Neonates drug clearance

As emphasized in Chapter 23, neonates are especially vulnerable to ADRs because they are sometimes exposed to drugs before birth and have immature renal and hepatic drug clearance capacities. Additionally, there is insufficient information on the clinical pharmacology of various drugs in this age group to guide rational pharmacotherapy (38, 39). 

The renal excretion of drugs depends on glomerular filtration, tubular secretion, and tubular absorption. A twofold increase in glomerular filtration occurs in the first 14 days of life [36], The glomerular filtration rate continues to increase rapidly in the neonatal period and reaches a rate of about 86 mL/min per 1.73 m2 by 3 months of age. Children 3-13 years of age have an average clearance of 134 mL/min per 1.73 m2 [37]. Tubular secretion approaches adult values between 2 and 6 months [11], There is more variability observed in maturation of tubular reabsorption capacity. This is likely linked to fluctuations in urinary pH in the neonatal period [38],... 

The plasma clearance of theophylline varies widely. Theophylline is metabolized by the liver, so typical doses may lead to toxic concentrations of the drug in patients with liver disease. Conversely, clearance may be increased through the induction of hepatic enzymes by cigarette smoking or by changes in diet. In normal adults, the mean plasma clearance is 0.69 mL/kg/min. Children clear theophylline faster than adults (1-1.5 mL/kg/min). Neonates and young infants have the slowest clearance (see Chapter 59). Even when maintenance doses are altered to correct for the above factors, plasma concentrations vary widely. 

Johnson, T.N. et al. Prediction of the clearance of eleven drugs and associated variability in neonates, infants and children. Clin Pharmacokinet 2006,45 931-956. 

The influence of the active metabolites becomes more significant with repeated administration of the parent drug, as might occur for the control of seizures (see Ch. 9), or chronic oral administration for continued sedation of a neonatal foal. Foals less than 21 days of age have a lower total body clearance of diazepam than older foals and adult horses and, therefore, a greater tendency to develop effects caused by drug accumulation (Norman et al 1997). 

Because disposition refers to the simultaneous effects of distribution and elimination, it is necessary to consider both components of the process when interpreting changes that occur during the neonatal period. Comparison of the disposition kinetics of enrofloxacin (2.5 mg/kg administered intravenously) in 1-day-old and 1-week-old calves shows that the volume of distribution (Vd(ss)) is smaller and the systemic clearance (C/I5) of the drug is lower in the 1-day-old calves, while the half-life does not differ significantly between the age groups... 

---