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): Cmax 14.1 (12.5–15.8) versus 3.6 (2.5–4.7) μg/ml; AUC ss0–8 80.5 (67.3–93.7) versus 12.1 (8.8–15.4) μg·h/ml; ClT/f 1.3 (1.0–1.5) versus 9.1 (6.5–11.8) l/h; and t1/2 3.1 (2.3–3.9) versus 1.2 (0.8–1.6) h. The ClT/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 ClT/f for the (+)‐(S)‐FEN. The lower ClT/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. Chirality 16:602–608, 2004. © 2004 Wiley‐Liss, Inc.