Reduction in Lidocaine Clearance during Continuous Infusion and by Coadministration of Propranolol

Section: Discussionsupporting

confidence: 91%

Penbutolol and propranolol: a comparison of their effects on antipyrine clearance in man.

Bax¹,

Jones²,

Lennard³

et al. 1985

“…Such changes may be related in part to changes in tissue distribution and to reduced free clearance of this 'high clearance' drug caused by an increase in plasma protein binding. Nevertheless, the free plasma lignocaine concentration does increase slightly (although to a much smaller extent than total plasma and whole blood concentrations) and this has been explained by a time-dependent fall in intrinsic free clearance of drug which has been seen in normal volunteers after prolonged lignocaine administration (Ochs et al, 1980). More than one phenomenon, therefore, appears to be occurring in this situation.…”

Section: Antiarrhythmicsmentioning

confidence: 97%

The plasma protein binding of basic drugs.

Routledge¹

1986

167

The plasma protein binding of basic drugs appears to vary more than was at first assumed and is related to the marked intra‐and interindividual differences in one of the chief binding proteins, AAG. Changes in AAG concentrations will result in alterations in the distribution and metabolism of basic drugs which will complicate the interpretation of the relationship between total drug concentration and drug efficacy or toxicity. For some drugs, e.g. lignocaine, direct measurement of free concentrations may improve their clinical use but rapid and reliable techniques are as yet not readily available.

“…Consistent with these effects in vitro, there is some evidence that certain 1-adrenoceptor blockers may be inhibitors of oxidative drug metabolism in man. Propranolol coadministration has been shown to inhibit the elimination of antipyrine Bax et al, 1981), chlorpromazine (Peet et al, 1980), lignocaine (Ochs et al, 1980;Conrad et al, 1983) and theophylline (Conrad & Nyman, 1980). Similarly, metoprolol has been reported to reduce the clearance of antipyrine and lignocaine (Conrad et al, 1983), although the reduction in the clearances of these drugs was generally only approximately half that following propranolol pretreatment.…”

Section: Introductionmentioning

confidence: 99%

Failure of ‘therapeutic’ doses of beta‐adrenoceptor antagonists to alter the disposition of tolbutamide and lignocaine.

Miners¹,

Wing²,

Lillywhite³

et al. 1984

The effects of separate 1 week pre‐treatments with each of the beta‐ adrenoceptor antagonists, propranolol (80 mg every 12 h), metoprolol (100 mg every 12 h) and atenolol (50 mg once daily), on the disposition of a single i.v. dose of tolbutamide were studied in six healthy volunteers. In addition, the effects of a 1 week pre‐treatment with metoprolol (100 mg every 12 h) and atenolol (50 mg once daily) on the disposition of orally and i.v. administered lignocaine were determined in seven healthy subjects. Tolbutamide clearance, half‐life, volume of distribution and plasma protein binding were not altered by the beta‐ adrenoceptor blocker pre‐treatments. Similarly, neither metoprolol nor atenolol had a significant effect on the systemic clearance, apparent oral clearance or other dispositional parameters of lignocaine. ‘Therapeutic’ plasma concentrations of the beta‐adrenoceptor blockers were confirmed on each study day. It is concluded that the inhibition of oxidative drug metabolism previously reported for lipophilic beta‐ adrenoceptor blockers may be selective for different forms of cytochrome P450 and possible concentration‐dependent.