Effect of Renal and Hepatic Insufficiency on the Pharmacokinetics of Betaxolol, A New Adrenergic ß-Blocker

Thiercelin, J. F.; Bianchetti, G.; Padovani, P.; Pl, Morselli; Friès, D; Costa, Josep; Paccalin, J; Bouchet, J L; Martin-Dupont, C

doi:10.1007/978-1-4613-2799-8_50

Cited by 2 publications

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“…For drugs with low extraction including betax-0101, reduced intrinsic clearance would tend to increase the elimination half-life: this has been con-firmed clinically (Thiercelin et al 1984). The kinetics of the hydrophilic drugs atenolol and sotalol are unaffected by liver disease (Sotaniemi et al 1983).…”

Section: Liver Diseasementioning

confidence: 97%

“…Following absorption, lipophilic drugs including alprenolol, labetalol, metoprolol, oxprenolol, propranolol and timolol, and to a lesser extent pindolol and betaxolol (Shanks 1983;Thiercelin et al 1984) [table I] are subject to presystemic elimination. The magnitude of the effect depends on the route and frequency of administration and may also be altered by changes in liver blood flow and liver drug-metabo1ising ability (George 1979).…”

Section: Absorptionmentioning

confidence: 99%

“…Single oral doses of acebutolol administered to patients with impaired renal function have significantly reduced urinary excretion of acebutolol and N-acetyl acebutolol (Ver-312 beeck 1978; Verbeeck et al 1981) and plasma concentrations of the metabolite may be 30 times that of the parent compound (Munn et al 1980). Betaxolol, of which about 15% is excreted unchanged in the urine, has a slightly increased half-life in patients with severely impaired renal function, which is unaffected by haemodialysis or peritoneal dialysis (Thiercelin et al 1984). Metoprolol has 2 active metabolites in humans -O-demethylmetoprolol and a-hydroxymetoprolol (Regardh et al 1974).…”

Section: Renal Diseasementioning

confidence: 99%

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Clinical Pharmacokinetics of ??-Adrenoceptor Antagonists

Riddell¹,

Harron²,

Shanks³

1987

Clinical Pharmacokinetics

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The beta-adrenoceptor antagonists have been widely used clinically for over 20 years and their pharmacokinetics have been more thoroughly investigated than any other group of drugs. Their various lipid solubilities are associated with differences in absorption, distribution and excretion. All are adequately absorbed, and some like atenolol, sotalol and nadolol which are poorly lipid-soluble are excreted unchanged in the urine, accumulating in renal failure but cleared normally in liver disease. The more lipid-soluble drugs are subject to variable metabolism in the liver, which may be influenced by age, phenotype, environment, disease and other drugs, leading to more variable plasma concentrations. Their clearance is reduced in liver disease but is generally unchanged in renal dysfunction. All the beta-adrenoceptor antagonists reduce cardiac output and this may reduce hepatic clearance of highly extracted drugs. In addition, the metabolised drugs compete with other drugs for enzymatic biotransformation and the potential for interaction is great, but because of the high therapeutic index of beta-adrenoceptor antagonists, any unexpected clinical effects are more likely to be due to changes in the kinetics of the other drug. Because satisfactory plasma concentration effect relationships have been difficult to establish for most clinical indications, and little dose-related toxicity is seen, plasma beta-adrenoceptor antagonist concentration measurement is usually unnecessary. The investigation of the clinical pharmacokinetics of the beta-adrenoceptor antagonists has added greatly to our theoretical and practical knowledge of pharmacokinetics and made some contribution to their better clinical use.

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Section: Liver Diseasementioning

confidence: 97%

Section: Absorptionmentioning

confidence: 99%

Section: Renal Diseasementioning

confidence: 99%

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