Effects of Piroxicam on Pharmacodynamics and Pharmacokinetics of Nifedipine in Spontaneously Hypertensive Rats

피록시캄이 니페디핀의 약력학 및 약동학에 미치는 영향

Because nonsteroidal anti-inflammatory drugs are reported to cause fluid retention and hypertension by inhibition of prostaglandin synthesis, the effects of piroxicam on pharmacodynamics and pharmacokinetics of nifedipine were studied in male spontaneously hypertensive rats. They received nifedipine (0.5 mg/kg) alone or combined with piroxicam (5 mg/kg) intravenously. Plasma levels norepinephrine, an index of sympathetic stimulation, were measured prior to each treatment and 5 min after drug administration. Changes in blood pressure were examined serially and blood samples for analysis of nifedipine were also taken for 6 hr following drug administration. Plasma nifedipine concentration were assayed by HPLC and pharmacokinetic parameters were calculated. Blood pressure was reduced (p<0.01), but plasma norepinephrine level was increased (p<0.05) by nifedipine administration. Anti-hypertensive effect of nifedipine was potentiated (p<0.05) by piroxicam coadministration, but effect of nifedipine on plasma norepinephrine level was not affected. In case of rats received nifedipine and piroxicam, plasma nifedipine concentrations were higher (p<0.05) than those from rats received nifedipine alone at 2,3,4,5 and 6 hours following drug administration. The area under the plasma concentration vs. time curve was increased (p<0.05), while the elimination rate constant was decreased (p<0.01) by piroxicam coadministration. No significant differences were observed in the plasma clearance, apparent volume of distribution and elimination half-life. Thus, piroxicam not only potentiated antihypertensive effect of nifedipine, but also altered nifedipine pharmacokinetics in the rats. It is concluded that the potentiation of nifedipine antihypertensive effect might correlate with the increment of its plasma concentration by piroxicam coadministration.