Fatal aplastic anaemia associated with clopidogrel.

Clopidogrel, an inhibitor of platelet aggregation, was initially thought to be free of the side-effects of ticlopidine. We describe a man who developed aplastic anaemia after 5 months of treatment with clopidogrel. There were no other plausible causes.

Antioxidant defence capacity modulation of two human cell lines by amiodarone and desethylamiodarone.

Although the role of oxidative stress has recently been the subject of increased discussion in relation to the pathogenesis of amiodarone (AMIO) toxicity, the cellular mechanisms underlying the hepatic and pulmonary disorders remain unknown. In order to investigate the effects of AMIO and its active metabolite desethylamiodarone (DEA) on the cellular antioxidant status, defence capacities of liver and lung cell lines have been first compared with published data on normal corresponding cells. Glutathione content, superoxide dismutase (SOD) and glutathione-related enzymes were then determined in Hep 3B and L132 cells, after AMIO and DEA treatment.

Amiodarone N-deethylation in human liver microsomes: involvement of cytochrome P450 3A enzymes (first report).

Experiments were conducted on three different human liver samples to identify the cytochrome P450 isozyme which is involved in the biotransformation of the class III antiarrhythmic agent, amiodarone, into its major metabolite, desethylamiodarone (DEA). The classic P450 inhibitors, SKF 525A, metyrapone, and carbon monoxide provided a significant reduction in the in vitro formation of DEA by human hepatic microsomes. Amiodarone N-deethylase activities expressed by intrinsic clearance values were similar in all the livers used, although two livers were genotyped as extensive and one as a poor metabolizer for the cytochrome P450 CYP2D6 gene.

High-performance liquid chromatographic assay for amiodarone N-deethylation in microsomes of rat liver.

A reversed-phase high-performance liquid chromatographic assay using ultraviolet detection is described for determining the production of the major N-dealkylated metabolite of amiodarone in rat liver microsomes. The principal advantages of this method are its simple sample preparation (protein precipitation by acetonitrile), low detection limit for N-desethylamiodarone (0.05 mumol/l) and relatively short analysis time (16 min).

Age-correlated modifications of copper-zinc superoxide dismutase and glutathione-related enzyme activities in human erythrocytes.

To obtain a comprehensive profile of the erythrocyte antioxidant defense potential during aging, we investigated copper-zinc superoxide dismutase (CuZn-SOD), seleno-dependent glutathione peroxidase (GSH-Px), glutathione reductase (GSSG-RD), and glutathione-S-transferase (GSH-S-T) activities in human erythrocytes from 167 apparently healthy subjects, ages one month to 63 years (102 females, 65 males). We found a negative correlation between age and activities of CuZn-SOD (r = 0.362, P less than 0.