclovir/administration & dosage , Ganciclovir/pharmacokinetics , Humans , Kidney Transplantation/adverse effects , Male , Middle Aged , Valganciclovir
6.
HIV Med ; 8(2): 86-91, 2007 Mar.
Article in English | MEDLINE | ID: mdl-17352764

ABSTRACT

OBJECTIVES: Polymorphisms in the cytochrome P450 (CYP) 2B6 gene have been shown to influence nevirapine plasma concentrations in HIV-infected European Caucasians. Although nevirapine is used extensively in Africa, the influence of CYP2B6 genotype on nevirapine exposure has not been assessed in this population. We aimed to determine the influence of CYP2B6 genotype at position 516 on nevirapine trough concentrations in HIV-infected patients in Kampala, Uganda. Additional polymorphisms in the CYP and multidrug resistance protein-1 (MDR-1) genes were also assessed for their impact on nevirapine concentrations. METHODS: The following genotypes were determined in all subjects using polymerase chain reaction-restriction fragment length polymorphism: CYP2B6 G516T, MDR-1 C3435T and G2677T, CYP3A4(*)1B and CYP3A5(*)3. Nevirapine plasma concentrations were determined using high-performance liquid chromatography in 23 HIV-infected patients who were generally healthy and had been taking nevirapine 200 mg twice daily for at least 14 days. Analysis of variance with post hoc testing was used to compare nevirapine concentrations among CYP2B6 genotype groups. RESULTS: The median nevirapine trough concentration in individuals homozygous for the variant allele (TT) was 7607 ng/mL vs 4181 and 5559 ng/mL for GG and GT individuals, respectively (GG vs TT median ratio=1.82; P=0.011). The mean ratio for TT vs GG individuals (95% confidence interval) was 1.51 (1.18, 1.84). No associations were observed between the other polymorphisms studied and nevirapine concentrations. CONCLUSIONS: CYP2B6 G516T significantly influenced nevirapine trough concentrations in HIV-infected patients in Uganda. Additional studies in larger patient populations are necessary to further define the potential clinical impact of these preliminary findings.


Subject(s)
Aryl Hydrocarbon Hydroxylases/genetics , HIV Infections/blood , Nevirapine/blood , Oxidoreductases, N-Demethylating/genetics , Reverse Transcriptase Inhibitors/blood , Adult , Cohort Studies , Cytochrome P-450 CYP2B6 , Female , Genotype , HIV Infections/drug therapy , HIV Infections/epidemiology , Humans , Male , Middle Aged , Nevirapine/therapeutic use , Pilot Projects , Polymorphism, Genetic , Reverse Transcriptase Inhibitors/therapeutic use , Sex Distribution , Uganda/epidemiology
7.
Pharmacology ; 67(4): 195-201, 2003 Apr.
Article in English | MEDLINE | ID: mdl-12595750

ABSTRACT

A potential cytokine-drug interaction between interleukin 6 (IL-6) and itraconazole (ITZ) was studied using human hepatocytes in primary culture. Cultures from 5 adult males (mean age 42 +/- 15 years) who had not received any medicines known to interact with CYP3A4 were studied. Cultures were exposed to ITZ 500 ng/ml, and the effects of 120 microg/ml cimetidine, 50 ng/ml human IL-6, or IL-6 plus IL-6 receptor antagonist were analyzed for 2, 4, 8, and 12 h. Intracellular ITZ and hydroxyitraconazole concentrations were measured using HPLC and normalized to total cellular protein. Mean intracellular concentrations between groups were compared using one-way Anova (f test; p < 0.10) and corresponding Bonferroni versus control test for multiple comparisons (p < 0.02). Mean intracellular ITZ concentrations between the groups were similar at all time points. Human hepatocytes in primary culture can metabolize ITZ. However, IL-6 did not inhibit hydroxyitraconazole formation, but it may inhibit its subsequent metabolism.


Subject(s)
Hepatocytes/drug effects , Interleukin-6/pharmacology , Itraconazole/analogs & derivatives , Itraconazole/metabolism , Itraconazole/pharmacology , Liver/drug effects , Adult , Cells, Cultured , Cimetidine/pharmacology , Cytochrome P-450 Enzyme Inhibitors , Cytochrome P-450 Enzyme System/metabolism , Drug Interactions , Enzyme Inhibitors/pharmacology , Hepatocytes/metabolism , Humans , Liver/cytology , Liver/metabolism , Male , Middle Aged , Receptors, Interleukin-6/antagonists & inhibitors
8.
J Clin Pharmacol ; 41(10): 1059-63, 2001 Oct.
Article in English | MEDLINE | ID: mdl-11583473

ABSTRACT

The Seville orange extract Citrus aurantium contains m-synephrine (phenylephrine) and octopamine; it causes cardiac disturbances in animals and is used by humans for weight loss. Juice from the orange (Seville orange juice [SOJ]) is used to "knock out" intestinal cytochrome P450 (CYP) 3A4 in bioavailability studies. The purpose of this study was to determine synephrine and octopamine concentrations in SOJ and SOJ's cardiovascular effects in normotensive humans. Subjects consumed 8 ounces of SOJ and water in crossover fashion followed by a repeat ingestion 8 hours later. Hemodynamic (heart rate; systolic, diastolic, and mean arterial pressure) measurements followed. Synephrine and octopamine were determined by high-performance liquid chromatography. Hemodynamics did not differ significantly between water and SOJ groups. Mean synephrine concentration of SOJ samples was 56.9 +/- 0.52 microg/ml; octopamine was not detected. SOJ ingestion by normotensive subjects is expected to be safe. Individuals with severe hypertension, tachyarrhythmias, and narrow-angle glaucoma and monoamine oxidase inhibitor recipients should avoid SOJ consumption. Persons taking decongestant-containing cold preparations should also refrain from SOJ intake.


Subject(s)
Beverages/analysis , Cardiovascular System/drug effects , Citrus/chemistry , Synephrine/analysis , Synephrine/pharmacology , Vasoconstrictor Agents/analysis , Vasoconstrictor Agents/pharmacology , Adult , Analysis of Variance , Cross-Over Studies , Female , Hemodynamics/drug effects , Hemodynamics/physiology , Humans , Male , Plant Extracts/analysis , Plant Extracts/pharmacology , Synephrine/chemistry , Vasoconstrictor Agents/chemistry
9.
Int J Clin Pharmacol Ther ; 39(9): 400-5, 2001 Sep.
Article in English | MEDLINE | ID: mdl-11563687

ABSTRACT

Ritonavir is an HIV-1 protease inhibitor that is often used to improve the systemic availability of concurrently administered protease inhibitors by impairing their metabolism through cytochrome P450 (CYP) 3A4. Pharmacodynamic relationships between plasma ritonavir concentrations and efficacy and toxicity have also been described. To date, published high-performance liquid chromatographic (HPLC) methods for the determination of ritonavir in human plasma are often complex, requiring the use of a buffered mobile phase that contains amine-modifiers (i.e. diethylamine, triethylamine). In the method herein, ritonavir was precipitated with acetonitrile plus barium hydroxide and zinc sulphate. Chromatographic separation was accomplished using a C-18 base-deactivated (250 x 4.6 mm I.D., 5 atm particle size) analytic column with a mobile phase composed of acetonitrile:water (52:48, v/v). Quantification was performed at 239 nm. Calibration curves were linear from 0.5-25 microg/ml (R2 > 0.999); percent errors, as a measure of accuracy, were < 12.7%. Intra- and inter-assay relative standard deviations (RSD) were below 12.8%. This method provides a rapid and simple means for the accurate and precise analysis of ritonavir in human plasma. Furthermore, the assay requires neither the use of a buffered mobile phase adjusted to a specific pH, nor the addition of amine modifiers. This method has been successfully used to determine plasma ritonavir concentrations in drug interaction studies.


Subject(s)
Chromatography, High Pressure Liquid/standards , HIV Protease Inhibitors/pharmacokinetics , Plasma/metabolism , Ritonavir/pharmacokinetics , HIV Protease Inhibitors/blood , Humans , Reference Values , Ritonavir/blood , Sensitivity and Specificity
10.
Clin Infect Dis ; 31(6): 1512-4, 2000 Dec.
Article in English | MEDLINE | ID: mdl-11096026

ABSTRACT

The purpose of this retrospective study was to assess cross-hypersensitivity between imipenem/cilastatin and penicillin in patients with reported penicillin allergies. Medical records of febrile neutropenic, penicillin-allergic bone marrow transplant recipients who received imipenem/cilastatin treatment were retrospectively reviewed. The findings of this study indicate the incidence of cross-reactivity between imipenem/cilastatin and penicillin among patients with a history of penicillin allergy may be lower than previously reported.


Subject(s)
Bone Marrow Transplantation , Cilastatin/adverse effects , Drug Hypersensitivity/epidemiology , Drug Hypersensitivity/etiology , Imipenem/adverse effects , Penicillins/adverse effects , Adult , Aged , Cilastatin, Imipenem Drug Combination , Cross Reactions , Drug Combinations , Fever , Humans , Incidence , Middle Aged , Neutropenia , Retrospective Studies
11.
Pharmacotherapy ; 20(9): 1066-71, 2000 Sep.
Article in English | MEDLINE | ID: mdl-10999499

ABSTRACT

STUDY OBJECTIVE: To assess the efficacy and safety of HMG-CoA reductase inhibitors (statins) in patients with human immunodeficiency virus (HIV) infection and hyperlipidemia. DESIGN: Retrospective analysis. SETTING: HIV clinic. PATIENTS: Twenty-six HIV-infected patients with hyperlipidemia. INTERVENTION: Five patients received pravastatin, 13 lovastatin, 10 simvastatin, and 2 atorvastatin (total 30 courses). MEASUREMENTS AND MAIN RESULTS: Reductions in cholesterol and triglycetides were used to assess efficacy; creatine kinase (CK), liver enzymes, and myalgia were markers of statin toxicity. After a median of 8.2 and 7.2 months of treatment, the agents collectively reduced median baseline total cholesterol 27% (354 to 263 mg/dl) and triglycerides 15% (513 to 438 mg/dl), respectively. Two patients, one with marked CK elevations, experienced myalgias with lovastatin, and two experienced transaminase elevations 3 or more times the upper limit of normal. CONCLUSION: Statins are effective in reducing total cholesterol and triglycerides in HIV-infected patients, although lipid levels infrequently return to normal. Lovastatin should be avoided in patients receiving concomitant drugs that may potentiate skeletal muscle toxicity with this agent.


Subject(s)
Cholesterol/blood , HIV Infections/complications , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Hyperlipidemias/drug therapy , Triglycerides/blood , Adult , Aged , Female , HIV Infections/blood , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/adverse effects , Hyperlipidemias/blood , Male , Middle Aged , Muscle, Skeletal/drug effects , Muscle, Skeletal/metabolism , Retrospective Studies , Transaminases/drug effects , Transaminases/metabolism
12.
Infect Control Hosp Epidemiol ; 21(9): 597-9, 2000 Sep.
Article in English | MEDLINE | ID: mdl-11001264

ABSTRACT

OBJECTIVE: To identify risk factors associated with an outbreak of gram-negative bacteremia (GNB). SETTING: A university hospital. PATIENTS: Hematology-oncology outpatients. DESIGN: Retrospective case-control study. RESULTS: Thirty-eight patients developed GNB; 13 patients experienced more than one episode, and eight blood cultures grew more than one gram-negative organism. The most frequently isolated organisms were Stenotrophomonas maltophilia, Klebsiella pneumoniae, Acinetobacter baumannii, and Acinetobacter johnsonii. When the GNB patients (cases) were compared with randomly selected hematology-oncology patients (controls), central venous catheter (CVC) self-care (71% vs 39%; P=.02), and duration of recent hospital stay (median, 15 vs 4 days; P=.01) were identified as risk factors. In a logistic regression model, duration of recent hospital stay was the only risk factor significantly associated with GNB (odds ratio, 1.05; 95% confidence interval, 1.01-1.08; P<.02). CONCLUSIONS: Hematology-oncology patients providing their own CVC care who have recently been hospitalized for more than 2 weeks may be at increased risk of GNB. CVCs should be protected from possible environmental contamination in hematologyoncology patients. Patients providing their own CVC care should undergo continued rigorous education regarding proper CVC care.


Subject(s)
Bacteremia/epidemiology , Cross Infection/epidemiology , Disease Outbreaks , Gram-Negative Bacterial Infections/epidemiology , Neoplasms/therapy , Oncology Service, Hospital , Adult , Aged , Bacteremia/etiology , Case-Control Studies , Female , Gram-Negative Bacterial Infections/etiology , Hospital Departments , Hospitals, University , Humans , Male , Middle Aged , Retrospective Studies , Risk Factors
13.
Scand J Infect Dis ; 32(2): 111-23, 2000.
Article in English | MEDLINE | ID: mdl-10826894

ABSTRACT

Despite potent antiretroviral activity, the HIV-1 protease inhibitors have recently been associated with abnormal serum lipoprotein concentrations. The purpose of this review is to describe serum lipid abnormalities related to protease inhibitor use. A MEDLINE search up to June 1, 1999, and abstracts from recent scientific meetings were primary data sources. Lipid disturbances in HIV-infected patients receiving protease inhibitors generally consist of elevated triglycerides and total cholesterol levels; HDL cholesterol is often reduced. The pathophysiological mechanism by which the protease inhibitors induce these lipid abnormalities has been hypothesized, but is unknown. Cases of pancreatitis and coronary heart disease have been described in hyperlipidemic patients receiving protease inhibitors. Treatment of protease inhibitor-related hyperlipidemia is unknown. Exchanging the offending protease inhibitor for nevirapine may be helpful in certain patients. Atorvastatin in combination with gemfibrozil has been used with limited success in a small number of individuals.


Subject(s)
HIV Infections/drug therapy , HIV Protease Inhibitors/adverse effects , Hyperlipidemias/chemically induced , Cholesterol, HDL/blood , Female , Humans , Hypercholesterolemia/chemically induced , Hyperlipidemias/epidemiology , Hyperlipidemias/physiopathology , Male , Prevalence , Risk Factors , Time Factors , Triglycerides/blood
14.
Am J Health Syst Pharm ; 57(4): 376-86; quiz 387-9, 2000 Feb 15.
Article in English | MEDLINE | ID: mdl-10714976

ABSTRACT

The epidemiology, clinical features, and drug treatment of depression in HIV-infected patients are discussed. The lifetime prevalence of depression in patients infected with HIV has been estimated at 22-45%. The signs and symptoms of depression are similar in HIV-infected and noninfected patients, but patients with HIV infection may more frequently have sleep and appetite disturbances. Diagnosis should focus on affective or cognitive depression symptoms that reflect mood state alone. Patients with a history of depression, homosexual men, women, and i.v. drug abusers are among HIV-infected individuals who may be at increased risk for depression. Depression may alter the course of HIV infection by impairing immune function or influencing behavior. Depression my contribute to nonadherence to therapy. Antidepressant therapy is effective in most HIV-positive patients with major depression. Tricyclic antidepressants (TCAs) have produced response rates as high as 89%, but their usefulness has been limited by adverse effects. Selective serotonin-reuptake inhibitors and other non-TCAs have also demonstrated efficacy and are generally better tolerated. Psychostimulants have improved mood, cognition, and energy level, and androgens have been used for their anabolic effects. The systemic concentrations of antidepressants may be altered by coadministered drugs that affect their cytochrome P-450 isoenzyme-mediated metabolism; in turn, the metabolism and toxicity of certain antiretrovirals may be affected by antidepressants. Guidelines on the treatment of depression in the general population may be applied to patients with HIV infection. Depressive disorders are prevalent among patients with HIV infection but often respond to a variety of treatments.


Subject(s)
Depressive Disorder/etiology , HIV Infections/psychology , Antidepressive Agents/metabolism , Antidepressive Agents/therapeutic use , Clinical Trials as Topic , Depressive Disorder/drug therapy , Depressive Disorder/epidemiology , HIV Infections/complications , HIV Infections/drug therapy , HIV Infections/epidemiology , Humans , Prevalence
15.
Am J Health Syst Pharm ; 56(19): 1929-35; quiz 1936, 1999 Oct 01.
Article in English | MEDLINE | ID: mdl-10554910

ABSTRACT

Recent findings on the epidemiology and treatment of funguria are reviewed. Funguria, or candiduria, is a common nosocomial condition and may develop as early as the first two weeks of hospitalization. Risk factors include antibacterial therapy, an indwelling urinary catheter, urologic procedures, female sex, diabetes, and immunosuppressive therapy. Candida albicans is the species most commonly isolated from the urine of infected patients. Spontaneous resolution of funguria is relatively infrequent. Furthermore, although nonpharmacologic measures, such as removing unnecessary antibacterials and changing or removing indwelling urinary catheters, may be beneficial, they are often inadequate without additional, pharmacologic therapy. The most serious complication of untreated asymptomatic funguria is candidemia. Bladder irrigations with amphotericin B have been the standard of therapy for many years; recently, the optimal concentration and method of irrigation (continuous versus intermittent) have been debated. Studies indicate that intravesical amphotericin B and oral fluconazole therapy are each effective in clearing funguria. Intravesical amphotericin B appears to act more rapidly; however, the effect of systemic fluconazole therapy often persists longer than that of amphotericin B irrigation, and oral therapy is more convenient and less expensive. Oral fluconazole appears to have a more delayed but more lasting effect on funguria than amphotericin B bladder irrigation. Studies are needed to determine whether intravesical amphotericin B still has a role in the treatment of funguria and to refine strategies involving fluconazole.


Subject(s)
Amphotericin B/therapeutic use , Antifungal Agents/therapeutic use , Candidiasis/drug therapy , Cross Infection/drug therapy , Cross Infection/etiology , Fluconazole/therapeutic use , Urinary Catheterization/adverse effects , Amphotericin B/administration & dosage , Antifungal Agents/administration & dosage , Candidiasis/epidemiology , Candidiasis/etiology , Candidiasis/urine , Cross Infection/epidemiology , Female , Fluconazole/administration & dosage , Humans , Male , Sex Factors , Urinary Tract Infections/drug therapy , Urinary Tract Infections/epidemiology , Urinary Tract Infections/etiology
16.
Ther Drug Monit ; 21(3): 304-9, 1999 Jun.
Article in English | MEDLINE | ID: mdl-10365642

ABSTRACT

The systemic availability of itraconazole capsules may be reduced secondary to elevated gastric pH and possibly by presystemic intestinal metabolism via CYP3A4. Grapefruit juice is acidic and an inhibitor of intestinal CYP3A4. To determine the effect of grapefruit juice on the systemic availability of itraconazole capsules, serum itraconazole and hydroxy-itraconazole concentrations were determined in eleven healthy volunteers studied in a randomized, two-way crossover design. Concurrent grapefruit juice resulted in a 43% decrease in the mean itraconazole AUC0-48 (2507 ng x hr/mL versus 1434 ng x hr/mL, p = 0.046) and a 47% decrease in the mean hydroxy-itraconazole AUC0-72 (7264 ng x hr/mL versus 3880 ng x hr/mL, p = 0.025). Grapefruit juice also significantly increased the mean itraconazole Tmax (5.5 versus 4 hours). We conclude that concomitant grapefruit juice does not enhance the systemic availability of itraconazole capsules, but rather appears to impair itraconazole absorption. Therefore, concomitant grapefruit juice will not likely be useful in improving the oral availability of itraconazole capsules.


Subject(s)
Antifungal Agents/pharmacokinetics , Citrus , Itraconazole/pharmacokinetics , Adult , Biological Availability , Capsules , Cross-Over Studies , Cytochrome P-450 CYP3A , Cytochrome P-450 Enzyme System/metabolism , Female , Humans , Hydrogen-Ion Concentration , Intestinal Absorption , Male , Mixed Function Oxygenases/metabolism , Reference Values
18.
Pharmacotherapy ; 18(3): 549-64, 1998.
Article in English | MEDLINE | ID: mdl-9620106

ABSTRACT

We reviewed the effect of systemic, intranasal, and lipid formulations of amphotericin B, fluconazole, itraconazole for antifungal prophylaxis. Specifically we reviewed the effect of antifungal prophylaxis on the development of fungal colonization, frequency of superficial and invasive mycosis, and overall mortality and that due to invasive mycoses in bone marrow transplantation recipients. A MEDLINE search was conducted to identify literature describing the risk factors, epidemiology, and chemoprophylaxis of invasive mycosis in these patients. Preliminary data published as abstracts at national infectious diseases and hematology conferences within the last 5 years were included. Antifungal prophylaxis reduces fungal colonization and superficial infection. The ability of antifungal prophylaxis to prevent systemic infection or reduce the need for empiric amphotericin B depends on specific variables. Ultimately, antifungal prophylaxis has no affect on overall mortality, and very little impact on mortality attributed to fungi.


Subject(s)
Antifungal Agents/therapeutic use , Aspergillosis/prevention & control , Bone Marrow Transplantation , Candidiasis/prevention & control , Postoperative Complications/prevention & control , Amphotericin B/administration & dosage , Amphotericin B/therapeutic use , Antifungal Agents/administration & dosage , Aspergillosis/microbiology , Aspergillosis/mortality , Candidiasis/microbiology , Candidiasis/mortality , Fluconazole/administration & dosage , Fluconazole/therapeutic use , Humans , Itraconazole/administration & dosage , Itraconazole/therapeutic use , MEDLINE , Postoperative Complications/microbiology , Postoperative Complications/mortality , Randomized Controlled Trials as Topic , Risk Factors
19.
Ther Drug Monit ; 20(3): 261-5, 1998 Jun.
Article in English | MEDLINE | ID: mdl-9631922

ABSTRACT

The authors describe the therapeutic drug monitoring of vancomycin in a man who is morbidly obese. Because serum vancomycin concentration (SVC) monitoring continues to be deemphasized, nomogram use will likely increase. However, vancomycin dosing nomograms have not been studied in patients who are morbidly obese. Furthermore, in nomograms that incorporate body weight, it is unclear whether ideal or total body weight (IBW and TBW, respectively) should be used to dose the morbidly obese. Therefore, the authors retrospectively evaluated four nomograms (Moellering, Matzke, Lake-Peterson, and Rodvold) and an individualized method in the simulated vancomycin dosing of their patient. Total body weight was more accurate than IBW in selecting a vancomycin dose when using the individualized method and in all nomograms except the Matzke nomogram. The Rodvold nomogram and the individualized method yielded the most appropriate doses. All nomograms suggested dosing intervals that were unacceptably short; the individualized method suggested an appropriately longer interval. Thus, if nomograms or the individualized method are used to empirically dose vancomycin, TBW--not IBW--should be used. Because these nomograms yielded inappropriately short dosing intervals in the patient, it is likely that patients who are morbidly obese represent a unique population in which at least one set of SVCs are necessary to select an appropriate dosing regimen.


Subject(s)
Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/pharmacokinetics , Drug Monitoring/standards , Obesity, Morbid/blood , Vancomycin/administration & dosage , Vancomycin/pharmacokinetics , Anti-Bacterial Agents/blood , Body Weight , Humans , Male , Middle Aged , Retrospective Studies , Vancomycin/blood
SELECTION OF CITATIONS
SEARCH DETAIL
...