Protein binding and the metabolism of thiamylal enantiomers in vitro.

Article Details


Sueyasu M, Fujito K, Shuto H, Mizokoshi T, Kataoka Y, Oishi R

Protein binding and the metabolism of thiamylal enantiomers in vitro.

Anesth Analg. 2000 Sep;91(3):736-40.

PubMed ID
10960410 [ View in PubMed

Thiamylal, a chiral thiobarbiturate, is marketed as a racemic product. We studied the serum protein binding and microsomal metabolism of thiamylal enantiomers in vitro. The unbound fraction of R(+)-thiamylal was greater than that of S(-)-thiamylal. The analysis of binding data revealed that both enantiomers bound to human serum albumin through only one site. In displacement studies with site-specific probes, dansylsarcosine, but not warfarin, significantly decreased the binding of both enantiomers. The bindings of enantiomers were also decreased by octanoate and a large concentration of oleate. These findings suggest that both enantiomers bind to Site II of albumin with higher affinity for S(-)-enantiomer. R(+)-thiamylal was metabolized more rapidly than S(-)-enantiomer by human liver microsomes. An experiment with isoform-selective inhibitors and cytochrome P-450 (CYP) isoforms showed that CYP2C9 had the highest activity for the metabolism of both enantiomers, the activity being 7 to 10 times that of CYP2E1 and CYP3A4. CYP2C9 showed a significantly rapid metabolism of R(+)-enantiomer, suggesting that CYP2C9 is mainly involved in the enantioselective metabolism of thiamylal. IMPLICATIONS: Because clinically marketed thiamylal is a racemic compound, a pharmacokinetic study of each enantiomer may be beneficial. We found that the enantioselectivity of thiamylal existed in protein binding and metabolism. This may be caused by the differences in the affinities of enantiomers for albumin and cytochrome P-450 isoform.

DrugBank Data that Cites this Article

Drug Enzymes
DrugEnzymeKindOrganismPharmacological ActionActions
ThiamylalCytochrome P450 2C9ProteinHumans
ThiamylalCytochrome P450 3A4ProteinHumans