The pharmacokinetics of 1,3-di(4-imidazolino-2-methoxyphenoxy) propane.lactate (DMP.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 following iv and po administrations of DMP.lactate containing trace amounts of [14C]DMP.HCl. Following the iv administration of [14C]DMP.lactate (2.5 mg/kg), plasma concentrations of DMP declined in a biexponential manner and were measurable to 48 hr. The terminal elimination half-life was 37.7 hr. The mean AUC0-infinity of DMP was 1.58 micrograms.hr/ml. The volume of distribution was 89 liters/kg and the body clearance was 27 ml/min/kg. The disposition of total radioactivity was similar to that of DMP. Approximately 14% of the dose was eliminated in urine as DMP or total radioactivity. Renal clearance was 10% of the body clearance. Following the po administration of [14C]DMP.lactate (14 mg/kg) the mean Cmax of total radioactivity and DMP was 0.20 and 0.17 micrograms/ml, respectively. The respective mean AUC0-T was 0.37 and 0.21 micrograms.hr/ml. The mean oral bioavailability based on DMP plasma concentrations was 2.4%. The mean Cmax of DMP following a 100 mg/kg po dose of DMP.lactate was 14 micrograms/ml and the AUC0-T was 1.87 micrograms.ml/hr; the bioavailability was 3.2%. Approximately 1% of the orally administered dose was eliminated in urine as DMP.
Bekersky
I
I
Department of Pharmacology and Toxicology, Fujisawa Pharmaceutical Company, Deerfield, Illinois 60015.
Puhl
R J
RJ
Hanson
G
G
Mong
S
S
D000284:Administration, Oral; D000818:Animals; D000890:Anti-Infective Agents / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D001682:Biological Availability; D002851:Chromatography, High Pressure Liquid; D004285:Dogs; D006207:Half-Life; D007275:Injections, Intravenous; D008297:Male; D009894:Opportunistic Infections / Q000188:drug therapy*; D010419:Pentamidine / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics / Q000652:urine
D000890:Anti-Infective Agents; C065259:1,3-di-(4-imidazolino-2-methoxyphenoxy)propane; D010419:Pentamidine