The disposition and metabolism of GW695634: a non-nucleoside reverse transcriptase inhibitor (NNRTi) for treatment of HIV/AIDS.
GW695634 is the prodrug of GW678248, a novel non-nucleoside reverse transcriptase inhibitor with potent antiviral activity against HIV/AIDS efavirenz- and nevirapine-resistant viruses. In mice, rats, and monkeys following oral administration of [(14)C]GW695634, the primary pathway of metabolic clearance was by amide hydrolysis and the main route of elimination (46%-75% of the dose) was in the feces. The primary metabolic pathway of clearance for GW695634 and GW678248 in the preclinical species was by amide hydrolysis. At least six metabolites were observed that were the products of GW695634 and GW678248 amide hydrolysis.
de Serres
Mark
M
Department of Drug Metabolism and Pharmacokinetics, Preclinical Drug Metabolism and Pharmacokinetics, GlaxoSmithKline, Inc., Research Triangle Park, 5 Moore Drive, NC 27709, USA. mark.m.deserres@gsk.com
Moss
Lee
L
Sigafoos
James
J
Sefler
Andrea
A
Castellino
Stephen
S
Bowers
Gary
G
Serabjit-Singh
Cosette
C
D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy; D000818:Animals; D001577:Benzophenones / Q000032:analysis / Q000378:metabolism* / Q000627:therapeutic use; D001646:Bile / Q000737:chemistry; D002250:Carbon Radioisotopes; D002851:Chromatography, High Pressure Liquid; D005243:Feces / Q000737:chemistry; D005260:Female; D008252:Macaca fascicularis; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D051381:Rats; D017207:Rats, Sprague-Dawley; D018894:Reverse Transcriptase Inhibitors / Q000032:analysis / Q000378:metabolism* / Q000627:therapeutic use; D013449:Sulfonamides / Q000032:analysis / Q000378:metabolism* / Q000627:therapeutic use
D001577:Benzophenones; D002250:Carbon Radioisotopes; C551634:N-(4-(((4-chloro-2-(3-chloro-5-cyanobenzoyl)phenoxy)acetyl)amino)-3-methylphenyl)sulfonylpropanamide; D018894:Reverse Transcriptase Inhibitors; D013449:Sulfonamides