Amiodarone-induced alterations in alkaline phosphatase activity in vivo and in vitro

Amiodarone (AD), an antiarrythmic agent, has previously been found to cause gastrointestinal disturbances in patients treated for cardiac arrhythmias. These may be due to the altered activities of intestinal enzymes. We have investigated the effect of AD on alkaline phosphatase (ALP), a critical int estinal enzyme, in vivo and in vitro. In the in vivo experiment, Group 1 an imals served as controls and groups 2, 3, 4 and 5 received 25, 50, 100 and 175 mg of AD/kg body weight/day, orally, for 21 days. Intestinal ALP activi ty was considerably lower in animals treated with 175 mg of AD as compared with the controls. In the in vitro study, ALP was incubated with different concentrations of AD at different substrate concentrations. Binding of AD w ith ALP was determined by equilibrium dialysis. The percent inhibition of A LP activity decreased with increasing substrate concentrations. There are t wo possible reasons for the altered activity of ALP : (1) modification of t he active site of ALP by free radicals produced by AD; and/or (2) direct bi nding of AD with ALP. Thus the altered ALP activity may affect its function in the gastrointestinal tract of AD-treated patients. Med Sci Res 27:233-2 35 (C) 1999 Lippincott Williams & Wilkins.