title: P-glycoprotein effects of cyclic urea HIV protease inhibitor DMP 323 in competitional absorption studies.
abstract: Cyclic ureas form a perspective class of non-peptidic HIV-1 protease inhibitors with major bioavailability problems. Low absorption rates of DMP 323 as one of the first representatives led to investigations whether transport efflux pump P-glycoprotein (P-gp) within the intestine may be partly responsible for the low absorption rates. DMP 323 proved to be a P-gp substrate in competition studies with P-gp inhibitor ritonavir and H17 as a representative of another class of non-peptidic HIV-1 protease inhibitors. Intestinal DMP 323 absorption was mainly increased under co-application of both ritonavir and H17. DMP 323 used as a membrane efflux pump inhibitor itself showed little affinities to P-gp compared to H17 as strong P-gp inhibitor. So P-gp proved to play a decisive role in the low intestinal absorption of the cyclic urea representative DMP 323.
authors.affiliation: Department of Pharmacy, Institute of Pharmaceutical Chemistry, Martin Luther University, Halle, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Richter
authors.forename: Nóra
authors.initials: N
authors.lastname: Gyémánt
authors.forename: Joséf
authors.initials: J
authors.lastname: Molnár
authors.forename: Andreas
authors.initials: A
authors.lastname: Hilgeroth
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000037:antagonists & inhibitors / Q000502:physiology*; D000818:Animals; D001381:Azepines; D045744:Cell Line, Tumor; D017320:HIV Protease Inhibitors / Q000493:pharmacokinetics*; D007408:Intestinal Absorption / Q000187:drug effects; D008297:Male; D051379:Mice; D010539:Permeability; D051381:Rats; D017208:Rats, Wistar; D019438:Ritonavir / Q000494:pharmacology; D014508:Urea / Q000031:analogs & derivatives* / Q000493:pharmacokinetics
chemical_list: D018435:ATP Binding Cassette Transporter, Subfamily B; D001381:Azepines; D017320:HIV Protease Inhibitors; D014508:Urea; C085816:DMP 323; D019438:Ritonavir