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Lamivudine/Zidovudine as a Combined Formulation Tablet: Bioequivalence Compared with Lamivudine and Zidovudine Administered Concurrently and the Effect of Food on Absorption

1999; Wiley; Volume: 39; Issue: 6 Linguagem: Inglês

10.1177/00912709922008209

1552-4604

Katy H. P. Moore, Shuching Shaw, Aziz Laurent, Peggy Lloyd, Benjamin Duncan, David M. Morris, Michael O'Mara, Gary E. Pakes,

HIV Research and Treatment

A single‐center, open‐label, three‐way crossover study was conducted in 24 healthy subjects to assess (1) the bioequivalence of a combined lamivudine 150 mg/zidovudine 300 mg tablet relative to the separate brand‐name components administered concurrently and (2) the effect of food on the bioavailability of the drugs from the combination tablet. The subjects were randomly assigned to receive each of the following three treatments, separated by a 5‐ to 7‐day washout period: one lamivudine/zidovudine combination tablet after an overnight fast, one lamivudine 150 mg tablet and one zidovudine 300 mg tablet simultaneously after an overnight fast, or one lamivudine/zidovudine combination tablet 5 minutes after completing a standardized high‐fat breakfast (67 g fat, 58 g carbohydrate, and 33 g protein). Serial blood samples were collected up to 24 hours postdose for the determination of lamivudine and zidovudine plasma concentrations. Standard pharmacokinetic parameters were estimated. Treatments were considered bioequivalent if 90% confidence intervals for the ratio of least squares (LS) means for the lamivudine and zidovudine area under the plasma concentration‐time curve (AUC ∞ ) and maximum observed plasma concentration (C max ) fell entirely within 0.80 to 1.25 for log‐transformed parameters. The combined lamivudine/zidovudine tablet was bioequivalent in the extent (AUC ∞ ) and rate of absorption (C max and time of C max [t max ]) to the individual brand‐name drug components administered concurrently under fasted conditions. Geometric LS mean ratios and 90% confidence intervals for AUC ∞ and C max were 0.97 (0.92, 1.03) and 0.94 (0.84, 1.06), respectively, for lamivudine and 0.99 (0.91, 1.07) and 0.97 (0.82, 1.15), respectively, for zidovudine. The extent of absorption of lamivudine and zidovudine from the combination tablet was not altered by administration with meals, indicating that this formulation may be administered with or without food. However, food slowed the rate of absorption, delayed the t max , and reduced the C max of lamivudine and zidovudine. These changes were not considered clinically important. All formulations were well tolerated under fasted and fed conditions.