Results from four pharmacokinetic studies of the granisetron transdermal system

Sally T Haislip,¹ James W Gilmore,¹ Julian D Howell<sup>2

1</sup>Georgia Cancer Specialists, Atlanta, GA, USA; ²Clinical Development, ProStrakan, Galashiels, UK

Introduction: Sancuso^® (granisetron transdermal system [GTDS]) is the first antiemetic agent for chemotherapy-induced nausea and vomiting and is available as a 52 cm² patch containing 34.3 mg of granisetron delivered transdermally at 3.1 mg/24 hours for up to 7 days. Four Phase I studies were performed to assess the pharmacokinetic profile of the GTDS.
Methods: The four Phase I studies in healthy adult volunteers were conducted to investigate the pharmacokinetics of GTDS with respect to patch placement on the body (study 1); age, body mass index, and tricep skinfold thickness (as a surrogate for cachectic or obese patients) (study 2); external heat (study 3); and consecutive GTDS patch administration or coadministration of GTDS with intravenous granisetron (study 4).
Results: In study 1 (n = 12), the systemic bioavailability of granisetron from a GTDS patch applied to the abdomen was similar to that seen after application to the upper arm. Findings from study 2 (n = 60) showed no effect of age, body mass index, or skinfold thickness on the pharmacokinetics of transdermally administered granisetron. The application of external heat to the GTDS patch in study 3 (n = 16) elicited a small increase in granisetron flux but had no significant effect on GTDS pharmacokinetics or adverse events. In study 4 (n = 12), consecutive GTDS patch administration, or coadministration of the GTDS patch with intravenous granisetron, demonstrated both immediate and extended granisetron delivery with evidence of minimal accumulation.
Conclusion: Findings from these four studies suggest that no GTDS dose adjustments are needed for patient age, body mass index, or tricep skinfold thickness. Also, should external heat (eg, sunlight or warm showers) be applied to the GTDS short-tem, there are unlikely to be significant adverse consequences. Both sequential GTDS patch administration and coadministration with intravenous granisetron may be feasible if clinically warranted.

Keywords: transdermal, chemotherapy-induced nausea and vomiting, antiemetic, granisetron, pharmacokinetics