Influence of rheumatoid arthritis in the enantioselective disposition of fenoprofen.
To investigate the influence of rheumatoid arthritis on the stereoselective disposition of fenoprofen administered as a racemic mixture, eight patients with rheumatoid arthritis receiving calcium rac-fenoprofen (200 mg/8 h) and 7 healthy volunteers given single oral dose (600 mg) were investigated. Serial blood samples and urine were collected from zero to 24 h after fenoprofen (FEN) administration. The following differences were observed between the (+)-(S) and (-)-(R)-FEN in the patients with rheumatoid arthritis (means 95% CI, Wilcoxon test, P < 0.05): C(max) 14.1 (12.5-15.8) versus 3.6 (2.5-4.7) microg/ml; AUC(ss) (0-8) 80.5 (67.3-93.7) versus 12.1 (8.8-15.4) microg.h/ml; Cl(T)/f 1.3 (1.0-1.5) versus 9.1 (6.5-11.8) l/h; and t(1/2) 3.1 (2.3-3.9) versus 1.2 (0.8-1.6) h. The Cl(T)/f of (-)-(R)-FEN was reduced in patients with rheumatoid arthritis when compared to healthy volunteers: 9.1 (6.5-11.8) versus 17.4 (13.9-20.9) l/h; P < 0.05 Mann-Whitney test. The administration of rac-FEN as a single dose to healthy volunteers or multiple doses to patients with rheumatoid arthritis resulted in lower Cl(T)/f for the (+)-(S)-FEN. The lower Cl(T)/f of (-)-(R)-FEN observed for patients with rheumatoid arthritis is consistent with lower clearance by inversion, although other metabolic pathways, drug interactions, and bioavailability of the individual enantiomers may also contribute to the difference.
Barissa
Giuliano Rodrigo
GR
Faculdade de Ciências Farmacêuticas de Ribeirão Preto-Universidade de São Paulo, Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, Avenida do Café s/n, Campus da USP, 14040-903 Ribeirão Preto, São Paulo, Brazil.
Poggi
Josiane Cristófani
JC
Donadi
Eduardo Antônio
EA
Dos Reis
Marina Lemos
ML
Lanchote
Vera Lucia
VL
D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry* / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001172:Arthritis, Rheumatoid / Q000378:metabolism*; D005260:Female; D005279:Fenoprofen / Q000737:chemistry* / Q000493:pharmacokinetics*; D020719:Glucuronides / Q000652:urine; D006207:Half-Life; D006801:Humans; D008297:Male; D008875:Middle Aged; D012709:Serum Albumin / Q000378:metabolism; D013237:Stereoisomerism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D020719:Glucuronides; D012709:Serum Albumin; D005279:Fenoprofen