Document Detail

Interaction between amiodarone and lidocaine.
MedLine Citation:
PMID:  8891878     Owner:  NLM     Status:  MEDLINE    
We investigated the in vitro and in vivo interaction between amiodarone and lidocaine. The interaction on a molecular level was first studied in microsomes from 11 human livers. Close correlations between amiodarone N-monodesethylase activities and (a) the amounts of cytochrome P-4503A4 (CYP3A4), and (b) the rates of lidocaine N-monodesethylation were observed. Lidocaine inhibited amiodarone N-monodesethylation (Ki = 120 microM) competitively; inversely, amiodarone suppressed lidocaine N-monodesethylase activity in the same manner (Ki = 47 microM). Moreover, the metabolite N-monodesethylamiodarone (DEA) was stable and inhibited lidocaine metabolism in a concentration-dependent manner. The in vivo interaction was investigated in 6 cardiac patients. Each of them received a dose of 1 mg/kg lidocaine hydrochloride intravenously (i.v.) on three different occasions: before amiodarone treatment (control), and after cumulative doses of 3 g (phase I) and 13 g (phase II), respectively, amiodarone hydrochloride. The analysis of lidocaine pharmacokinetics showed an increase in lidocaine area under the curve (AUC) when amiodarone was administered, whereas that of N-monodesethylated lidocaine decreased. Moreover, the systemic clearance of lidocaine decreased, while the elimination half-life (t1/2) and the distribution volume at steady state of lidocaine remained unchanged. The pharmacokinetic parameters during phase II were the same as those during phase 1, indicating that the interaction had already occurred early in the loading phase of amiodarone administration. The interaction between amiodarone and lidocaine may be explained by the inhibition of CYP3A4 by amiodarone and/or by its main metabolite DEA.
H R Ha; R Candinas; B Stieger; U A Meyer; F Follath
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Publication Detail:
Type:  Clinical Trial; In Vitro; Journal Article    
Journal Detail:
Title:  Journal of cardiovascular pharmacology     Volume:  28     ISSN:  0160-2446     ISO Abbreviation:  J. Cardiovasc. Pharmacol.     Publication Date:  1996 Oct 
Date Detail:
Created Date:  1997-03-24     Completed Date:  1997-03-24     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  7902492     Medline TA:  J Cardiovasc Pharmacol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  533-9     Citation Subset:  IM    
Cardiovascular Therapy Research Unit, University Hospital, Zurich, Switzerland.
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MeSH Terms
Amiodarone / administration & dosage,  pharmacokinetics,  pharmacology*
Anti-Arrhythmia Agents / pharmacokinetics,  pharmacology*
Arrhythmias, Cardiac / drug therapy
Blood Proteins / metabolism
Cytochrome P-450 CYP3A
Cytochrome P-450 Enzyme System / metabolism
Drug Interactions
Drug Therapy, Combination
Lidocaine / administration & dosage,  pharmacokinetics,  pharmacology*
Microsomes, Liver / drug effects,  enzymology
Middle Aged
Mixed Function Oxygenases / metabolism
Protein Binding
Reg. No./Substance:
0/Anti-Arrhythmia Agents; 0/Blood Proteins; 137-58-6/Lidocaine; 1951-25-3/Amiodarone; 9035-51-2/Cytochrome P-450 Enzyme System; EC 1.-/Mixed Function Oxygenases; EC protein, human; EC protein, human; EC P-450 CYP3A

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