Pharmacokinetics and safety of transdermal and oral granisetron in healthy Chinese subjects: An open-label, randomized, crossover study

Abstract

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 cm² 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_24-144/120 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. .