Induction of cytochromes P-450 in pancreatic disease: consequence, coincidence or cause?
We have examined the pharmacokinetics of antipyrine and of theophylline--validated probes for cytochromes P-450 activities--in a series of patients with pancreatic disease. The half-life of each drug was significantly lower, and its clearance faster, in patients than in controls and this pattern was detected in the subgroups with acute pancreatitis (6), chronic pancreatitis (22), or pancreatic cancer (4). These data suggest induction of cytochromes P-450 in all forms of exocrine pancreatic disease. Enzyme induction is unlikely to be secondary to pancreatic malfunction since there was no correlation between prevailing exocrine status, as assessed by secretin-pancreozymin tests, and the half-life or clearance of either drug. The corollary is that induction of the mono-oxygenases by environmental agents, both recognised and unidentified, is a primary event in pancreatic disease. The possible relevance of this finding is discussed.
D000293:Adolescent; D000328:Adult; D000983:Antipyrine / Q000097:blood; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis*; D004790:Enzyme Induction; D005260:Female; D006207:Half-Life; D006801:Humans; D007700:Kinetics; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000201:enzymology*; D010195:Pancreatitis / Q000201:enzymology*; D013806:Theophylline / Q000097:blood
D003577:Cytochrome P-450 Enzyme System; D013806:Theophylline; D000983:Antipyrine