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Bioavailability of two oral suspension and two oral tablet formulations of acyclovir 400 mg: two single-dose, open-label, randomized, two-period crossover comparisons in healthy Mexican adult subjects.

Author(s): Palma-Aguirre JA, Absalon-Reyes JA, Novoa-Heckel G, de Lago A, Oliva I, Rodriguez Z, Gonzalez-de la Parra M, Burke-Fraga V, Namur S

Affiliation(s): Centro de Estudios Cientificos y Clinicos Pharma, S.A. de C.V., Mexico City, Mexico.

Publication date & source: 2007-06, Clin Ther., 29(6):1146-52.

Publication type: Randomized Controlled Trial; Research Support, Non-U.S. Gov't

BACKGROUND: Acyclovir is an important antiviral drug, used extensively for treatment of herpes simplex and varicella zoster. Six oral generic formulations of acyclovir are available in Mexico; however, a literature search failed to identify data information concerning the bioavailability of these formulations in the Mexican population. OBJECTIVE: The aim of these 2 studies was to compare the bioavailability of 4 oral formulations of acyclovir 400 mg--2 tablet formulations and 2 suspension formulations--with their corresponding listed drug references in Mexico (a list issued by Mexican Health Authorities). METHODS: Two separate, single-dose, open-label, randomized, 2-period crossover studies were conducted at the Centro de Estudios Cientificos y Clinicos Pharma, S.A. de C.V. (clinical unit), Mexico City, Mexico. For each study, a different set of eligible subjects were selected. They included healthy Mexican volunteers of either sex. For each study, subjects were randomly assigned to receive 1 test formulation of acyclovir 400 mg followed by the reference formulation, or vice versa, with a 1-week washout period between doses. After a 12-hour (overnight) fast, subjects received a single 400-mg dose (tablet or 10-mL suspension) of the corresponding formulation. For the analysis of pharmacokinetic properties, including C(max), AUC from time 0 (baseline) to time t (AUC(0-t)), and AUC from baseline to infinity (AUC(0-infinity)), blood samples were drawn at baseline, 0.25, 0.5, 0.75, 1.0, 1.25, 1.5, 1.75, 2, 3, 4, 6, 8, 12, and 24 hours after dosing. The formulations were considered bioequivalent if the natural logarithm (ln)-transformed ratios of Cmax and AUC were within the predetermined equivalence range of 80% to 125% and if P <or= 0.05 for the 90% CIs. Tolerability was assessed by monitoring vital signs, laboratory analysis results, and subject interviews. RESULTS: Twenty-six subjects were enrolled in the study for the suspension dosage form and 25 completed it (13 men, 12 women; mean age, 22.2 years). Subjects in the suspension-dosage form study had the following characteristics: age range, 18 to 48 years; weight range, 46 to 86 kg; and height range, 145 to 179 cm. Thirteen subjects received the suspension-test formulation first. Twenty-four subjects were enrolled in the study for the tablet dosage form; all of them concluded the study (13 men, 11 women; mean age, 24.7 years). Subjects had the following characteristics for the tablet-dosage form study: age range, 18 to 49 years; weight range, 46 to 84 kg; and height range, 147 to 185 cm. Twelve subjects received the tablet-test formulation first. No period or sequence effect was observed in either study. For the suspension dosage form, the 90% CIs for the corresponding ratios of ln Cmax, ln AuC(0-t), and ln AUC(0-infinity) were 106.55 to 116.11, 99.29 to 113.19, and 98.37 to 112.04, respectively (all, P < 0.05). For the tablet dosage form, the 90% CIs for the corresponding ratios of ln Cmax, ln AUC(0-t), and ln AUC(0-infinity) were 83.46 to 103.64, 86.16 to 111.05, and 87.77 to 109.99, respectively (all, P < 0.05). CONCLUSIONS: In these 2 studies in healthy subjects, single, 400-mg doses of the test brand of acyclovir administered either in tablet or suspension form, appeared to be bioequivalent to the reference brand based on the rate and extent of absorption in accordance with the definition of the US Food and Drug Administration. All formulations were well tolerated.

Page last updated: 2007-10-18

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