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Antimicrobial Agents and Chemotherapy, December 1999, p. 3025-3029, Vol. 43, No. 12
0066-4804/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Population Pharmacokinetics of Lamivudine in Adult Human Immunodeficiency Virus-Infected Patients Enrolled in Two Phase III Clinical Trials

Katy H. P. Moore,1,* Geoffrey J. Yuen,1 Elizabeth K. Hussey,1 Gary E. Pakes,1 Joseph J. Eron Jr.,2 and John A. Bartlett3

Glaxo Wellcome Inc., Research Triangle Park,1 Clinical HIV/AIDS Program, University of North Carolina at Chapel Hill, Chapel Hill,2 and Department of Medicine, Duke University Medical Center, Durham,3 North Carolina

Received 15 January 1999/Returned for modification 24 June 1999/Accepted 16 September 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.

* Corresponding author. Mailing address: Clinical Pharmacology, Glaxo Wellcome Inc., Five Moore Dr., Research Triangle Park, NC 27709. Phone: (919) 483-5542. Fax: (919) 483-6380. E-mail: km10993{at}glaxowellcome.com.

Antimicrobial Agents and Chemotherapy, December 1999, p. 3025-3029, Vol. 43, No. 12
0066-4804/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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