Abacavir pharmacokinetics during chronic therapy in HIV-1-infected adolescents and young adults

Abstract

The pharmacokinetics of abacavir and its metabolites were investigated in 30 human immunodeficiency virus (HIV)-infected adolescents and young adults 13-25 years of age, equally divided into two groups: <18 years of age and >or=18 years of age. All the subjects received the recommended adult dose of 300 mg twice daily. The area under the plasma concentration-time curve (AUC) and half-life of abacavir did not differ significantly between the age groups or by gender or race, and there were only modest associations of age with apparent abacavir clearance and with volume of distribution. There were no significant correlations of carboxylate or glucuronide metabolite levels with age or gender, although glucuronide AUC was higher in Hispanic subjects than in African-American subjects. Zidovudine and lamivudine concentration profiles were also similar in the two age groups. A novel aspect of the study included an assessment of intracellular carbovir, zidovudine, and lamivudine triphosphate levels, and these were found to be similar in the two age-based groups. Overall, these findings suggest that current recommendations relating to adult dosages are appropriate for adolescents and young adults.

Figure 1

Plasma concentrations of abacavir (ABC) and its metabolites, abacavir-glucuronide (ABC-G) and abacavir-carboxylate (ABC-C) by age cohort; age <18 years (group 1) and ≥18 years (group 2). Thin solid lines represent individual concentration profiles in the younger subjects and thin broken lines represent data pertaining to the older subjects. The thicker solid and broken lines represent the median concentrations for groups 1 and 2, respectively.

Figure 2

Plasma concentrations of zidovudine (ZDV) and lamivudine (3TC) by age cohort, age <18 years (group 1) and ≥18 years (group 2). Thin solid lines represent individual concentration profiles in the younger subjects, and thin broken lines represent data relating to the older subjects. The thicker solid and broken lines represent the median concentrations for groups 1 and 2, respectively.

Figure 3

Intracellular carbovir-triphosphate (CBV-TP) concentrations are shown during the intervals between doses. The age cohort <18 years of age is represented by circles, and the cohort ≥18 years is represented by triangles. The broken line represents the population-based concentration profile.