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Pharmacodynamics, Chiral Pharmacokinetics, and Pharmacokinetic‐Pharmacodynamic Modeling of Fenoprofen in Patients With Diabetes Mellitus

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 μg·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 μg/mL) and γ (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.