Kraul H, Truckenbrodt J, Huster A, Töpfer R, Hoffmann A
Institute of Clinical Pharmacology, Friedrich Schiller University, Jena, FRG.
Eur J Clin Pharmacol. 1991;41(5):475-80. doi: 10.1007/BF00626373.
The activity of 7-ethoxycoumarin O-deethylase (ECOD) has been measured in liver biopsy samples from 23 patients (smokers and non-smokers) with different degrees of structural liver damage. The results, which reflect in vitro cytochrome P450-dependent biotransformation, were correlated with various measures of the P450-dependent in vivo elimination of caffeine and metamizol. The relatively non-specific, low affinity component of ECOD activity was significantly correlated with the kinetics of metamizol (mean residence time, apparent clearance, half-life, area under the concentration-time curve, and metabolite excretion in the urine). Thus, metamizol elimination, which is mainly due to P450 IIB, and the low affinity component of ECOD both reflect, at least in part, the activity of the same form of P450. In contrast, caffeine biotransformation, which is via P450 IA, was not correlated with ECOD activity. There was no relation between the kinetics of metamizol and caffeine, perhaps because of the inducing effect that smoking has on caffeine elimination. In patients with liver disease, smoking appears to alter the elimination of caffeine more than the degree of liver disease.
