PHARMACOKINETICS OF CONTRAGESTAZOL(DL-111-IT),A NEW NON-STEROID ANTIFERTILITY AGENT IN MONKEYS

The pharmacokinetics of contragestazol,an early pregnancy temperating agent 3-(2-ethylphenyl)-5-(3-methoxyphenyl)-1H-1,2,4-triazole,DL-111-ITwas studied in Rhesus monkey.The blood concentration of DL-111-IT was determined by coupled column system HPLCmethed,Using an aqueous vehicle(20% cremophor EL in saline)DL-111-IT was injectedintravenously to monkeys at doses of 25,12.5 and 6.3 mg·kg-1.Blood drug concentration weremeasured.Using a programmable calculator the calculated pharmacokinetic parameters were asfollows:α1.83h^-1,4.71h^-1 and 3.61 h^-1;β0.15h-1,0.08h-1 and 0.09h-1;T1/2β6.63h,10.2 h and 10.1h;AUC 9.54 ug·h^-1·ml^-1,3.94 ug·h-1·ml^-1 and 3.75ug·h^-1·ml^-1.An oil solution of DL-111-IT was injected intramuscularly in monkeys at doses of 50,25 and12.5 mg·kg-1.Its blood concentrations were determined at 0.08,0.25,0.5,0.75,1,1.5,2,4,8,12 and 24 h after administration.From the time vs concentration curve,the pharmacokineticporameters obtained were as follows:Ka 0.98 h-1,1.03 h^-1 and 1.45 h^-1;Ke 0.42 h^-1,0.37h^-1 and 0.60 h^-1;T1/2 Ke 1.66 h,1.90 h and 1.16 h;T(peak)1.52 h,1.57 h and 1.09 h;AUC 4.86ug·h^-1·ml^-1,5.61 ug·h^-1·ml^-1 and 1.74 ug·h^-1·ml^-1.