| Autor: |
Bair, Chi-Horng, Tang, Ming-Jer, Huang, Jin-Ding |
| Zdroj: |
Journal of Pharmacy and Pharmacology; August 1992, Vol. 44 Issue: 8 p659-662, 4p |
| Abstrakt: |
During intravenous infusion, the luminal concentration of quinidine was higher than the plasma concentration. The intestinal clearance (CLi) of the drug was measured by dividing the rate of appearance of the drug in the intestinal luminal perfusate by the plasma concentration. The CLiof quinidine was therefore much higher than the rate of luminal perfusion. Over the infusion dose range of 0·1–2 mg h−1, the CLiof quinidine decreased with increasing plasma concentration of quinidine. Adding quinidine into the luminal perfusate had little effect on the CLiof quinidine. Co-administration of quinidine with other agents intravenously did not alter the CLiof salicylic acid and urea, while the same treatment decreased the CLiof theophylline and 5-disopyramide. In-vitro experiments on brush-border membrane vesicles showed that quinidine decreased the rate of Na+uptake and H+efflux. The inhibition was significant at quinidine concentrations above 20 μm. Quinidine was a more potent inhibitor than amiloride. At quinidine infusion rates less than 2 mg h−1, quinidine concentration in plasma or in the luminal perfusate was at the lower limit of the inhibitory concentration. Microclimate pH at the intestinal surface was also measured. At mid-jejunum, the microclimate pH increased 0·3 pH units by infusing 2 mg h−1of quinidine, while the microclimate pH at most other measuring sites was not significantly altered by quinidine infusion. It was concluded that quinidine is exsorbed from blood into the intestinal lumen by a carrier-mediated pathway in addition to the passive diffusion. At high plasma concentration, quinidine exsorption becomes saturated. Quinidine inhibited the intestinal exsorption of theophylline and S-disopyramide possibly by competition on the carrier. |
| Databáze: |
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