Ge. Chittick et al., Abacavir: Absolute bioavailability, bioequivalence of three oral formulations, and effect of food, PHARMACOTHE, 19(8), 1999, pp. 932-942
Study Objectives. Study A: to determine the absolute bioavailability of a s
ingle 300-mg abacavir hemisulfate tablet. Study B: to determine the bioequi
valence of two oral abacavir formulations (300-mg hemisulfate tablet, 100-m
g succinate caplet), the effect of food on the bioavailability of the 300-m
g hemisulfate tablet, and the bioavailability of the hemisulfate tablet rel
ative to the hemisulfate solution.
Design. Phase I, randomized, open-label, balanced two- (study A) and three-
or four-period (study B), crossover studies.
Setting. Two clinical research centers.
Subjects. Six men infected with the human immunodeficiency virus (HIV), age
d 27-39 years (study A), and 18 HIV-infected men and women, aged 21-50 year
s (study B).
Interventions. In study A, all subjects received a single, oral 300-mg tabl
et of abacavir hemisulfate or a single, intravenous infusion of abacavir he
misulfate 150 mg over 60 minutes. In study B, all subjects received each of
three single-dose treatments: three 100-mg abacavir succinate caplets in a
fasted state, one 300-mg abacavir hemisulfate tablet in a fasted state, an
d one 300-mg abacavir hemisulfate tablet with a high-fat breakfast. Twelve
subjects in study B also received a fourth treatment of abacavir hemisulfat
e 300 mg as an oral solution in a fasted state. Plasma samples collected fo
r 24 hours (study A) or 12 hours (study B), and urine samples collected for
12 hours (study A) were analyzed by validated high-performance liquid chro
matographic methods.
Measurements and Main Results. Abacavir pharmacokinetic parameters were cal
culated using standard, noncompartmental methods. In study A, the geometric
least square (GLS) mean absolute bioavailability of oral abacavir was 83%
(range 65-107%). In study B, the hemisulfate tablet was bioequivalent to th
e succinate caplet, but its time to maximum concentration (T-max) occurred
30 minutes earlier. Administration of the abacavir hemisulfate tablet with
food had no effect on area under the curve from time zero to infinity (AUC(
0-infinity)), decreased maximum concentration (C-max) by 26%, and delayed T
-max by 38 minutes. The relative bioavailability (GLS mean AUC(0-infinity)
ratio) of the 300-mg abacavir hemisulfate tablet to solution was 101%, C-ma
x was 11% lower, and T-max was unchanged. The most common drug-related adve
rse events associated with abacavir were nausea, vomiting, abdominal pain,
and headache, all of which were mild.
Conclusion. Based on our results, abacavir is safe and well tolerated and c
an be administered with or without meals.