Effect of some drugs on cat microsomal enzyme

الملخص EN

Inhibitory effects of ketoconazole (KTZ), cimetidine (CIM), and erythromycin (ERY) were examined on CYP3A activities.

Midazolam 1’-and 4-hydroxylation (MDZ1’H and MDZ4H) were used to determine CYP3A activities in hepatic microsomes obtained from cats.

The results showed that, all the examined drugs inhibited the reactions in a noncompetitive manner.

The inhibitory constants (Ki) of KTZ were 2.80 and 115 μM for MDZ1’H and MDZ4H, respectively.

Those of CIM were 3.13 and 3.27 mM and of ERY were 3.14 and 6.41 mM for MDZ1’H and MDZ4H, respectively.

Also, the effects of KTZ and CIM on the pharmacokinetics of quinidine (QUN) were Studied ; KTZ or CIM (10 mg / kg / day, for one week) was given orally to cats.

QUN (2 mg/kg, i.

v.) was injected 2 h after the last dose of KTZ or CIM.

The analysis of the obtained pharmacokinetic parameters showed that, KTZ significantly reduced total body clearance (Cltot) of QUN by about 30 %, while CIM did not.

These results suggest that, KTZ inhibits CYP3A activities (both in vitro and in vivo), but CIM does not.

In clinical practice, therefore, KTZ may result in inhibition based drug-drug interaction with CYP3A substrates in cat, whereas CIM and ERY are unlikely to lead to interaction involving CYP3A substrates.