Abstract
Animal experiments have documented alterations in hepatic drug metabolism in diabetic rats. In addition to abnormalities in glycosylation of hemoglobin other heme proteins such as cytochrome P-450 might also be expected to be altered. We report here changes in cytochrome P-450 dependent drug metabolizing activity in children with IDDM. We have studied antipyrine (AP) kinetics in 8 children (age 10-22 yr) with IDDM of at least 3 months duration who were all in poor control as defined by Hgb Al levels. Liver function tests and renal function were normal. Insulin dose ranged between 0.5-1 U/kg. AP (test dose 16 mg/kg p.o.) is widely used as a measure of hepatic drug metabolism in man. Its elimination from plasma is largely determined by hepatic oxidizing enzyme activity. AP kinetics were compared to age matched controls (mean±l SD) AVD: volume of distribution.
In three IDDM patients with near nl Hgb Al levels (6.8,7.1,8%) AP t½ was nl when compared to age matched controls (8.1,9.2,8hr) as was AP clearance.
Conclusion: In poorly controlled IDDM hepatic drug metabolism may be altered: AP clearance is increased, AP t½ is shortened. In well controlled IDDM antipyrine drug metabolism appears to be nl. These findings provide another cogent argument for tight metabolic control in youngsters with IDDM.
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Saenqer, P. 144 ALTERED DRUG METABOLISM IN POORLY CONTROLLED INSULIN DEPENDENT DIABETES MELLITUS (IDDM). Pediatr Res 19, 627 (1985). https://doi.org/10.1203/00006450-198506000-00164
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DOI: https://doi.org/10.1203/00006450-198506000-00164