Pharmacokinetic variability in the adolescent: implications of body size and organ function for dosage regimen design.
Although there are convincing clinical studies demonstrating important pharmacokinetic differences between the adult and pediatric patient, guidelines for adjusting the dosages of specific drugs are often based on empirical and limited data. Adult doses often provide the reference point for therapy in children with adjustment for body size. Both body weight and body surface area (BSA) are commonly used to adjust adult doses for pediatric patients but yield substantially different absolute doses. For the child age five years, the BSA-based dose will be more than 50 percent greater than the dose adjusted for body weight. The choice of weight or BSA is often arbitrary and may be an important confounding variable when evaluating drugs over wide ranges of age in pediatric patients or comparing two drugs for which doses are not adjusted in a similar manner. For example, comparative trials for HIV-infected pediatric patients are evaluating zidovudine dosed by BSA with zalcitabine dosed by body weight. Organ function changes with age in pediatric patients yet little information is available on the effects of maturation on hepatic or renal function and the consequences for drug disposition. The use of model substrates for organ function offers potential for elucidating organ function relative to maturation and, in particular, to those functional capacities associated with the onset of puberty and gender differentiation.
Rodman
J H
JH
Pharmaceutical Department, St. Jude Children's Research Hospital, Memphis, Tennessee 38105.
D000293:Adolescent; D000328:Adult; D000367:Age Factors; D001824:Body Constitution; D001827:Body Height; D001830:Body Surface Area; D001835:Body Weight; D002648:Child; D002675:Child, Preschool; D002986:Clinical Trials as Topic; D005260:Female; D006801:Humans; D007668:Kidney / Q000378:metabolism / Q000502:physiology; D008099:Liver / Q000378:metabolism / Q000502:physiology; D008297:Male; D004364:Pharmaceutical Preparations / Q000008:administration & dosage*; D010599:Pharmacokinetics
D004364:Pharmaceutical Preparations