Effects of growth hormone on antipyrine kinetics in children
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.