Pharmacokinetics of naproxen in Bangladeshi type II diabetic patients treated with gliclazide

Abstract

This study was aimed to investigate pharmacokinetics of naproxen in Bangladeshi type II diabetic subjects treated with gliclazide. All the subjects were divided into three groups; group G, diabetic subjects only took gliclazide in the first session, GN/NG group diabetic subjects took both gliclazide and naproxen in the second session and N group, healthy subjects only took naproxen in the 3rd session.Glucose solution with breakfast was served at 2.0 h, a standard lunch was served at 5.0 h and snacks was served at 8h after dosing in every session. Blood samples were collected for 24.0 h after drug administration. Drug plasma concentrations were determined by HPLC with a UV detector. Analysis of pharmacokinetic characteristics was based on a non-compartmental model. Pharmacokinetic parameters for single oral dose naproxen are Cmax, AUC0-∞, AUC0-24, Tmax, T1/2 and Kel were 65.33μg./mL-1, 926.68 μg.h.mL-1, 856.25 μg.h.mL-1, 0.93h, 10.07h and 0.07 respectively. In case of concurrent administration of naproxen and gliclazide, Cmax, AUC0-∞, AUC0-24, Tmax, T1/2 and Kel values for naproxen were 58.37 μg./mL-1, 889.57μg.h.mL-1, 819.76μg.h.mL-1, 1.04 h, 10.61h and 0.069 respectively. Likewise, for single dose oral gliclazide tablet, Cmax, AUC0-∞, AUC0-24, Tmax, T1/2 and Kel values were 4.07μg./mL-1, 64.39 μg.h.mL-1, 57.59μg.h.mL-1, 3.58 h, 7.073h and 0.099 respectively. However, in presence of naproxen Cmax, AUC0-∞, AUC0-24, Tmax, T1/2 and Kel values of gliclazide were 3.58μg./mL-1, 79.94μg.h.mL-1, 70.38μg.h.mL-1, 4.02 h, 8.64h and 0.078 respectively. Over all the pharmacokinetic parameters, naproxen shows no significant change in its pharmacokinetics in presence of gliclazide. Although, AUC change was to some extent considerable. Presumably, it is due to healthy vs diabetic subjects comparison. However, Gliclazide pharmacokinetics alteration was surprisingly significant. AUC (p˂0.056*, p˂0.048*), Cmax (p˂0.007**) and T1/2 (p< 0.054*) have been considerably changed in presence of naproxen.