PMID: 2051311Feb 1, 1991Paper

Uptake and elution of chlormethiazole, meperidine, and minaxolone in the hindquarters of sheep: implications for clearance calculations

Journal of Pharmaceutical Sciences
R N UptonR J Carapetis


Mass balance principles were used to describe the uptake and elution of chlormethiazole, meperidine, and minaxolone in the hindquarters of sheep. Sheep received a right atrial infusion of either chlormethiazole (3.71 mg/min) or meperidine (2.70 mg/min) for 180 min, or minaxolone (0.37 mg/min) for 120 min. Paired arterial and inferior vena cava (draining the hindquarters) blood samples were taken during and after the infusion. The mean and SD (n = 4) of the time-averaged extraction ratios across the hindquarters (determined from the relevant arterio-venous area under blood concentration--time curves) were 0.12 (0.10), 0.36 (0.13), and 0.27 (0.05) for chlormethiazole, meperidine, and minaxolone, respectively. The rank order of the rate of uptake of the drugs into the hindquarters was the same as the rank order of their lipophilicity, and uptake still continued when both the arterial and inferior vena cava drug concentrations were essentially constant. For chlormethiazole, meperidine, and minaxolone, 48% (44), 4% (6), and 35% (17), respectively, of the drug taken into the hindquarters eluted from the hindquarters after the infusion. Drug uptake and retention in extravisceral tissues, represented here by the hindquarters, can resul...Continue Reading


Jan 1, 1976·Pharmacology & Therapeutics. Part B: General & Systematic Pharmacology·A Junod
Jan 1, 1978·Drug Metabolism Reviews·A PannatierJ C Etter
Nov 1, 1988·Biopharmaceutics & Drug Disposition·A C MacIntyre, D J Cutler
Feb 1, 1988·Journal of Pharmacokinetics and Biopharmaceutics·R N UptonR J Carapetis
Feb 1, 1974·Journal of Pharmaceutical Sciences·L E Mather, G T Tucker
Jan 1, 1980·Pharmacology & Therapeutics·M R Juchau
Mar 1, 1981·European Journal of Clinical Pharmacology·L T SeowJ G Roberts

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