Pharmacokinetics of a granisetron transdermal system for the treatment of chemotherapy-induced nausea and vomiting.
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; t(1/2) was 36 h. With oral dosing, overall exposure after 5 days was 306 ng/mL.h, and C(avg) 2.6 ng/mL. This corresponded to an AUC(0-infinity) for the 52 cm(2) patch of 420 ng/mL.h and C(avg) 2.2 ng/mL over 6 days. Clearance was not affected by age, gender, weight, or renal function.


CONCLUSIONS
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.
Howell
Julian
J
Clinical Development, ProStrakan Ltd, Galashiels, UK. julian.howell@prostrakan.com
Smeets
Jean
J
Drenth
Henk-Jan
HJ
Gill
David
D
D000279:Administration, Cutaneous; D000293:Adolescent; D000328:Adult; D000375:Aging / Q000378:metabolism; D000932:Antiemetics / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000009:adverse effects*; D019540:Area Under Curve; D001682:Biological Availability; D002626:Chemistry, Pharmaceutical; D003404:Creatinine / Q000378:metabolism; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D017829:Granisetron / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D006207:Half-Life; D006801:Humans; D008297:Male; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced / Q000517:prevention & control*; D012727:Sex Characteristics; D014839:Vomiting / Q000139:chemically induced / Q000517:prevention & control*; D055815:Young Adult
D000932:Antiemetics; D000970:Antineoplastic Agents; D003404:Creatinine; D017829:Granisetron