PT  - JOURNAL ARTICLE
AU  - M F Grubb
AU  - Y N Wong
AU  - D L Burcham
AU  - P L Saxton
AU  - C Y Quon
AU  - S M Huang
TI  - Pharmacokinetics of HIV protease inhibitor DMP 323 in rats and dogs.
DP  - 1994 Sep 01
TA  - Drug Metabolism and Disposition
PG  - 709--712
VI  - 22
IP  - 5
4099  - http://dmd.aspetjournals.org/content/22/5/709.short
4100  - http://dmd.aspetjournals.org/content/22/5/709.full
SO  - Drug Metab Dispos1994 Sep 01; 22
AB  - DMP 323 is a symmetrically substituted cyclic urea compound with demonstrated activity against human immunodeficiency virus (HIV) in vitro. DMP 323 has been measured in rat and dog plasma via liquid-liquid extraction and HPLC. The limit of quantitation is 10 ng/ml using 0.5 ml plasma. Following an intravenous dose of 5 mg/kg to rats, DMP 323 exhibited an apparent volume of distribution at steady-state of 6.36 liters/kg and clearance of 7.12 liters/hr/kg. The same dose administered intravenously to dogs resulted in apparent volume of distribution at steady-state and clearance values of 2.28 liters/kg and 1.48 liters/hr/kg, respectively. Elimination half-lives were 0.95 hr in rats and 1.80 hr in dogs. DMP 323 was rapidly absorbed from oral solution doses in rats (3, 5, and 10 mg/kg) and dogs (5 and 10 mg/kg), achieving maximum plasma concentrations in 1 hr or less in both species. Absolute bioavailability of DMP 323 from oral doses ranged from 15 to 27% in rats and from 37 to 38% in dogs. Pharmacokinetics were unchanged in rats and dogs over 8-day t.i.d. and 5-day b.i.d. multiple oral dose regimens, respectively. Oral doses administered to fed animals resulted in lower plasma concentrations of DMP 323 than the same doses administered to fasted animals. Because of its in vitro high potency and acceptable pharmacokinetics, DMP 323 seems to be a worthy candidate for further study in the effort to develop an inhibitor of HIV protease for use in the therapy of AIDS.