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Effects of growth hormone on antipyrine kinetics in children
Insights
Human growth hormone (hGH) increased total body water in children but did not uniformly alter antipyrine drug metabolism. Caution is advised for children with organ dysfunction during hGH therapy.
Area of Science:
- Pharmacokinetics
- Pediatric Endocrinology
- Drug Metabolism
Background:
- Antipyrine serves as a key indicator for evaluating hepatic drug-metabolizing enzyme activity.
- Human growth hormone (hGH) is used therapeutically in children, necessitating an understanding of its systemic effects.
- Investigating drug kinetics during hGH treatment is crucial for safe and effective pediatric care.
Purpose of the Study:
- To examine the pharmacokinetic changes of antipyrine in children undergoing short-term or long-term human growth hormone (hGH) treatment.
- To assess the impact of hGH on antipyrine's volume of distribution (aVd) and serum half-life (t 1/2).
- To evaluate potential alterations in drug metabolism and body water content induced by hGH therapy.
Main Methods:
- Kinetics of antipyrine were analyzed in pediatric subjects before and after short-term (5 days to 1 wk) and long-term (6 wk to 1 yr) hGH treatment.
- Measurements included antipyrine's volume of distribution (aVd) as a proxy for total body water.
- Serum half-life (t 1/2) and metabolic clearance rates of antipyrine were determined to assess drug metabolism.
Main Results:
- Short-term hGH treatment significantly increased the mean antipyrine volume of distribution (aVd) from 0.49 to 0.58 l/kg (p < 0.005).
- The mean aVd was not significantly altered after long-term hGH treatment, though individual increases were observed.
- Neither mean serum half-life (t 1/2) nor metabolic clearance of antipyrine was uniformly affected by hGH, but significant inter-individual variability in t 1/2 changes was noted.
Conclusions:
- Human growth hormone (hGH) can increase total body water in children, warranting cautious use in those with cardiac, renal, or hepatic impairment.
- hGH may variably alter antipyrine's half-life in some children, suggesting potential impacts on drug metabolism.
- The unpredictable nature of these changes necessitates individualized monitoring and potential dosage adjustments for co-administered drugs during hGH therapy.
Abstract:
The kinetics of antipyrine, a drug used as a clinical indicator of hepatic drug-metabolizing enzyme activity, were examined in children after short- (5 days to 1 wk) or long-term (6 wk to 1 yr) treatment with human growth hormone (hGH). After short-term treatment the mean volume of distribution of antipyrine (aVd) (also a measure of total body water) increased from 0.49 to 0.58 l/kg (p less than 0.005). The mean aVd after long-term treatment did not differ from the mean pretreatment value, but it rose in three of the eight subjects examined. Neither the mean serum half-life (t 1/2) nor the metabolic clearance rate of antipyrine for the group as a whole was altered after short- or long-term treatment with hGH. However, t 1/2 rose to 135% to 151% of control value in three of nine children and decreased to 63% of control value in one after short-term treatment, while after long-term treatment it rose to 128% to 176% of control value in four of eight children. The results indicate that hGH can increase total body water and should be used cautiously in children with impaired cardiac, renal, or hepatic function. The data further suggest that hGH may alter antipyrine t 1/2 in some children. The variable nature of the changes precludes any uniform prediction about growth hormone effects on drug metabolism, but it may be necessary in some children to modify the dosage of other drugs administered with hGH.