HEPATIC UPTAKE OF PROPRANOLOL

  • 1 January 1978
    • journal article
    • research article
    • Vol. 206  (1) , 172-180
Abstract
Isolated rat livers were perfused with propranolol and other drugs in a simplified recirculation system without plasma proteins or erythrocytes. The propranolol levels in the reservoir declined biphasically. The 1st phase was rapid and almost flow-limited despite use of high perfusion flow rates. This rapid uptake generated liver/perfusate ratios greater than 25 and was not significantly diminished by lowering the temperature or removing O2 from the system. It appeared to reflect one or more physical binding processes. Autoradiography showed high concentrations of propranolol in the periportal zones of the liver lobule. The 2nd, slower phase of uptake was associated with metabolism of propranolol to other compounds and was temperature, O2 and concentration dependent. A number of drugs inhibited the slow phase but had little effect on the rapid uptake phase. Several of these drugs were able to displace small amounts of propranolol from the liver.

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