KINETIC-ANALYSIS OF MUTUAL METABOLIC INHIBITION OF LIDOCAINE AND PROPRANOLOL IN RAT-LIVER MICROSOMES

The metabolic interaction between lidocaine (LD) and propranolol (PL) was analysed kinetically in rat liver microsomes. Employing a very sho rt incubation time of 30 sec, we demonstrated that PL competitively in hibited liver microsomal 3-hydroxylation of LD, but did not affect eit her the formation of monoethylglycinexylidide or methylhydroxylidocain e from LD in PL concentrations up to 1 muM. On the other hand, LD comp etitively inhibited PL 4-, 5- and 7-hydroxylations, but the inhibition type of LD for PL N-desisopropylation could not be clarified. Compari son of the kinetic data for liver microsomes from Wistar and Dark Agou ti rats indicated that among the primary metabolic pathways of LD, the V(max) value for 3-hydroxylation was markedly less in female Dark Ago uti rats. The results suggest that LD 3-hydroxylation and PL ring hydr oxylations are mediated by the same isozyme(s) belonging to the CYP2D subfamily.