scholarly journals Population Pharmacokinetics of Lamivudine in Human Immunodeficiency Virus-Exposed and -Infected Infants

2007 ◽  
Vol 51 (12) ◽  
pp. 4297-4302 ◽  
Author(s):  
Adriana H. Tremoulet ◽  
Edmund V. Capparelli ◽  
Parul Patel ◽  
Edward P. Acosta ◽  
Katherine Luzuriaga ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Population Pharmacokinetic Analysis ◽  
Pharmacokinetic Analysis ◽  
Population Pharmacokinetic ◽  
Individual Subject ◽  
Final Model ◽  
Interoccasion Variability ◽  
Immunodeficiency Virus ◽  
Hiv Exposed ◽  
The Individual

ABSTRACT This study aimed to determine lamivudine disposition in infants and to construct an appropriate dose adjustment for age, given the widespread use of lamivudine for both the prevention of mother-to-child transmission of human immunodeficiency virus (HIV) and the treatment of HIV-infected infants. Using a pooled-population approach, the pharmacokinetics of lamivudine in HIV-exposed or -infected infants from four Pediatric AIDS Clinical Trials Group studies were assessed. Ninety-nine infants provided 559 plasma samples for measurement of lamivudine concentrations. All infants received combination antiretroviral therapy including lamivudine dosed at 2 mg/kg of body weight every 12 h (q12h) for the first 4 to 6 weeks of life and at 4 mg/kg q12h thereafter. Lamivudine's apparent clearance was 0.25 liter/h/kg at birth, doubling by 28 days. In the final model, age and weight were the only significant covariates for lamivudine clearance. While lamivudine is predominantly renally eliminated, the serum creatinine level was not an independent covariate in the final model, possibly because it was confounded by age. Inclusion of interoccasion variability for bioavailability improved the individual subject clearance prediction over the age range studies. Simulations based on the final model predicted that by the age of 4 weeks, 90% of infant lamivudine concentrations with the standard 2 mg/kg dose of lamivudine fell below the adult median concentration. This population pharmacokinetic analysis affirms that adjusting the dose of lamivudine from 2 mg/kg to 4 mg/kg q12 h at the age of 4 weeks for infants with normal maturation of renal function will provide optimal lamivudine exposure, potentially contributing to more successful therapy.

scholarly journals Pyrimethamine pharmacokinetics in human immunodeficiency virus-positive patients seropositive for Toxoplasma gondii.

1996 ◽  
Vol 40 (6) ◽  
pp. 1360-1365 ◽  
Author(s):  
J M Jacobson ◽  
M Davidian ◽  
P M Rainey ◽  
R Hafner ◽  
R H Raasch ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Toxoplasma Gondii ◽  
Drug Users ◽  
Compartment Model ◽  
Population Pharmacokinetic Analysis ◽  
Pharmacokinetic Analysis ◽  
Pharmacokinetic Parameters ◽  
Population Pharmacokinetic ◽  
Time Curve ◽  
Immunodeficiency Virus

Pyrimethamine pharmacokinetics were studied in 11 human immunodeficiency virus (HIV)-positive patients who were seropositive for exposure to Toxoplasma gondii and were taking zidovudine (AIDS Clinical Trials Group Protocol 102). Pyrimethamine was administered at 50 mg daily for 3 weeks to achieve steady state, and pharmacokinetic profiles were determined after administration of the last dose. Noncompartmental and compartmental analyses were performed. Population pharmacokinetic analysis assuming a one-compartment model yielded the following estimates: area under the 24-h concentration-time curve, 42.7 +/- 12.3 micrograms.h/ml; halflife, 139 +/- 34 h; clearance, 1.28 +/- 0.41 liters/h; volume of distribution, 246 +/- 641; and absorption rate constant, 1.5 +/- 1.3 liters/h. These values are similar to those seen in subjects without HIV infection. Pyrimethamine pharmacokinetics did not differ significantly in those subjects who were intravenous drug users. Adverse effects were noted in 73% of those initially enrolled in this study, leading to discontinuation for 38%. No association was noted between pyrimethamine levels and the incidence of adverse events. No significant differences were seen in zidovudine pharmacokinetic parameters obtained from studies performed before and during treatment with pyrimethamine. In summary, pyrimethamine exhibited pharmacokinetics in HIV-infected patients that were similar to those in non-HIV-infected subjects and it did not alter the pharmacokinetics of zidovudine in these patients.

scholarly journals A Population Pharmacokinetic Analysis of Nelfinavir Mesylate in Human Immunodeficiency Virus-Infected Patients Enrolled in a Phase III Clinical Trial

2000 ◽  
Vol 44 (7) ◽  
pp. 1832-1837 ◽  
Author(s):  
Kimberley A. Jackson ◽  
Sara E. Rosenbaum ◽  
Bradley M. Kerr ◽  
Yazdi K. Pithavala ◽  
Geoffrey Yuen ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Human Immunodeficiency Virus ◽  
Population Pharmacokinetic Analysis ◽  
Phase Iii ◽  
Baseline Viral Load ◽  
Accurate Estimation ◽  
Pharmacokinetic Analysis ◽  
Population Pharmacokinetic ◽  
Phase Iii Clinical Trial ◽  
Immunodeficiency Virus

ABSTRACT A population pharmacokinetic analysis was conducted on nelfinavir in patients infected with human immunodeficiency virus (HIV) who were enrolled in a phase III clinical trial. The data consisted of 509 plasma concentrations from 174 patients who received nelfinavir at a dose of 500 or 750 mg three times a day. The analysis was performed using nonlinear mixed-effect modeling as implemented in NONMEM (version 4.0; double precision). A one-compartment model with first-order absorption best described the data. The timing and small number of early postdose blood levels did not allow accurate estimation of volume of distribution (V/F) and the absorption rate constant (ka ). As a result, two models were used to analyze the data: model 1, in which oral clearance (CL/F),V/F, and ka were estimated, and model 2, in which V/F and ka were fixed to known values and only CL/F was estimated. Estimates of CL/F ranged from 41.9 to 45.1 liters/h, values in close agreement with previous studies. Neither body weight, age, sex, race, dose level, baseline viral load, metabolite-to-parent drug plasma concentration ratio, history of liver disease, nor elevated results of liver function tests appeared to be significant covariates for clearance. The only significant covariate-parameter relationship was concomitant use of fluconazole on CL/F, which was associated with a modest reduction in interindividual variability of CL/F. Patients who received concomitant therapy with fluconazole had a statistically significant reduction in nelfinavir CL/F of 26 to 30%. Since serious dose-limiting toxicity and concentration-related toxicities are not apparent for nelfinavir, this effect of fluconazole is unlikely to be of clinical significance.

scholarly journals Population Pharmacokinetics of Abacavir in Plasma and Cerebrospinal Fluid

2005 ◽  
Vol 49 (6) ◽  
pp. 2504-2506 ◽  
Author(s):  
Edmund V. Capparelli ◽  
Scott L. Letendre ◽  
Ronald J. Ellis ◽  
Parul Patel ◽  
Diane Holland ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Cerebrospinal Fluid ◽  
Population Pharmacokinetics ◽  
Virus Replication ◽  
Dose Interval ◽  
Population Pharmacokinetic Analysis ◽  
Pharmacokinetic Analysis ◽  
Human Immunodeficiency Virus Replication ◽  
Population Pharmacokinetic ◽  
Immunodeficiency Virus

ABSTRACT The distribution of abacavir into the cerebrospinal fluid (CSF) was assessed by use of a population pharmacokinetic analysis. Plasma and CSF abacavir concentrations in 54 subjects were determined. The abacavir CSF/plasma ratio averaged 36% and increased throughout the dose interval. Abacavir penetrates into the CSF in adequate concentrations to inhibit local human immunodeficiency virus replication.

scholarly journals Dose evaluation of lamivudine in human immunodeficiency virus-infected children aged 5 months to 18 years based on a population pharmacokinetic analysis

2017 ◽  
Vol 83 (6) ◽  
pp. 1287-1297 ◽  
Author(s):  
Esther J. H. Janssen ◽  
Diane E. T. Bastiaans ◽  
Pyry A. J. Välitalo ◽  
Annemarie M. C. van Rossum ◽  
Evelyne Jacqz-Aigrain ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Population Pharmacokinetic Analysis ◽  
Pharmacokinetic Analysis ◽  
Population Pharmacokinetic ◽  
Dose Evaluation ◽  
Immunodeficiency Virus

scholarly journals Cytochrome P450 3A Inhibition by Atazanavir and Ritonavir, but Not Demography or Drug Formulation, Influences Saquinavir Population Pharmacokinetics in Human Immunodeficiency Virus Type 1-Infected Adults

2009 ◽  
Vol 53 (8) ◽  
pp. 3524-3527 ◽  
Author(s):  
Nils von Hentig ◽  
Jörn Lötsch
Keyword(s):  
Human Immunodeficiency Virus ◽  
Cytochrome P450 ◽  
Individual Therapy ◽  
Drug Formulation ◽  
Hiv Protease ◽  
Pharmacokinetic Analysis ◽  
Population Pharmacokinetic ◽  
Cytochrome P450 3A ◽  
Immunodeficiency Virus

ABSTRACT Inadequate concentrations of the human immunodeficiency virus (HIV) protease inhibitor saquinavir jeopardize individual therapy success or produce side effects despite treatment according to the current guidelines. We performed a population pharmacokinetic analysis with NONMEM and determined that the steady-state pharmacokinetics of saquinavir in 136 HIV type 1-infected adults was modulated by a decrease in saquinavir CL following coadministration of the cytochrome P450 3A inhibitors ritonavir and atazanavir. In contrast, age, sex, weight, pregnancy, and the pharmaceutical formulation exerted only minor, nonsignificant effects.

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