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.
