Young's Rule

Christian Wade; Thirsa Martinez

Young's Rule

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Definition/Introduction

Young's Rule is an equation used to calculate pediatric medication dosage based on patient age and the known recommended adult dose. The definition of Young's Rule is the age of the patient divided by the age added to twelve, all multiplied by the recommended adult dose. This formula appears below:

[Age / (Age + 12)] x Recommended Adult Dose = Pediatric Dose

Young's Rule can be applied quickly in situations where the current weight of the patient is unknown. Other approaches to pediatric dosing using age include the Webster and Fried rules.[1]

The Clark Rule or the Body Surface Area Rule can be implemented if the weight of the patient is known.[2]

Issues of Concern

Pediatric dosing based on age has the potential for suboptimal therapeutic levels due to the broad range of potential weight, especially with increasing childhood obesity. Young's Rule cannot be used for newborns, and consideration must be given to growth variability at the given age.[3][4] Physiologically Based Pharmacokinetic (PBPK) models have been developed, which can direct drug dose selection in pediatric patients.[5] The Food and Drug Administration (FDA) endorses using PBPK modeling on a case-by-case basis.[6] However, these models rely on simulation and are more useful for the drug development process rather than routine clinical practice.[6]

It should be noted that Young's Rule can be a guide for dosing but is not accurate for pediatric dose prediction. The activity of cytochrome P450 enzymes depends on age, leading to high inter- and intra-individual variability in the pediatric population.[7] Consequently, therapeutic drug monitoring(TDM) should be considered for drugs with a narrow therapeutic index.[8]

Clinical Significance

In situations where the weight of the pediatric patient is unknown, for instance, at the point of injury, Young's Rule can be safely implemented if the patient age and the recommended adult dosing are known. Age and the disease state can change the pharmacodynamics and pharmacokinetics of the drug; consequently, an adjustment in the dosing regimen in children is necessary.[9] Additionally, certain medications require weight-based dosings, such as antibiotics and antiepileptics. Ultimately, age-based dosing has been demonstrated to be a safe and effective approach. However, caution should be used depending on the class of the drug. Young's Rule can be valuable when there is limited information about pediatric dosing in the product labeling provided by the manufacturer.[10][11]

Nursing, Allied Health, and Interprofessional Team Interventions

Knowledge of Young's Rule can serve several purposes in pediatric drug dosing, and interprofessional healthcare team members should be familiar with it. The most obvious use is for the clinician when calculating the dose for a pediatric patient. A secondary use can be to verify that the dose ordered or prescribed is not outside of the parameters for the child. This is where nurses, during administration or pharmacists, when filling an order or prescription, can apply the Young's Rule and potentially prevent a toxic or therapeutically insufficient dose from being dispensed. In an open, interprofessional team environment, this can improve patient outcomes and prevent adverse events. [Level V]

Details

References

[1]

Mahmood I. A comparison of different methods for the first-in-pediatric dose selection. Journal of clinical and translational research. 2022 Oct 31:8(5):369-381 [PubMed PMID: 36518546]

[2]

Delgado BJ, Safadi AO, Bajaj T. Clark's Rule. StatPearls. 2023 Jan:(): [PubMed PMID: 31082148]

[3]

Ogden CL, Carroll MD, Lawman HG, Fryar CD, Kruszon-Moran D, Kit BK, Flegal KM. Trends in Obesity Prevalence Among Children and Adolescents in the United States, 1988-1994 Through 2013-2014. JAMA. 2016 Jun 7:315(21):2292-9. doi: 10.1001/jama.2016.6361. Epub [PubMed PMID: 27272581]

[4]

Kendrick JG, Carr RR, Ensom MH. Pharmacokinetics and drug dosing in obese children. The journal of pediatric pharmacology and therapeutics : JPPT : the official journal of PPAG. 2010 Apr:15(2):94-109 [PubMed PMID: 22477800]

[5]

Wang K, Jiang K, Wei X, Li Y, Wang T, Song Y. Physiologically Based Pharmacokinetic Models Are Effective Support for Pediatric Drug Development. AAPS PharmSciTech. 2021 Jul 26:22(6):208. doi: 10.1208/s12249-021-02076-w. Epub 2021 Jul 26 [PubMed PMID: 34312742]

[6]

Jean D, Naik K, Milligan L, Hall S, Mei Huang S, Isoherranen N, Kuemmel C, Seo P, Tegenge MA, Wang Y, Yang Y, Zhang X, Zhao L, Zhao P, Benjamin J, Bergman K, Grillo J, Madabushi R, Wu F, Zhu H, Zineh I. Development of best practices in physiologically based pharmacokinetic modeling to support clinical pharmacology regulatory decision-making-A workshop summary. CPT: pharmacometrics & systems pharmacology. 2021 Nov:10(11):1271-1275. doi: 10.1002/psp4.12706. Epub 2021 Sep 18 [PubMed PMID: 34536337]

[7]

Magliocco G, Rodieux F, Desmeules J, Samer CF, Daali Y. Toward precision medicine in pediatric population using cytochrome P450 phenotyping approaches and physiologically based pharmacokinetic modeling. Pediatric research. 2020 Feb:87(3):441-449. doi: 10.1038/s41390-019-0609-z. Epub 2019 Oct 10 [PubMed PMID: 31600772]

[8]

Simeoli R, Dorlo TPC, Hanff LM, Huitema ADR, Dreesen E. Editorial: Therapeutic Drug Monitoring (TDM): A Useful Tool for Pediatric Pharmacology Applied to Routine Clinical Practice. Frontiers in pharmacology. 2022:13():931843. doi: 10.3389/fphar.2022.931843. Epub 2022 May 24 [PubMed PMID: 35685621]

Level 3 (low-level) evidence

[9]

Mahmood I. Dosing in children: a critical review of the pharmacokinetic allometric scaling and modelling approaches in paediatric drug development and clinical settings. Clinical pharmacokinetics. 2014 Apr:53(4):327-46. doi: 10.1007/s40262-014-0134-5. Epub [PubMed PMID: 24515100]

[10]

Elias GP, Antoniali C, Mariano RC. Comparative study of rules employed for calculation of pediatric drug dosage. Journal of applied oral science : revista FOB. 2005 Jun:13(2):114-9 [PubMed PMID: 20924533]

Level 2 (mid-level) evidence

[11]

Kendrick JG, Carr RR, Ensom MH. Pediatric Obesity: Pharmacokinetics and Implications for Drug Dosing. Clinical therapeutics. 2015 Sep 1:37(9):1897-923. doi: 10.1016/j.clinthera.2015.05.495. Epub [PubMed PMID: 26361823]