Pharmacokinetics of moxisylyte in healthy volunteers after intravenous infusion and intracavernous administration with and without a penile tourniquet.
The concentration-time profiles of metabolites of moxisylyte (or thymoxamine), an alpha-blocking agent, were investigated in 18 healthy volunteers after intravenous (i.v.) and intracavernous (i.c.) administrations with and without a tourniquet. Four metabolites, unconjugated desacetylmoxisylyte (DAM), DAM glucuronide, and DAM and monodesmethylated DAM (MDAM) sulfates, were found in plasma and urine. For all metabolites, tmax was significantly increased after i.c. administrations and Cmax was significantly decreased. Maximum plasma level of unconjugated DAM was lower after i.c. administration with (1.81-fold) and without (1.26-fold) a tourniquet than after i.v. administration (43.6 +/- 19.6 ng/ml). The elimination half-life of each metabolite showed no change between the three treatments. The difference of 19 min between the mean residence times of unconjugated DAM after i.c. administration with and without a tourniquet may be compared with the difference between the mean duration of the intumescence, that is, 19 min (73 and 54 min with and without a tourniquet, respectively). Total percentages of metabolites recovered in urine were 66.2 +/- 20.9, 61.4 +/- 12.2, and 58.7 +/- 9.1% after i.v. and i.c. administrations with and without a tourniquet, respectively. In conclusion, tourniquet placed before i.c. administration increased the mean residence time of unconjugated DAM of approximately 25% and seemed to increase the efficacy of the drug in healthy volunteers.
Costa
P
P
Service d'Urologie-Andrologie, CHU G. Doumergue, Nîmes, France.
Bressolle
F
F
Mottet
N
N
Rouzier-Panis
R
R
Navratil
H
H
Marquer
C
C
D000328:Adult; D000704:Analysis of Variance; D018592:Cross-Over Studies; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D013948:Moxisylyte / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D010410:Penile Erection / Q000187:drug effects*; D014111:Tourniquets; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine
D014665:Vasodilator Agents; D013948:Moxisylyte