The effect of bezafibrate treatment on serum alkaline phosphatase isoenzyme activities

Abstract

A reduction in serum total alkaline phosphatase (ALP) activity is a well-documented side effect of treatment with bezafibrate and other fibric acid derivatives. To evaluate the effect of bezafibrate treatment on individual ALP isoenzyme activities, 10 patients were studied on two separate occasions, first, after a 6-week period on no drug treatment, and second, after 6 weeks of bezafibrate therapy. On each occasion, serum total ALP and ALP isoenzyme activities and serum γ-glutamyltransferase (GGT) activity were measured both after fasting and following the ingestion of a standardized high-fat meal rich in long-chain fatty acid triglycerides, as intestinal ALP activity is known to be influenced by dietary fat intake. Plasma aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities were measured on fasting samples. In the fasting state, bezafibrate treatment resulted in a 25% reduction ( P < .01) in serum total ALP activity; liver ALP activity was reduced by 40% ( P < .01), and biliary ALP activity was reduced in those patients in whom it was initially detectable, while bone and intestinal ALP activities were unchanged. There was also a 15% reduction ( P < .05) in serum GGT activity, but no change in plasma AST or ALT activities. Serum intestinal ALP activity increased significantly ( P < .01) by 1 hour following ingestion of the high-fat meal, but treatment with bezafibrate did not change the magnitude of this response. There was no change in the activity of any other ALP isoenzyme following fat ingestion. This study demonstrates that the effect of bezafibrate on serum ALP activity is confined to the liver and biliary isoenzymes. Bezafibrate treatment also reduces serum GGT activity, which, like liver and biliary ALP activity, is increased during hepatic cholestasis. The pattern of enzyme changes observed provides information about a possible mechanism for the effect of bezafibrate and other fibric acid derivatives on serum ALP activity.