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  • Title: Pharmacokinetic modelling of the effect of activated charcoal on the intestinal secretion of theophylline, using the isolated vascularly perfused rat small intestine.
    Author: de Vries MH, Rademaker CM, Geerlings C, Van Dijk A, Noordhoek J.
    Journal: J Pharm Pharmacol; 1989 Aug; 41(8):528-33. PubMed ID: 2571696.
    Abstract:
    The effect of activated charcoal administration on the secretion of theophylline from the blood into the intestinal lumen has been examined by use of the rat isolated vascularly perfused small intestine. A closed two compartment model was used to analyse the vascular and luminal concentration-time curves obtained. An equation was derived to calculate the time-dependent intestinal clearance. From control experiments it was concluded that theophylline is secreted by a diffusional transport system through the intestinal wall. The intestinal clearance declined rapidly with time as a result of the concomitant increase in luminal theophylline concentration. After 120 min a steady state between the vascular and luminal perfusate was established. Administration of activated charcoal in the lumen had a profound effect on the kinetics of the drug. The vascular steady state concentration was depressed dramatically. The theophylline clearance remained nearly constant with time, because the blood to lumen concentration gradient was maximized. The maximal value for the intestinal theophylline clearance was estimated to be 0.88 mL min-1 and it equalled the value for the intestinal blood flow at the absorptive site. By use of the concept of absorptive site blood flow, the maximal effect of charcoal on systemic theophylline clearance could be adequately predicted for rats, dogs and man. Activated charcoal administration is only useful to enhance the systemic clearance of drugs or toxicants if that clearance is of the same order of magnitude as the absorptive site blood flow or lower.
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