STUDY OBJECTIVES: Study A: to determine the absolute bioavailability of a single 300-mg abacavir hemisulfate tablet. Study B: to determine the bioequivalence of two oral abacavir formulations (300-mg hemisulfate tablet, 100-mg succinate caplet), the effect of food on the bioavailability of the 300-mg hemisulfate tablet, and the bioavailability of the hemisulfate tablet relative 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), aged 27-39 years (study A), and 18 HIV-infected men and women, aged 21-50 years (study B). INTERVENTIONS: In study A, all subjects received a single, oral 300-mg tablet of abacavir hemisulfate or a single, intravenous infusion of abacavir hemisulfate 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, and one 300-mg abacavir hemisulfate tablet with a high-fat breakfast. Twelve subjects in study B also received a fourth treatment of abacavir hemisulfate 300 mg as an oral solution in a fasted state. Plasma samples collected for 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 chromatographic methods. MEASUREMENTS AND MAIN RESULTS:Abacavir pharmacokinetic parameters were calculated 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 the succinate caplet, but its time to maximum concentration (Tmax) 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 (AUC0-infinity), decreased maximum concentration (Cmax) by 26%, and delayed Tmax by 38 minutes. The relative bioavailability (GLS mean AUC0-infinity ratio) of the 300-mg abacavir hemisulfate tablet to solution was 101%, Cmax was 11% lower, and Tmax was unchanged. The most common drug-related adverse 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 can be administered with or without meals.
RCT Entities:
STUDY OBJECTIVES: Study A: to determine the absolute bioavailability of a single 300-mg abacavir hemisulfate tablet. Study B: to determine the bioequivalence of two oral abacavir formulations (300-mg hemisulfate tablet, 100-mg succinate caplet), the effect of food on the bioavailability of the 300-mg hemisulfate tablet, and the bioavailability of the hemisulfate tablet relative 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), aged 27-39 years (study A), and 18 HIV-infectedmen and women, aged 21-50 years (study B). INTERVENTIONS: In study A, all subjects received a single, oral 300-mg tablet of abacavir hemisulfate or a single, intravenous infusion of abacavir hemisulfate 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, and one 300-mg abacavir hemisulfate tablet with a high-fat breakfast. Twelve subjects in study B also received a fourth treatment of abacavir hemisulfate 300 mg as an oral solution in a fasted state. Plasma samples collected for 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 chromatographic methods. MEASUREMENTS AND MAIN RESULTS:Abacavir pharmacokinetic parameters were calculated 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 the succinate caplet, but its time to maximum concentration (Tmax) 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 (AUC0-infinity), decreased maximum concentration (Cmax) by 26%, and delayed Tmax by 38 minutes. The relative bioavailability (GLS mean AUC0-infinity ratio) of the 300-mg abacavir hemisulfate tablet to solution was 101%, Cmax was 11% lower, and Tmax was unchanged. The most common drug-related adverse 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 can be administered with or without meals.
Authors: Chong-Hui Gu; Hua Li; Jaquan Levons; Kimberley Lentz; Rajesh B Gandhi; Krishnaswamy Raghavan; Ronald L Smith Journal: Pharm Res Date: 2007-03-24 Impact factor: 4.200
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Authors: Shane J Cross; John H Rodman; Jane C Lindsey; Brian L Robbins; Charles H Rose; Geoffrey J Yuen; Lawrence J D'angelo Journal: J Acquir Immune Defic Syndr Date: 2009-05-01 Impact factor: 3.731
Authors: J W Sleasman; B L Robbins; S J Cross; J C Lindsey; J M Kraimer; B E Heckman; H L Sprenger; N B Tustin; C H Rose; P A Poston; E F Neal; G E Pakes; M Nikanjam; E V Capparelli Journal: Clin Pharmacol Ther Date: 2008-12-31 Impact factor: 6.875