Wynne B, Lewis R, Bianchine JR, Narang P; International Conference on AIDS.
Int Conf AIDS. 1992 Jul 19-24; 8: B134 (abstract no. PoB 3282).
Adria Laboratories, Dublin, OH 43017.
OBJECTIVE: RIF, an antimycobacterial, has been shown to be a good prophylactic for Mycobacterium avium Complex (MAC) opportunistic infections in HIV (+) patients. To provide dosing guidance to patients, this study was designed to assess the G.I. absorption of the capsule dosage form relative to a solution, and to assess the effect of high-fat food. METHODS: Twelve (12) nonsmoking, HNV participated in this randomized, three-way crossover trial. Each volunteer received a single 150 mg dose of RIF as a solution (Trmt. A, fasted), a capsule with (Trmt. B, post-prandial) and without high-fat food (Trmt. C, fasted) with a two-week washout period between treatments. Serial plasma and urine samples were obtained for 168 hours and 48 hours, respectively. RIF and its active metabolite, 25-O-deacetyl RIF (LM565), were assayed by a sensitive, validated HPLC procedure (less than 15% imprecision and bias from QCs). AUC0-t, Cmax, and AUC0-infinity from treatments C vs. A and B vs. C were analyzed with/without log-transformation. Homogeneity of variance in estimates was first assessed by the Bartlett's test. ANOVA model tested for the effect of treatment sequence, volunteer within sequence, study phase and treatment. All tests of significance were performed at p = 0.05 level. RESULTS: The mean (sd) Cmax of RIF in plasma was 238 (65), 156 (52) and 188 (50) ng/mL, Tmax 2.5 (0.4), 5.4 (1.6), and 3.0 (1.1) hours, and the AUC0-infinity 2989 (726), 2640 (891) and 2516 (601) ng.Hr/mL following solution (A), capsule (B, fed) and capsule (C, fasted) dosing, respectively. Unchanged RIF in urine was 11.0 (2.4)%, 11.4 (4.9)% and 9.1 (2.1)%, respectively, after Trmt. A, B, and C. Corresponding AUC0-infinity(m) for LM565 were 400 (184), 385 (187) and 298 (102) ng.Hr/mL. ANOVA showed a significant decrease (p = 0.027) in RIF Cmax after Trmt. C relative to A (fasted). An increase (p = 0.0001) in Tmax was seen after Trmt. B (post-prandial) compared to Trmt. C (fasted) for the capsule dosage form. Least-squares AUC estimates with or without food were not different (power to detect a 20% difference greater than 85%). DISCUSSION & CONCLUSION: Although the rate appears to be slower in the presence of high-fat food, the extent of absorption from the capsule dosage form is not altered. Relative bioavailability (Frel) of capsule (fasted) was 85 (18.5)%, whereas the mean Frel (fed/fasted) was 106.0 (24.1)%. Similar conclusions about absorption were also reached from the LM565 data. Therefore, in HIV (+) patients receiving RIF for MAC prophylaxis, it can be expected that the exposure of tissues to this new antimycobacterial and to its active metabolite will not be altered if RIF was administered with or without food.
Publication Types:
Keywords:
- 25-desacetylrifabutin
- Absorption
- Accidents
- Acquired Immunodeficiency Syndrome
- Area Under Curve
- Biological Availability
- Capsules
- Cross-Over Studies
- Fasting
- Food
- HIV Infections
- HIV Seropositivity
- Humans
- Intestinal Absorption
- Mycobacterium avium-intracellulare Infection
- Rifabutin
- injuries
- pharmacokinetics
Other ID:
UI: 102198726
From Meeting Abstracts