Pharmacokinetic evaluation of indomethacin ethyl ester-loaded nanoencapsules.
Goals were to evaluate indomethacin ethyl ester-nanoencapsules (IndOEt-NC) pharmacokinetics in rats and the in vivo ester conversion to indomethacin (IndOH). After i.v. and oral administration exclusively IndOH was detected in plasma. The AUC(IndOEt-NC)/AUC(IndOH) ratio after i.v. dosing was 0.68, accounting for dose and molecular weight differences, probably due to increased IndOH clearance after IndOEt-NC administration (alpha=0.05). The results confirm that antiedematogenic activity reported for IndOEt-NC is due to IndOH. Encapsulation did not protect the ester which in vivo is rapidly released and converted to IndOH, acting as a pro-drug.
Cattani
Vitória B
VB
Programa de Pós-Graduação em Ciências Farmacêuticas, Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
Pohlmann
Adriana R
AR
Dalla Costa
Teresa
T
D000284:Administration, Oral; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D001711:Biotransformation; D004339:Drug Compounding; D007213:Indomethacin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics; D007275:Injections, Intravenous; D008297:Male; D008954:Models, Biological; D053769:Nanocapsules; D011355:Prodrugs / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D051381:Rats; D017208:Rats, Wistar
D000894:Anti-Inflammatory Agents, Non-Steroidal; D053769:Nanocapsules; D011355:Prodrugs; C507313:indomethacin ethyl ester; D007213:Indomethacin