Pharmacokinetics and bioavailability of fluconazole in two groups of males with human immunodeficiency virus (HIV) infection compared with those in a group of males without HIV infection

Tett, S. E.; Moore, Sarah A.; Ray, John E.

doi:10.1128/aac.39.8.1835

Cited by 43 publications

(34 citation statements)

References 20 publications

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“…A reduction in¯uconazole dose was previously suggested for people with HIV infection who are seriously ill and/or who have compromised renal function [16,18]. However, in this study, after inclusion of BW, neither lymphocyte CD4 count nor creatinine CL exhibited a signi®cant e ect on¯uconazole CL.…”

Section: Discussionmentioning

confidence: 54%

“…Although a previous study reported no e ect of BW on¯uconazole pharmacokinetics [16], in this study BW signi®cantly in¯uenced¯uconaz-ole CL and V d . In contrast to previous studies [16,18], this study included female and male patients. Since neither the covariate plots suggested any gender di erences nor the inclusion of additional parameters for gender di erences in CL and/or V d improved the ®t, a clinically relevant e ect of gender on¯uconazole pharmacokinetics can be excluded.…”

Section: Discussionmentioning

confidence: 99%

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Population pharmacokinetics of fluconazole given for secondary prevention of oropharyngeal candidiasis in HIV-positive patients

Csajka

Décosterd

Buclin

et al. 2001

Eur J Clin Pharmacol

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Objectives: To determine¯uconazole population pharmacokinetics and explore the relationships between¯uconazole average concentration and treatment e ectiveness or microbiological resistance induction during a study aimed at evaluating the e cacy, tolerability and resistance induction after secondary prevention with¯uconazole (150 mg weekly) versus placebo in human immunode®ciency virus-positive (HIV+) patients with oropharyngeal candidiasis. Methods: Population pharmacokinetic parameters of uconazole determined from 458 serum drug concentration measurements obtained over 37 months in 132 HIV+ patients not receiving highly active antiretroviral therapy. Mean estimates and variabilities were generated using non-linear regression analysis. Logistic and linear regression analyses were used to explore the relationships between the estimated average concentration of uconazole and candidiasis relapse or fungal resistance towards¯uconazole. Results: Fluconazole kinetics were best described by a one-compartment model with ®rst-order oral absorp tion from the gastrointestinal tract. The pharmacokinetics were in¯uenced only by body weight. No e ect was observed for gender, age, height or lymphocyte CD4 counts. The mean apparent population clearance was 0.79 l/h, the volume of distribution 57 l and the absorption constant (k a ) 0.93 h ±1 . Inter-occasion variability in clearance (45%) was large relative to intersubject variability (21%). Taking into account the average¯uconazole concentration or the time above the minimal inhibitory concentrations did not clinically improve the prediction of the occurrence of oropharyngeal relapse or microbiological resistance. Conclusion: The relationship between¯uconazole concentrations and preventive e ectiveness was poor. Together with the rather large inter-occasion variability in¯uconazole clearance, this suggests no role of therapeutic drug monitoring in optimising¯uconazole treatment for secondary prevention.

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Section: Discussionmentioning

confidence: 54%

Section: Discussionmentioning

confidence: 99%

Population pharmacokinetics of fluconazole given for secondary prevention of oropharyngeal candidiasis in HIV-positive patients

Csajka

Décosterd

Buclin

et al. 2001

Eur J Clin Pharmacol

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“…It has a long half-life allowing infrequent administration, is minimally (12%) bound to plasma proteins, penetrates the cerebrospinal fluid, and achieves saliva and lung concentrations that are 1.3 and 1.2 times the plasma concentrations, respectively, thereby providing higher concentrations at key areas of colonization (5)(6)(7). Additionally, in adults, fluconazole has very high (Ͼ90%) oral bioavailability (8,9).…”

mentioning

confidence: 99%

Population Pharmacokinetics of Fluconazole in Premature Infants with Birth Weights Less than 750 Grams

Momper

Capparelli

Wade

et al. 2016

Antimicrob Agents Chemother

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Fluconazole is an effective agent for prophylaxis of invasive candidiasis in premature infants. The objective of this study was to characterize the population pharmacokinetics (PK) and dosing requirements of fluconazole in infants with birth weights of <750 g. As part of a randomized clinical trial, infants born at <750 g birth weight received intravenous (i.v.) or oral fluconazole at 6 mg/kg of body weight twice weekly. Fluconazole plasma concentrations from samples obtained by either scheduled or scavenged sampling were measured using a liquid chromatography-tandem mass spectrometry assay. Population PK analysis was conducted using NONMEM 7.2. Population PK parameters were allometrically scaled by body weight. Covariates were evaluated by univariable screening followed by multivariable assessment. Fluconazole exposures were simulated in premature infants using the final PK model. A population PK model was developed from 141 infants using 604 plasma samples. Plasma fluconazole PK were best described by a one-compartment model with first-order elimination. Only serum creatinine was an independent predictor for clearance in the final model. The typical population parameter estimate for oral bioavailability in the final model was 99.5%. Scavenged samples did not bias the parameter estimates and were as informative as scheduled samples. Simulations indicated that the study dose maintained fluconazole troughs of >2,000 ng/ml in 80% of simulated infants at week 1 and 59% at week 4 of treatment. Developmental changes in fluconazole clearance are best predicted by serum creatinine in this population. A twice-weekly dose of 6 mg/kg achieves appropriate levels for prevention of invasive candidiasis in extremely premature infants.

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“…These children had a significant decrease in CL and increase in T 1/2 of theophylline. HIV infections could also lead to altered PK of levofloxacin and fluconazole (Goodwin et al, 1994;Tett et al, 1995). End-stage liver disease, which is largely the result of HCV infection, now accounts for up to 50% of deaths among persons with HIV-1 infection (Bica et al, 2001).…”

Section: Pk/pd Studiesmentioning

confidence: 99%

Altered Drug Metabolism and Transport in Pathophysiological Conditions

Gandhi¹,

Ghose²

2012

Topics on Drug Metabolism

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Pharmacokinetics and bioavailability of fluconazole in two groups of males with human immunodeficiency virus (HIV) infection compared with those in a group of males without HIV infection

Cited by 43 publications

References 20 publications

Population pharmacokinetics of fluconazole given for secondary prevention of oropharyngeal candidiasis in HIV-positive patients

Population pharmacokinetics of fluconazole given for secondary prevention of oropharyngeal candidiasis in HIV-positive patients

Population Pharmacokinetics of Fluconazole in Premature Infants with Birth Weights Less than 750 Grams

Altered Drug Metabolism and Transport in Pathophysiological Conditions

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