59826-22-1Relevant articles and documents
Involvement of CYP2D1 in the metabolism of carteolol by male rat liver microsomes
Umehara,Kudo,Odomi
, p. 1121 - 1129 (1997)
1. The metabolism of carteolol, a β-adrenoceptor blocking drug, was investigated in male Sprague-Dawley rat liver microsomes. 2. The formation of 8-hydroxycarteolol was the principal metabolic pathway of carteolol in vitro and followed Michaelis-Menten kinetics with a K(m) = 11·0 ± 5·4 μM and a V(max) = 1·58 ± 0·64 nmol/min/nmol P450 respectively (mean ± SD, n = 5). Eadie-Hofstee plot analysis of carteolol 8-hydroxylase activity confirmed single-enzyme Michaelis-Menten kinetics. 3. The cytochrome P450 isoforms involved in 8-hydroxylation of carteolol were investigated using selective chemical inhibitors and polyclonal anti-P450 antibodies. Quinine (K(i) = 0·06 μM)) and quinidine (K(i) = 2·0 μM)), selective inhibitors of CYP2D1, competitively inhibited 8-hydroxycarteolol formation. Furthermore, only anti-human CYP2D6 antibody inhibited this reaction. 4. These results suggest that carteolol is metabolized to 8-hydroxycarteolol by CYP2D1. The K(m) of carteolol for CYP2D1 in male rat liver microsomes was much greater than these of propranolol or bunitrolol, indicating that carteolol has a lower affinity for CYP2D1 compared with these other β-adrenoceptor blocking drugs.
