title: Diabetes and elimination of antipyrine in man: an analysis of 298 patients classified by type of diabetes, age, sex, duration of disease and liver involvement.
abstract: Effects of diabetes on hepatic drug metabolism in man has not yet been adequately clarified. Two hundred ninety-eight diabetic patients, classified by type of the disease, age, gender, duration of therapy and liver involvement, were investigated. The antipyrine plasma clearance rate and cytochrome P450 content determinations in liver biopsies of subjects with diagnostic liver biopsy were used as indices of hepatic drug metabolising capacity. Drug metabolism was reduced as a function of age. Antipyrine elimination rate was dependent on the type of diabetes (type 1 versus type 2) and gender. Untreated type 1 patients eliminated antipyrine rapidly and insulin treatment normalised antipyrine elimination (clearance rates 89.5 +/- 20.3 versus 58.8 +/- 17.2 ml/min.; P<0.001). Males aged 16-59 years, but not over 60, who responded insufficiently to insulin therapy, had a rapid antipyrine elimination, which could be normalised by readjustment of insulin administration. Women with insufficient glucose control on insulin therapy had antipyrine elimination rate comparable to controls. Among type 2 diabetic patients, women metabolised antipyrine normally, but men over 40 years of age showed a reduced antipyrine metabolism.
  
  
  CONCLUSIONS
  Drug metabolism in diabetes is affected by the type of disease, therapy and its effectiveness, and age and gender of the patients. These factors should be taken into account when evaluating overall drug metabolism in diabetic patients. This is especially important when investigating pharmacokinetics of new drugs for diabetic patients at different phases of the disease.
authors.affiliation: Department of Internal Medicine, University of Oulu, Finland.
authors.forename: Eero A
authors.initials: EA
authors.lastname: Sotaniemi
authors.forename: Olavi
authors.initials: O
authors.lastname: Pelkonen
authors.forename: Arno J
authors.initials: AJ
authors.lastname: Arranto
authors.forename: Päivi
authors.initials: P
authors.lastname: Tapanainen
authors.forename: Arja
authors.initials: A
authors.lastname: Rautio
authors.forename: Markku
authors.initials: M
authors.lastname: Pasanen
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000493:pharmacokinetics*; D000983:Antipyrine / Q000493:pharmacokinetics* / Q000652:urine; D001786:Blood Glucose / Q000032:analysis / Q000187:drug effects; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D005260:Female; D006801:Humans; D007328:Insulin / Q000008:administration & dosage; D008099:Liver / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D012737:Sex Factors; D013997:Time Factors
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D001786:Blood Glucose; D007328:Insulin; D003577:Cytochrome P-450 Enzyme System; D000983:Antipyrine