Hepatic drug metabolism is increased in poorly controlled insulin-dependent diabetes mellitus.
In addition to increased glycosylation of hemoglobin, abnormalities of other heme proteins such as cytochrome P-450 might also occur in patients with insulin-dependent diabetes mellitus. Antipyrine is a useful marker drug for cytochrome P-450 dependent hepatic drug metabolism. Antipyrine kinetics and urinary excretion of antipyrine metabolites were measured in 14 patients with insulin-dependent diabetes mellitus in poor metabolic control. Improvement in diabetic control in 9 patients, as measured by more normal HbA1 values, led to normalization of plasma antipyrine half-time (t1/2) and metabolism: the mean antipyrine t1/2 slowed from 4.7 +/- 0.2 (SEM) initially to 7.8 +/- 0.3 h in these 9 patients and was thus nearly identical to that of normal subjects 8.6 +/- 1.0. Antipyrine plasma clearance improved in the 9 diabetic patients whose diabetic control improved. The apparent volume of distribution was normal on both occasions in the diabetic patients. These findings provide a new argument for tight metabolic control in patients with insulin-dependent diabetes mellitus.
Goldstein
S
S
Department of Pediatrics, Montefiore Medical Center/Albert Einstein College of Medicine, Bronx, New York.
Simpson
A
A
Saenger
P
P
D000293:Adolescent; D000328:Adult; D000983:Antipyrine / Q000493:pharmacokinetics*; D002648:Child; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism*; D005260:Female; D005500:Follow-Up Studies; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D007328:Insulin / Q000627:therapeutic use; D008099:Liver / Q000378:metabolism*; D008297:Male
D000983:Antipyrine; D006442:Glycated Hemoglobin; D007328:Insulin