Effect of Probenecid on the Pharmacokinetic Behavior of Pranoprofen in Rats

The purpose of this study was to investigate the effect of probencid on the pharmacokinetics of oral pranoprofen in rats. Pranoprofen (5 mg/kg) was coadministered with 5, 10 or 20 mg/kg of probenecid orally. Coadministration of probenecid significantly altered the pharmacokinetics of pranoprofen at 10 and 20 mg/kg. Compared with the control group, probenecid significantly (p<0.05) increased the absorption rate constant $(K_{a})$, the peak concentrations $(C_{max})$ and accordingly the area under the plasma concentration-time curve (AUC) of pranoprofen at the dose level of 10 mg/kg and 20 mg/kg of probenecid. The relative bioavailability (RB%) of pranoprofen was 1.64- to 1.82- fold increased. Furthermore, 10 and 20 mg/kg probenecid induced the decreased elimination constants $(K_{el})$ and the prolonged half-lives $(t_{1/2})$ of pranoprofen with significance (p<0.05). Coadministration of 10 and 20 mg/kg of probenecid lowered the excreted amounts of pranoprofen in the urine by 21.3-22.5% compared to the control. Overall, probenecid enhanced the bioavailability of pranoprofen and decreased its elimination rate to a greater degree at higher dose. Based on the effect of probenecid on the pharmacokinetic behavior of pranoprofen, the dosage regimen of pranoprofen should be taken into consideration when pranoprofen is administered with probenecid in the clinical setting to the patients especially with peptic ulcer or renal failure.

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