Drug-induced changes in serum alkaline phosphatase and alanine aminotransferase activities not related to hepatic injuries.

Changes in serum alkaline phosphatase (SAP) and alanine aminotransferase activities are of clinical diagnostic significance in determining hepatic injuries. Drugs, however, can alter the activities of these enzymes by various mechanisms. Phenobarbital increases SAP activity in dogs as a result of hepatic microsomal induction (Litchfield and Corning, 1971). We examined the effect of related enzyme inducers. Beagle dogs (2/sex/group) were dosed orally with phenobarbital or diphenylhydantoin at 40 mg/kg or primidone at 40 to 80 mg/kg for 7 weeks. Only phenobarbital increased SAP; bromsulfophthalein retention was not affected. Plasma antipyrine half-life decreased and liver cytochrome P-450 content increased in each group compared with values from a control group. No histological changes of the liver were seen. Data indicate the specificity of phenobarbital. Some drugs decrease serum enzyme activities, e.g., alanine aminotransferase activity. Cefazolin was given s.c. to rats at 2 g/kg/day on days 1–18 and at 0.5 g/kg/day on days 19–32. Isoniazid was given orally at 20 mg/kg/day for 33 days to a similar group. Half of each group received pyridoxal HCl s.c. at 0.2 mg/ kg/day on days 1–18 and at 2 mg/kg/day on days 19–46. Serum alanine aminotransferase decreased in each group, but returned to normal on day 32 in rats dosed with isoniazid-pyridoxal combination. Isoniazid is known to interfere with alanine aminotransferase activity by decreasing the availability of this coenzyme. The mechanism of the cefazolin effect has not been elucidated.