Concentration-dependent Exsorption of Quinidine in the Rat Intestine
- 1 August 1992
- journal article
- Published by Oxford University Press (OUP) in Journal of Pharmacy and Pharmacology
- Vol. 44 (8) , 659-662
- https://doi.org/10.1111/j.2042-7158.1992.tb05489.x
Abstract
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 CLi of quinidine was therefore much higher than the rate of luminal perfusion. Over the infusion dose range of 0·1–2 mg h−1, the CLi of quinidine decreased with increasing plasma concentration of quinidine. Adding quinidine into the luminal perfusate had little effect on the CLi of quinidine. Co-administration of quinidine with other agents intravenously did not alter the CLi of salicylic acid and urea, while the same treatment decreased the CLi of 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−1 of 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.Keywords
Funding Information
- National Sciences Council, Republic of China (NSC79-0412-9006-05, NSC80-0412-B006-22)
This publication has 17 references indexed in Scilit:
- Effect of Theophylline on the Intestinal Clearance of Drugs in RatsJournal of Pharmacy and Pharmacology, 1992
- Role of unstirred water layer in the exsorption of quinidineJournal of Pharmacy and Pharmacology, 1990
- Comparative Drug Exsorption in the Perfused Rat IntestineJournal of Pharmacy and Pharmacology, 1990
- Stereoselective Gastrointestinal Clearance of Disopyramide in Rabbits Treated with Activated CharcoalJournal of Pharmaceutical Sciences, 1988
- Effects of Phenothiazine Derivatives on the Microclimate-pH in the Rat JejunumJournal of Pharmaceutical Sciences, 1988
- Enhancement of Xenobiotic Elimination: Role of Intestinal ExcretionDrug Metabolism Reviews, 1984
- Elimination of Drugs by Passive Diffusion from Blood to Intestinal Lumen: Factors Influencing Nonbiliary Excretion by the Intestinal TractDrug Metabolism Reviews, 1983
- Gastrointestinal Clearance of Drugs with Activated CharcoalNew England Journal of Medicine, 1982
- The magnitude and distribution of the acid microclimate in proximal jejunum and its relation to luminal acidificationProceedings of the Royal Society of London. B. Biological Sciences, 1978
- Direct measurement by pH-microelectrode of the pH microclimate in rat proximal jejunumProceedings of the Royal Society of London. B. Biological Sciences, 1975