Pharmacokinetics study of 14C-moxisylyte after percutaneous application to hairless rat.
The percutaneous pharmacokinetic parameters of 14C-thymoxamine (4-(2-dimethylaminoethoxy)-5-isopropyl-2-methyl phenyl acetate, moxisylyte, Carlytène) 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 radiolabelled 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 h (t1/2 from 0 to 4 h = 1.4 h) and then a less rapid one (t1/2 after 4 h approximately 29 h). Plasma data demonstrated that 14C-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 h. Compared to the apparent half-life of elimination observed after oral or i.v. administration (t1/2 = 9 h),the elimination phase of thymoxamine was relatively rapid after percutaneous administration (t1/2 = 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 percutaneous administration.
Neau
B
B
ADME Bioanalyses, Parc Haute Technology Sophia Antipolis, Mougins, France.
Roux
J
J
Courtiol
C
C
Lambrey
B
B
Marty
J P
JP
D000279:Administration, Cutaneous; D000284:Administration, Oral; D000317:Adrenergic alpha-Antagonists / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000818:Animals; D005260:Female; D006207:Half-Life; D007275:Injections, Intravenous; D013948:Moxisylyte / Q000008:administration & dosage / Q000493:pharmacokinetics*; D051381:Rats; D011923:Rats, Nude; D012869:Skin Absorption
D000317:Adrenergic alpha-Antagonists; D013948:Moxisylyte