Pharmacokinetics of a granisetron transdermal system for the treatment of chemotherapy-induced nausea and vomiting

Abstract

Objective. To determine the pharmacokinetic (PK) profile of granisetron transdermal formulation and examine its possible relationship with age, gender, and renal function. Methods. This article describes a Phase I PK study and a post hoc pooled population PK analysis. The Phase I study was a randomized, cross-over study that assessed PK parameters of three granisetron patch sizes and oral granisetron. The pooled population PK analysis included data from three trials in healthy subjects (n = 48) and from Phase II and III studies in patients with cancer (n = 793). The population PK model was used to investigate granisetron exposure and its possible relationship with age, gender, and renal function. Results. Following oral dosing, plasma granisetron concentration was quantifiable at 1 h, and maximal mean concentration (4.7 ng/mL) was reached 2 h after administration. With transdermal application, maximal concentration was reached 48 h post-application; t1/2 was 36 h. With oral dosing, overall exposure after 5 days was 306 ng/mL·h, and Cavg 2.6 ng/mL. This corresponded to an AUC0—∞ for the 52 cm2 patch of 420 ng/mL·h and Cavg 2.2 ng/mL over 6 days. Clearance was not affected by age, gender, weight, or renal function. Conclusion. The 52 cm 2 granisetron patch achieves a similar exposure to that of a 2 mg oral dose and provides continuous delivery of granisetron over 6 days. The patch may have utility in treating chemotherapy-induced nausea and vomiting where prolonged drug delivery is advantageous. No dose adjustments would be needed based on age or renal function.