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The objective of the present study was to assess the influence of type 1 and type 2 diabetes mellitus on the enantioselective pharmacodynamics and pharmacokinetics of fenoprofen. Patients with diabetes mellitus type 1 (n = 7) or type 2 (n = 7) and healthy volunteers (n = 13) received orally a single 600-mg dose of racemic fenoprofen. Monocompartmental analysis of (+)-(S)-fenoprofen showed a significant difference (P < .05, Kruskal-Wallis test) in area under the curve (AUC) values (153.68 vs 243.50 microg x h/mL) and oral clearance (1.95 vs 1.23 L/h) only between patients with diabetes mellitus type 2 and healthy volunteers. The inhibitory activity of cyclooxygenases was evaluated indirectly by the determination of prostaglandin E2 (COX-2) and thromboxane B2 (COX-1) using the sigmoidal inhibitory Emax model. The patients with type 2 diabetes mellitus presented lower IC50 (3.29 vs 6.0 microg/mL) and g (0.73 vs 2.01) values for COX-1 activity compared to healthy volunteers (P < .05, Kruskal-Wallis test). These results show that diabetes mellitus type 2, but not type 1, influences the pharmacokinetics and pharmacodynamics of (+)-(S)-fenoprofen.