A Pharmacokinetic Standard for Babies and Adults

doi:10.1002/jps.23574

Journal of Pharmaceutical Sciences

Volume 102, Issue 9, September 2013, Pages 2941-2952

https://doi.org/10.1002/jps.23574 Get rights and content

ABSTRACT:

The pharmacokinetic behavior of medicines used in humans follows largely predictable patterns across the human age range from premature babies to elderly adults. Most of the differences associated with age are in fact due to differences in size. Additional considerations are required to describe the processes of maturation of clearance processes and postnatal changes in body composition. Application of standard approaches to reporting pharmacokinetic parameters is essential for comparative human pharmacokinetic studies from babies to adults. A standardized comparison of pharmacokinetic parameters obtained in children and adults is shown for 46 drugs. Appropriate size scaling shows that children (over 2 years old) are similar to adults. Maturation changes are generally completed within the first 2 years of postnatal life; consequently babies may be considered as immature children, whereas children are just small adults. © 2013 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 102:2941–2952, 2013

Section snippets

BABIES TO ADULTS

Medicines are used throughout the human age span. Arguably, the most critical decisions about the use of medicines, particularly those related to dose, are made in very premature infants. Medicines in that age group may be essential for life and treatment consequences, both beneficial and adverse, will literally be life-long. At the other end of the age spectrum the elderly adult is also a frequent consumer of medicines for a wide range of diseases.

Rational dosing of medicines is based on the

WHAT IS PHARMACOKINETICS ABOUT?

Pharmacokinetics is primarily concerned with the time course of drug concentration in the body. Sometimes only the steady state concentration is of interest and then time is no longer of relevance. The time course of concentration is determined by three processes: input, distribution, and elimination. These processes are more general than the traditional “absorption, distribution, metabolism, excretion” description because input processes are more than just absorption and elimination covers

A STANDARD APPROACH

Benet is justifiably renowned for his wide ranging studies of pharmacokinetics. He is also known for originating an extensive table of the pharmacokinetic properties of drugs.⁹⁶ He has recommended that theory based allometry be used to scale clearances for body size but apart from some qualitative hints there is no guidance on how to account for maturation in neonates, infants or children. We note, with some dismay, that later editions of this table, for example,²⁶ have reverted to less

CONCLUSION

Comparison of parameter estimates across studies is facilitated by using a common standard.⁸ We strongly encourage scientists studying pharmacokinetics in children and adults to report values using a standard weight of 70 kg scaled using theory based allometry. We also encourage the use of maturation functions that extrapolate plausibly to both extremes of the age spectrum such as the sigmoid maturation model. Using a common standard for reporting parameters base on size and maturation models

ACKNOWLEDGMENT

The authors received no specific funding for the preparation of this work apart from their usual salary.

Conflict of interest: No conflicts of interest are identified.

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