In vitro assessment of stereoselective hepatic metabolism of disopyramide in humans: Comparison with in vivo data

Corre, Pascal Le; Ratanasavanh, Damrong; Chevanne, François; Gibassier, D; Sado, P. A.; Verge, Roger Le

doi:10.1002/chir.530030505

“…Macrolide antibiotics, particularly erythromycin, can both interfere with disopyramide specificities of the antibodies for the enantiomers of this racemic drug, which exhibits stereoselectivity with respect metabolism and produce additive potassium channel blockade. This form of interaction could lead to lifeto metabolism, renal clearance and protein binding [42]. Interestingly, total clearance of each of the isolated threatening torsades de pointes.…”

Section: Diltiazem Channelmentioning

confidence: 99%

Therapeutic drug monitoring: antiarrhythmic drugs

Campbell

¹

,

Williams

²

2001

Brit J Clinical Pharma

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Antiarrhythmic agents are traditionally classified according to Vaughan Williams into four classes of action. Class I antiarrhythmic agents include most of the drugs traditionally thought of as antiarrhythmics, and have as a common action, blockade of the fast-inward sodium channel on myocardium. These agents have a very significant toxicity, and while they are being used less, therapeutic drug monitoring (TDM) does significantly increase the safety with which they can be administered. Class II agents are antisympathetic drugs, particularly the b-adrenoceptor blockers. These are generally safe agents which do not normally require TDM. Class III antiarrhythmic agents include sotalol and amiodarone. TDM can be useful in the case of amiodarone to monitor compliance and toxicity but is generally of little value for sotalol. Class IV antiarrhythmic drugs are the calcium channel blockers verapamil and diltiazem. These are normally monitored by haemodynamic effects, rather than using TDM. Other agents which do not fall neatly into the Vaughan Williams classification include digoxin and perhexiline. TDM is very useful for monitoring the administration (and particularly the safety) of both of these agents.

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“…Le Corre et al (206) have analyzed stereoselective metabolism of disopyramide in human hepatocyte cultures. The metabolic rate of S(+) disopyramide was 2.5-fold higher than that of R(-) disopyramide.…”

Section: However Survival and Metabolic Compe-mentioning

confidence: 99%

Liver cell models in in vitro toxicology.

Guillouzo

¹

1998

Environ Health Perspect

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In vitro liver preparations are increasingly used for the study of hepatotoxicity of chemicals. In recent years their actual advantages and limitations have been better defined. The cell models, slices, and mainly primary hepatocyte cultures, appear to be the most powerful in vitro systems, as liver-specific functions and responsiveness to inducers are retained either for a few days or several weeks depending on culture conditions. Maintenance of phase and phase 11 xenobiotic metabolizing enzyme activities allows various chemical investigations to be performed, including determination of kinetic parameters, metabolic profile, interspecies comparison, inhibition and induction effects, and drug-drug interactions. In vitro liver cell models also have various applications in toxicology: screening of cytotoxic and genotoxic compounds, evaluation of chemoprotective agents, and determination of characteristic liver lesions and associated biochemical mechanisms induced by toxic compounds. Extrapolation of the results to the in vivo situation remains a matter of debate. Presently, the most convincing applications of liver cell models are the studies on different aspects of metabolism and mechanisms of toxicity. For the future, there is a need for better culture conditions and differentiated hepatocyte cell lines to overcome the limited availability of human liver tissues. In addition, strategies for in vitro analysis of potentially toxic chemicals must be better defined. Environ Health Perspect 106(Suppl 2):511-532 (1998). http.//ehpnetl.niehs.nih.gov/docs/1998/Suppl-2/51 1-532guillouzo/abstract.html

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“…Macrolide antibiotics, particularly erythromycin, can both interfere with disopyramide specificities of the antibodies for the enantiomers of this racemic drug, which exhibits stereoselectivity with respect metabolism and produce additive potassium channel blockade. This form of interaction could lead to life-to metabolism, renal clearance and protein binding [42]. Interestingly, total clearance of each of the isolated threatening torsades de pointes.…”

Section: Diltiazem Channelmentioning

confidence: 99%

Therapeutic drug monitoring: antiarrhythmic drugs

Campbell¹,

Williams²

2001

Br J Clin Pharmacol

View full text Add to dashboard Cite

Antiarrhythmic agents are traditionally classified according to Vaughan Williams into four classes of action. Class I antiarrhythmic agents include most of the drugs traditionally thought of as antiarrhythmics, and have as a common action, blockade of the fast-inward sodium channel on myocardium. These agents have a very significant toxicity, and while they are being used less, therapeutic drug monitoring (TDM) does significantly increase the safety with which they can be administered. Class II agents are antisympathetic drugs, particularly the b-adrenoceptor blockers. These are generally safe agents which do not normally require TDM. Class III antiarrhythmic agents include sotalol and amiodarone. TDM can be useful in the case of amiodarone to monitor compliance and toxicity but is generally of little value for sotalol. Class IV antiarrhythmic drugs are the calcium channel blockers verapamil and diltiazem. These are normally monitored by haemodynamic effects, rather than using TDM. Other agents which do not fall neatly into the Vaughan Williams classification include digoxin and perhexiline. TDM is very useful for monitoring the administration (and particularly the safety) of both of these agents.

show abstract

In vitro assessment of stereoselective hepatic metabolism of disopyramide in humans: Comparison with in vivo data

Cited by 9 publications

References 20 publications

Therapeutic drug monitoring: antiarrhythmic drugs

Therapeutic drug monitoring: antiarrhythmic drugs

Liver cell models in in vitro toxicology.

Therapeutic drug monitoring: antiarrhythmic drugs

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