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 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.
Poggi
Josiane Cristófani
JC
Faculdade de Ciências Farmacêuticas de Ribeirão Preto-USP, Departamento de Física e Química, Avenida do Café s.n. Campus da USP, 14040-903. Ribeirão Preto, São Paulo, Brazil. mldreis@fcfrp.usp.br
Barissa
Giuliano Rodrigo
GR
Donadi
Eduardo Antônio
EA
Foss
Milton Cesar
MC
Cunha
Fernando de Queiróz
FQ
Lanchote
Vera Lucia
VL
dos Reis
Marina Lemos
ML
D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000493:pharmacokinetics*; D003920:Diabetes Mellitus / Q000378:metabolism*; D005260:Female; D005279:Fenoprofen / Q000493:pharmacokinetics*; D006801:Humans; D008297:Male; D008875:Middle Aged
D000894:Anti-Inflammatory Agents, Non-Steroidal; D005279:Fenoprofen