THE PHARMACOKINETICS OF ZOLINO-2-METHOXYPHENOXY)PROPANE-CENTER-DOT-LACTATE (DMP-CENTER-DOT-LACTATE), A NEW AGENT AGAINST OPPORTUNISTIC INFECTIONS, IN MALE BEAGLE DOGS

The pharmacokinetics and oral bioavailability of 1,3-di(4-imidazolino- 2-methoxyphenoxy) propane lactate (DMP) was determined in male dogs fo llowing iv and po administrations of DMP lactate containing trace amou nts of [C-14]DMP HCl. Following the iv administration of [C-14]DMP.lac tate (2.5 mg/kg), plasma concentrations of DMP declined in a biexponen tial manner and were measurable to 48 hr. The terminal elimination hal f life was 37.7 hr. The mean AUC(0-infinity) of DMP was 1.58 mu g hr/m l. The volume of distribution was 89 liters/kg and the body clearance was 27 ml/min/kg. The disposition of total radioactivity was similar t o that of DMP. Approximately 14% of the dose was eliminated in urine a s DMP or total radioactivity. Renal clearance was 10% of the body clea rance. Following the po administration of [C-14]DMP lactate (14 mg/kg) the mean C-max of total radioactivity and DMP was 0.20 and 0.17 mu g/ ml, respectively. The respective mean AUC(0-T) was 0.37 and 0.21 mu g hr/ml. The mean oral bioavailability based on DMP plasma concentration s was 2.4%. The mean C-max of DMP following a 100 mg/kg po dose of DMP lactate was 14 mu g/ml and the AUC(0-T) was 1.87 mu g.ml/ hr; the bio availability was 3.2%. Approximately 1% of the orally administered dos e was eliminated in urine as DMP.