2nd International Workshop on Clinical Pharmacology of HIV Therapy  Noordwijk, The Netherlands    April 2 - 4, 2001 Poster:  Effects of Gender, Race, Age and Weight on the Pharmacokinetics of Lopinavir after Single-Dose Kaletra ™ R. Bertz, W. Lam, A. Hsu, G.R. Granneman, E. Sun; Abbott Laboratories, Abbott Park, IL

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Background: Kaletra is a protease inhibitor recently approved in the US for HIV treatment in combination with other antiretrovirals.  Lopinavir (LPV) mean C_trough exceeds its average protein binding corrected EC50 for wt-HIV by 75-fold when dosed at 400/100 mg BID.  The effects of gender, race, weight and age on the pharmacokinetics (PK) of LPV were explored.

Methods: PK data from 7 single-dose co-formulated capsule bioavailability studies in healthy adults were analyzed using ANCOVA. Study, gender and race were factors, age and body weight were covariates in the statistical model. A dose of 400/100 or 400/200 mg LPV/ritonavir was taken with food; the study factor in the model accounted for differences in dose. PK parameters were log-transformed C_max, AUC and C₂₄/C_max (effective t_1/2). Interaction terms were not significant; none were included in final model. Race effects were compared pairwise.

Results: Data from 194 subjects were analyzed, 50 female and 144 male. Most were Caucasian (157), 17 Hispanic and 20 Black.  Subject age ranged from 18 to 55 yr (mean 31.6) with a weight range of 54.5 to 100.3 kg (mean 75.7). No statistically significant effect of gender (p >0.35) or age (p >0.30) was noted for any PK parameter. Weight was statistically significant for both AUC and C_max (p <0.001), but not effective t1/2 (p=0.14). Subjects with lower body weight tend-ed to have higher LPV C_max and AUC; an approximate 20% increase in AUC would be predicted for a 25% decrease in body weight. Race was marginally significant for C_max (p=0.052). Blacks had slightly lower LPV AUC (-14%, p=0.053) and C_max (-14%, p=0.02) than Caucasians. Differences are probably not clinically relevant as reflected by similar efficacy results for Blacks and Caucasians in a large Phase 3 trial, 863.

Conclusion: Of the demographic factors explored in a healthy adult population, body weight was the most significant predictor of LPV PK after single doses of Kaletra.

INTRODUCTION

• Kaletra (lopinavir/ritonavir or lopinavir/r) is an HIV-protease inhibitor recently approved in the United States for treatment of HIV in combination with other anti-retrovirals
  
  
• Clinical adult dose is 400/100 mg BID taken with food
  
  
• At the clinical dose, lopinavir mean Ctrough exceeds mean protein-binding corrected EC50 for wild-type HIV by >75-fold

OBJECTIVE

• To explore the effect of demographic variables, gender, race, weight and age, on the pharmacokinetics of lopinavir co-administered with ritonavir 

METHODS

• Data across seven bioavailability studies were examined

– Single-dose capsule co-formulations of lopinavir/r

• Lopinavir/r 400/100 mg (4 studies, N=144) 
• Lopinavir/r 400/200 mg (3 studies, N=50)

– Non-fasting conditions

TOP

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Poster:  Effects of Gender, Race, Age and Weight on the Pharmacokinetics of Lopinavir after Single-Dose Kaletra ™

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