Pharmacokinetics And Safety Of Transdermal And Oral Granisetron In Healthy Chinese Subjects: An Open-Label, Randomized, Crossover Study

Aims: To examine the pharmacokinetics and safety of granisetron during transdermal delivery and oral administration to healthy Chinese male subjects. Materials and methods: A single 34.3 mg/52 cm(2) transdermal delivery patch of granisetron and the 1-mg tablet of granisetron were dosed to subjects in an open-label, randomized, crossover study. Two dosing schemes were established: scheme 1, in which the 5-day oral administration phase of the tablet (the OA phase) (twice daily every 12 hours) was conducted, followed by the 6-day transdermal delivery phase of the patch (the TD phase); and scheme 2, in which these two phases were conducted in reverse order. Plasma concentrations of granisetron were measured according to high-performance liquid chromatography, and the following pharmacokinetic parameters were determined: C-avg [AUC(0-24,ss) (day 5)/24 for OA and AUC(24-44)/120 for TD], C-max, t(max), AUC, and T-1/2. Results: All of the subjects completed the TD phase, and 1 subject withdrew from the study due to increased alanine aminotransferase. The C-avg values for OA and TD were 2.95 +/- 1.60 ng/mL and 2.83 +/- 1.43 ng/mL. respectively. The C-max values at steady state for OA and TD were 5.98 +/- 2.27 ng/mL and 3.91 +/- 2.23 ng/mL. respectively. The incidences of adverse events (AEs) possibly or definitely related to OA and TD were 45.83% and 37.5%, respectively. No serious AEs were found in the two dosing schemes. Conclusion: The C-avg values determined through TD and OA were equivalent, indicating similar drug exposures. Therefore, the granisetron patch may be an alternative formulation for oral granisetron in Chinese individuals.