Lidocaine uptake in isolated rat hepatocytes and effects of dl-propranolol

Chen, Chi-Po; Vu, Van Tien; Cohen, Steven D.

doi:10.1016/0041-008x(80)90232-x

Cited by 12 publications

(3 citation statements)

References 13 publications

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“…This observation has prompted further studies of the ability of 83-adrenoceptor blockers to inhibit the intrinsic oxidative metabolism of drugs (Bax et al, 1983 , 1982;Deacon etal., 1981). This observation, and the results of others which showed an inhibitory effect of propranolol on the uptake and elimination of lignocaine by isolated rat hepatocytes and by isolated livers perfused at a constant flow (Chen et al, 1980, Vu & Chen, 1982, are prerequisite to a complete understanding of the interaction between 83-adrenoceptor blockers and lignocaine in man. Thus, a decrease in intrinsic clearance caused by lipid-soluble f3-adrenoceptor blockers should augment any haemodynamic effects of these drugs on lignocaine clearance (see Appendix).…”

Section: Intrinsic Clearancementioning

confidence: 99%

Effects of beta‐adrenoceptor antagonists on the pharmacokinetics of lignocaine.

Tucker¹,

Bax²,

Lennard³

et al. 1984

Brit J Clinical Pharma

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1 In theory, 3-adrenoceptor antagonists could lower the clearance of free lignocaine in three ways (a) by decreasing hepatic blood flow, (b) by competing for plasma binding sites or (c) by inhibiting the enzymes responsible for metabolising lignocaine. 2 The first mechanism has been demonstrated for propranolol and is probably common to all agents lacking intrinsic sympathomimetic activity.3 The second mechanism is discounted by data showing that propranolol, one of the more highly bound f8-adrenoceptor antagonists, does not alter the free fraction of lignocaine in plasma.4 In vitro studies support the third mechanism for the more lipid-soluble ,8-adrenoceptor antagonists, as does the fact that observed decreases in the clearance of lignocaine in vivo are generally greater than the anticipated maximum lowering of hepatic blood flow.

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Section: Intrinsic Clearancementioning

confidence: 99%

Effects of beta‐adrenoceptor antagonists on the pharmacokinetics of lignocaine.

Tucker¹,

Bax²,

Lennard³

et al. 1984

Brit J Clinical Pharma

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“…A h-blocker, propranolol, was reported to prolong the elimination half-life of lidocaine in dog and man (Oda et al, 1989;Ochs et al, 1980), this effect being attributed to a reduction in cardiac output and, therefore, hepatic blood flow due to propranolol-induced h-blockade. Chen et al reported a probable drug interaction between lidocaine and propranolol at common binding sites in isolated rat hepatocytes (Chen et al, 1980). Conrad et al suggested that a large part of the effect of propranolol on lidocaine elimination is a direct effect of the drug or its metabolites on the hepatic uptake of lidocaine or on inhibition of hepatic oxidative enzymes (Conrad et al, 1983).…”

Section: Discussionmentioning

confidence: 98%

“…Whether propranolol reduces the clearance of the local anesthetic agents is unknown. Propranolol interferes with drug metabolism within the hepatocyte (Conrad et al, 1983;Chen et al, 1980). Lidocaine is avidly metabolized by mammalian liver and extrahepatic tissues (Benowitz and Meister, 1978;Oda et al, 1989) and cytochromes P-450 2B1, P-450 4B1 and P-450 3A4 in microsomes contribute to the metabolism of lidocaine to a monoethylglycinexylidide and 3-hydroxy lidocaine (Bargetzi et al, 1989;Oda et al, 1989).…”

Section: Introductionmentioning

confidence: 94%

Porcine FAD-containing monooxygenase metabolizes lidocaine, bupivacaine and propranolol in vitro

Liao

Tomita

et al. 2004

Life Sciences

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The potential role of lysosomes in tissue distribution of weak bases

Macintyre

Cutler

1988

Biopharm & Drug Disp

190

114

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The potential importance of lysosomes as a site of accumulation of weak bases in tissues is discussed. A simple mathematical treatment predicts the quantitative significance of lysosomal trapping for monoacidic and diacidic weak bases.The features which are characteristics of lysosomal trapping are discussed, particularly in comparison with active transport and intracellular binding mechanisms. These features include: linear accumulation at low concentrations; nonlinearity at higher concentrations; dependence on structural integrity of tissue; energy dependence and competition with other weak bases. Subcellular distribution studies have previously shown that weak bases accumulate extensively in membranes; however, the dependence of accumulation on the structural integrity of tissue suggests that this is not the only significant mechanism of accumulation.The results of a range of studies of tissue distribution of weak bases are discussed to illustrate that these findings are consistent with accumulation in lung and liver being attributable to a combination of lysosomal trapping and accumulation in membranes whereas, in muscle, accumulation in membranes is the predominant mechanism of accumulation. The possible pharmacokinetic significance of lysosomal trapping of weak bases is also discussed.

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Lidocaine uptake in isolated rat hepatocytes and effects of dl-propranolol

Cited by 12 publications

References 13 publications

Effects of beta‐adrenoceptor antagonists on the pharmacokinetics of lignocaine.

Effects of beta‐adrenoceptor antagonists on the pharmacokinetics of lignocaine.

Porcine FAD-containing monooxygenase metabolizes lidocaine, bupivacaine and propranolol in vitro

The potential role of lysosomes in tissue distribution of weak bases

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