PHARMACOKINETICS STUDY OF C-14 MOXISYLYTE AFTER PERCUTANEOUS APPLICATION TO HAIRLESS RAT

The percutaneous pharmacokinetic parameters of C-14-thymoxamine (4-(2-dimethylaminoethoxy)-5-isopropyl-2-methyl phenyl acetate, moxisylyte, Carlytene(R)) were studied on female hairless rats. Animals received 30.3 mg/kg of thymoxamine-base (CAS 54-32-0) percutaneously (dorsal skin). The decrease of the radio-labelled compound on the skin surface (drug penetration) and the appearance of the total radioactivity in plasma (drug absorption) were measured. The time-course study of the total radioactivity measured on the skin surface indicates a biphasic profile with a rapid decrease during the first 4 h (t(1/2) fi om 0 to 4 h = 1.4 h) and then a less rapid one (t(1/2) after I? h approximate to 29 h). Plasma data demonstrated that C-14-thymoxamine was rapidly and almost entirely absorbed (91 %) after percutaneous application. The values of absorption parameters suggest that thymoxamine is a compound with a high absorption process using this route of administration. The t(max) value was about 2 h and the half-life of absorption was 0.70 it. Compared to the apparent half-life of elimination observed after oral or iv. administration (t(1/2) = 9 h), the elimination phase of thymoxamine,vas relatively rapid after percutaneous administration (t(1/2) = 15 h). The penetration/absorption phenomenon of thymoxamine base mainly located in the horny layer could explain the higher value of the half-life of elimination observed after per cutaneous administration.