[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-IT] was studied in Rhesus monkey. The blood concentration of DL-111-IT was determined by coupled column system HPLC method. Using an aqueous vehicle (20% cremophor EL in saline) DL-111-IT was injected intravenously to monkeys at doses of 25, 12.5 and 6.3 mg.kg-1. Blood drug concentration were measured. Using a programmable calculator the calculated pharmacokinetic parameters were as follows: alpha 1.83 h-1, 4.71 h-1 and 3.61 h-1, beta 0.15 h-1, 0.08 h-1 and 0.09 h-1; T1/2 beta 6.63 h, 10.2 h and 10.1 h; AUC 9.54 micrograms.h-1.ml-1, 3.94 micrograms.h-1.ml-1 and 3.75 micrograms.h-1.ml-1. An oil solution of DL-111-IT was injected intramuscularly in monkeys at doses of 50, 25 and 12.5 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 pharmacokinetic parameters obtained were as follows: Ka 0.98 h-1, 1.03 h-1 and 1.45 h-1; Ke 0.42 h-1, 0.37 h-1 and 0.60 h-1; T1/2Ke 1.66 h, 1.90 h and 1.16 h; T (peak) 1.52 h, 1.57 h and 1.09 h; AUC 4.86 micrograms.h-1.ml-1, 5.61 micrograms.h-1.ml-1 and 1.74 micrograms.h-1.ml-1.