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Population pharmacokinetics of lamivudine in adult human immunodeficiency virus-infected patients enrolled in two phase III clinical trials.

Publication ,  Journal Article
Moore, KH; Yuen, GJ; Hussey, EK; Pakes, GE; Eron, JJ; Bartlett, JA
Published in: Antimicrob Agents Chemother
December 1999

Lamivudine population pharmacokinetics were investigated by using nonlinear mixed-effect modelling (NONMEM) analysis of data from 394 human immunodeficiency virus (HIV)-infected patients treated with lamivudine (150 to 300 mg every 12 h) in two large, phase III clinical efficacy-safety trials, NUCA3001 and NUCA3002. Analyses of 1,477 serum lamivudine concentration determinations showed that population estimates for lamivudine oral clearance (CL/F; 25.1 liters/h) and volume of distribution (V/F; 128 liters) were similar to values previously reported for HIV-infected patients in phase I pharmacokinetic studies. Lamivudine CL/F was significantly influenced by the covariates creatinine clearance and weight and not affected by age, Centers for Disease Control and Prevention (CDC) classification, CD4(+) cell count, HIV type 1 (HIV-1) RNA PCR, or gender and race when CL/F was corrected for differences in patient weight. The population estimate for lamivudine V/F was not significantly influenced by the covariates gender, race, age, weight, renal function, HIV-1 RNA PCR, or CDC classification and CD4(+) cell count when creatinine clearance was included with CL/F in the model. Lamivudine disposition was significantly influenced by renal function. However, as only three patients had an estimated creatinine clearance of <60 ml/min, dosage adjustments for patients with impaired renal function should not be determined based on the population parameters derived in this analysis.

Duke Scholars

Published In

Antimicrob Agents Chemother

DOI

ISSN

0066-4804

Publication Date

December 1999

Volume

43

Issue

12

Start / End Page

3025 / 3029

Location

United States

Related Subject Headings

  • Regression Analysis
  • Population
  • Nonlinear Dynamics
  • Middle Aged
  • Microbiology
  • Male
  • Lamivudine
  • Humans
  • HIV Infections
  • Female
 

Citation

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Moore, K. H., Yuen, G. J., Hussey, E. K., Pakes, G. E., Eron, J. J., & Bartlett, J. A. (1999). Population pharmacokinetics of lamivudine in adult human immunodeficiency virus-infected patients enrolled in two phase III clinical trials. Antimicrob Agents Chemother, 43(12), 3025–3029. https://doi.org/10.1128/AAC.43.12.3025
Moore, K. H., G. J. Yuen, E. K. Hussey, G. E. Pakes, J. J. Eron, and J. A. Bartlett. “Population pharmacokinetics of lamivudine in adult human immunodeficiency virus-infected patients enrolled in two phase III clinical trials.Antimicrob Agents Chemother 43, no. 12 (December 1999): 3025–29. https://doi.org/10.1128/AAC.43.12.3025.
Moore KH, Yuen GJ, Hussey EK, Pakes GE, Eron JJ, Bartlett JA. Population pharmacokinetics of lamivudine in adult human immunodeficiency virus-infected patients enrolled in two phase III clinical trials. Antimicrob Agents Chemother. 1999 Dec;43(12):3025–9.
Moore, K. H., et al. “Population pharmacokinetics of lamivudine in adult human immunodeficiency virus-infected patients enrolled in two phase III clinical trials.Antimicrob Agents Chemother, vol. 43, no. 12, Dec. 1999, pp. 3025–29. Pubmed, doi:10.1128/AAC.43.12.3025.
Moore KH, Yuen GJ, Hussey EK, Pakes GE, Eron JJ, Bartlett JA. Population pharmacokinetics of lamivudine in adult human immunodeficiency virus-infected patients enrolled in two phase III clinical trials. Antimicrob Agents Chemother. 1999 Dec;43(12):3025–3029.

Published In

Antimicrob Agents Chemother

DOI

ISSN

0066-4804

Publication Date

December 1999

Volume

43

Issue

12

Start / End Page

3025 / 3029

Location

United States

Related Subject Headings

  • Regression Analysis
  • Population
  • Nonlinear Dynamics
  • Middle Aged
  • Microbiology
  • Male
  • Lamivudine
  • Humans
  • HIV Infections
  • Female