Antiepileptic drugs, hepatic enzyme induction and raised serum alkaline phosphatase isoenzymes.

Thirteen patients with epilepsy on long-term antiepileptic drug therapy and who had a persistently raised serum alkaline phosphatase (ALP) activity were investigated biochemically. Twelve patients had a raised liver ALP-isoenzyme activity and in nine of these the bone ALP-isoenzyme activity was normal. Gamma-glutamyl transferase (gamma GT) levels were raised in 12 patients. Two patients were hypoglycaemic. One patient fitted the biochemical parameters for subclinical osteomalacia. The resultant clinical picture showed 75% of patients with borderline hypocalcaemia, raised liver ALP, raised gamma GT and normal bone ALP activities in whom 1,25 dihydroxy-cholecalciferol (1,25-DHCC; vitamin D) therapy would be inappropriate, whilst 1,25-DHCC therapy might be considered for those with borderline hypocalcaemia and a raised bone ALP activity (three patients). No evidence was found of hepatotoxicity or drug induced cholestasis. It is considered that the induction of liver microsomal enzymes by antiepileptic drugs could include liver ALP (as opposed to bone ALP) as well as gamma GT and the inactivation pathways for 1,25 DHCC.