Adolescent dosing and labeling since the Food and Drug Administration Amendments Act of 2007.
OBJECTIVE
During pediatric drug development, dedicated pharmacokinetic studies are generally performed in all relevant age groups to support dose selection for subsequent efficacy trials. To our knowledge, no previous assessments regarding the need for an intensive pharmacokinetic study in adolescents have been performed.


OBJECTIVE
To compare U.S. Food and Drug Administration (FDA)-approved adult and adolescent drug dosing and to assess the utility of allometric scaling for the prediction of drug clearance in the adolescent population.


METHODS
Adult and adolescent dosing and drug clearance data were obtained from FDA-approved drug labels and publicly available databases containing reviews of pediatric trials submitted to the FDA. Dosing information was compared for products with concordant indications for adolescent and adult patients. Adolescent drug clearance was predicted from adult pharmacokinetic data by using allometric scaling and compared with observed values.


METHODS
Adolescent and adult dosing information and drug clearance.


RESULTS
There were 126 unique products with pediatric studies submitted to the FDA since the FDA Amendments Act of 2007, of which 92 had at least 1 adolescent indication concordant with an adult indication. Of these 92 products, 87 (94.5%) have equivalent dosing for adults and adolescent patients. For 18 of these 92 products, a minimum weight or body surface area threshold is recommended for adolescents to receive adult dosing. Allometric scaling predicted adolescent drug clearance with an overall mean absolute percentage error of 17.0%.


CONCLUSIONS
Approved adult and adolescent drug dosing is equivalent for 94.5% of products with an adolescent indication studied since the FDA Amendments Act of 2007. Allometric scaling may be a useful tool to avoid unnecessary dedicated pharmacokinetic studies in the adolescent population during pediatric drug development, although each development program in adolescents requires a full discussion of drug dosing with the FDA.
Office of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, Maryland.
Jeremiah D
JD
Momper
Yeruk
Y
Mulugeta
Dionna J
DJ
Green
Alyson
A
Karesh
Kevin M
KM
Krudys
Hari C
HC
Sachs
Lynn P
LP
Yao
Gilbert J
GJ
Burckart
D000293:Adolescent; D000328:Adult; D001835:Body Weight; D017277:Drug Approval / Q000331:legislation & jurisprudence*; D004348:Drug Labeling / Q000331:legislation & jurisprudence* / Q000706:statistics & numerical data; D005260:Female; D006801:Humans; D008297:Male; D008657:Metabolic Clearance Rate; D008954:Models, Biological; D004364:Pharmaceutical Preparations / Q000008:administration & dosage*; D010599:Pharmacokinetics; D014481:United States; D014486:United States Food and Drug Administration
D004364:Pharmaceutical Preparations