Prediction of drug clearance in children from adults: a comparison of several allometric methods.
OBJECTIVE
In recent years with the advent of paediatric exclusivity and requirements to conduct clinical studies in children, the current emphasis is to find a safe and efficacious dose of a drug in children. It has been suggested that one can predict the clearance of a drug in children according to the equation: CL in the child=adult CLx(weight of the child/70)0.75. Considering the controversy surrounding the exponent of 0.75 for the prediction of clearance and lack of any systematic evaluation of the aforementioned proposal, the objectives of the study were as follows: (i) to determine if indeed the exponent 0.75 is the most suitable exponent for the prediction of clearance in children from adult data; (ii) to explore and search for other exponents that are more accurate or as good as 0.75; and (iii) to propose a new approach (if any) based on the findings of the current evaluation.


METHODS
Six methods were used to predict clearance of drugs in children from adult data. Besides evaluating the exponent of 0.75, exponents of 0.80, 0.85 and 1.0 were also evaluated. An empirical approach based on kidney and liver weights was also examined. Based on the results of five methods, a sixth method was introduced.


RESULTS
The results of the study indicate that no single method is suitable for all drugs or for all age groups. The exponents 0.75, 0.80, and 0.85 provided the same degree of accuracy or error in the prediction of clearance in children.


CONCLUSIONS
Since no single method is suitable for all drugs or for all age groups. A combination of approaches is suggested which may help in improving the prediction of clearance in children from adult data.
Mahmood
Iftekhar
I
Clinical Pharmacology and Toxicology Branch, Office of Drug Evaluation VI, Center for Drug Evaluation and Research, Food & Drug Administration, Rockville, MD 20852, USA. mahmoodi@cder.fda.gov