Drug metabolism, pharmacokinetic pediatric patients

Valproic acid is eliminated by first-order kinetics and has an elimination half-life of 5-20 hours (average, 10.6 hours). Pediatric patients (3 months to 10 years) have a 50% higher clearance of the drug expressed by weight (i.e., mL/min/kg) over the age of 10 years, pharmacokinetic parameters of valproic acid approximate those in adults (Cloyd et al., 1993). Valproic acid is metabolized principally in the liver by (3 (over 40%) and CO oxidation (up to 15%-20%). Thirty through 50% of an administered dose is excreted as glucuron-ide conjugates (Cloyd et al., 1993). 

The in silico prediction of pharmacokinetic behavior in pediatric patients indicated the complexity of age related changes such that the clearance of drugs metabolized by the same enzymes took different patterns (Fig. 16.6), possibly due to other elements of PK such as differences in protein binding, red blood cell distribution, etc. 

Enormous progress has been made in pharmacokinetics in pediatric patients. Two factors have contributed to this progress (1) the availability of sensitive and specific analytic methods to measure drugs and their metabohtes in small volumes of biologic fluids and (2) awareness of the importance of chnical pharmacokinetics in optimization of drug therapy. Absorption, distribution, metabolism, and elimination of many drugs are different in premature infants, fuU-term infants, and older children, and this topic is discussed in detail in the next few sections. 

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