In vivo percutaneous absorption of capsaicin, nonivamide and sodium nonivamide acetate from ointment bases: Pharmacokinetic analysis in rabbits

Nonivamide (NVA) and nonpungent sodium nonivamide acetate (SNA) are both synthetic derivatives of capsaicin. In this study, in vivo systemic drug plasma data of capsaicin, NVA and SNA following intravenous and transdermal ointment base administration in rabbits were performed to establish the pharmacokinetic analysis of these analogues. In order to describe the capsaicin, NVA and SNA plasma profiles observed, one-compartment pharmacokinetic open model for capsaicin and NVA, and two-compartment model for SNA was used in the i.v. plasma data. After the percutaneous administration, the plasma profiles between capsaicin and NVA were quite different although these two analogues showed similar physicochemical properties and intravenous pharmacokinetic parameters. The high plasma concentrations of SNA were obtained in the early period after transdermal application. This phenomenon suggested that SNA passes through skin via the intercellular and transappendageal routes. In the study of the in vivo percutaneous effect of NVA-SNA combined ointments, the result indicated that NVA and SNA could often act as the potent penetration enhancer for each other to higher absorption amount and bioavailability than individual NVA or SNA ointment base. The information of the pharmacokinetic analysis of capsaicin and its analogues in rabbits' are helpful for the development of capsaicin, NVA and SNA transdermal drug delivery system.