Evaluation of the influence of diabetes mellitus on antipyrine metabolism and CYP1A2 and CYP2D6 activity

Pharmacotherapy. 2000 Feb;20(2):182-90. doi: 10.1592/phco.


Study objective: To evaluate the metabolism of antipyrine, a general metabolic probe, caffeine, a probe for cytochrome P450 (CYP) 1A2 and N-acetyltransferase activity, and dextromethorphan, a specific probe for CYP2D6 activity in patients with type 1 or 2 diabetes mellitus.

Design: Prospective, controlled study.

Setting: Research facility. Patients. Fifteen patients with type 1 and 16 with type 2 diabetes, and 16 healthy controls.

Intervention: Each subject simultaneously received antipyrine 10 mg/kg, caffeine 100 mg, and dextromethorphan 30 mg.

Measurements and main results: The pharmacokinetics of antipyrine and its primary metabolites were determined from saliva and urine samples. Type 1 diabetes had marked effects on antipyrine metabolism whereas type 2 disease did not alter the metabolism of any of the probe drugs. The apparent oral clearance of antipyrine was increased 72% in patients with type 1 disease compared with controls (p=0.0001). In addition, formation clearances of 4-hydroxyantipyrine and 3-hydroxymethylantipyrine were increased by 74% and 137% in those patients relative to controls. The caffeine metabolic index (paraxanthine/caffeine) was increased 34% (p=0.11), and N-acetylation and CYP2D6 phenotype were not altered.

Conclusion: The metabolism of antipyrine is increased in patients with type 1 diabetes. Based on in vitro reports of antipyrine metabolism and current caffeine metabolic index data, the predominant effect of type 1 diabetes appears to be an increase in CYP1A2 activity. Assessment of the effect of the disease on other specific CYP metabolic pathways is warranted.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylation
  • Adult
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacokinetics*
  • Anti-Inflammatory Agents, Non-Steroidal / urine
  • Antipyrine / pharmacokinetics*
  • Antipyrine / urine
  • Antitussive Agents / pharmacokinetics
  • Antitussive Agents / urine
  • Caffeine / pharmacokinetics
  • Caffeine / urine
  • Central Nervous System Stimulants / pharmacokinetics
  • Central Nervous System Stimulants / urine
  • Cytochrome P-450 CYP1A2 / metabolism*
  • Cytochrome P-450 CYP2D6 / metabolism*
  • Dextromethorphan / pharmacokinetics
  • Dextromethorphan / urine
  • Diabetes Mellitus, Type 2 / metabolism*
  • Diabetes Mellitus, Type 2 / urine
  • Female
  • Half-Life
  • Humans
  • Liver / enzymology
  • Liver / metabolism
  • Male
  • Middle Aged
  • Phenotype
  • Prospective Studies


  • Anti-Inflammatory Agents, Non-Steroidal
  • Antitussive Agents
  • Central Nervous System Stimulants
  • Caffeine
  • Dextromethorphan
  • Cytochrome P-450 CYP1A2
  • Cytochrome P-450 CYP2D6
  • Antipyrine