Farmacocinética de medicamentos en pacientes pediátricos. Una revisión sistemática
DOI:
https://doi.org/10.26820/recimundo/9.(2).abril.2025.733-749Keywords:
Farmacocinética pediátrica, Dosificación de medicamentos, Ontogenia enzimática, Variabilidad farmacológica, Revisión sistemática PRISMAAbstract
Antecedentes: La farmacocinética (FC) en niños muestra variaciones notables debido a su desarrollo, lo que complica la aplicación de datos obtenidos de adultos. Estas diferencias impactan la seguridad y efectividad de los medicamentos, subrayando la necesidad de contar con evidencia específica para cada grupo de edad. Objetivo: Resumir los parámetros farmacocinéticos (como clearance, vida media y volumen de distribución) en niños, así como sus variaciones en función de la edad, el peso y el desarrollo orgánico. Materiales y Métodos: Se llevó a cabo una revisión sistemática siguiendo la metodología PRISMA. Se realizó una búsqueda en PubMed, Embase y Cochrane (2001-2025) utilizando términos MESH: "pharmacokinetics", "pediatrics", "drug metabolism". Se incluyeron ensayos clínicos y estudios de cohorte que reportaran parámetros de FC en menores de 18 años. Dos revisores evaluaron la elegibilidad, extrajeron datos y analizaron el riesgo de sesgo utilizando herramientas GRADE. Resultados: De 1.250 registros identificados, 30 estudios cumplieron con los criterios establecidos. Se encontraron diferencias significativas en el clearance de fármacos metabolizados por CYP3A4 (por ejemplo, midazolam) entre lactantes y adolescentes (una reducción del 30-50%). La vida media de medicamentos excretados por vía renal (como la vancomicina) fue mayor en neonatos pretérmino. La heterogeneidad fue alta (I² > 75%) en los análisis por subgrupos. Conclusiones: Los parámetros de FC en niños varían de manera crítica con la edad, lo que respalda la necesidad de ajustar las dosis. Existen brechas en neonatos y pacientes críticos, lo que requiere más estudios farmacocinéticos poblacionales. Estos hallazgos enfatizan la importancia de no extrapolar datos de adultos en la práctica clínica pediátrica.Downloads
References
Abdel-Jalil, M., Abdullah, N., Alsous, M., Saleh, M., & Abu-Hammour, K. (2020). A systematic review of population pharmacokinetic analyses of digoxin in the paediatric population. British Journal of Clinical Pharmacology, 86, 1267 - 1280. https://doi.org/10.1111/bcp.14272.
Allegaert, K., & van den Anker, J. N. (2022). Clinical pharmacology in neonates and young infants: The promise of pharmacometrics. Springer.
Anderson, B. J. (2010). Pediatric models for adult target-controlled infusion pumps. Pediatric Anesthesia, 20(3), 223–232. https://doi.org/10.1111/J.1460-9592.2009.03072.X
Bansal, N., Momin, S., Bansal, R., Gurram Venkata, S. K. R., Ruser, L., & Yusuf, K. (2023). Pharmacokinetics of drugs: Newborn perspective. Pediatric Medicine, 7. https://pm.amegroups.org/article/view/7227
Bartelink, I. H., Rademaker, C. M. A., Schobben, A. F. A. M., van den Anker, J. N., van den Anker, J. N., & van den Anker, J. N. (2006). Guidelines on Paediatric Dosing on the Basis of Developmental Physiology and Pharmacokinetic Considerations. Clinical Pharmacokinectics, 45(11), 1077–1097. https://doi.org/10.2165/00003088-200645110-00003
Batchelor, H. K., & Marriott, J. F. (2015). Paediatric pharmacokinetics: key considerations. British journal of clinical pharmacology, 79(3), 395–404. https://doi.org/10.1111/bcp.12267
Cheng, Y., Zhang, Y., Zhang, Y., Liu, M., & Zhao, L. (2024). Population pharmacokinetic analyses of methotrexate in pediatric patients: a systematic review.. European journal of clinical pharmacology. https://doi.org/10.1007/s00228-024-03665-x.
Collins, J. M. (1987). Clinical Pharmacokinetics for the Pediatric Oncologist (pp. 3–13). Springer, Dordrecht. https://doi.org/10.1007/978-94-009-4267-7
Duceppe, M., Kanji, S., Thu, A., Ruo, N., Cavayas, Y., Albert, M., Robert-Halabi, M., Zavalkoff, S., Benichou, L., Samoukovic, G., & Williamson, D. (2023). Pharmacokinetics of Commonly Used Antimicrobials in Critically Ill Pediatric Patients During Extracorporeal Membrane Oxygenation: A Systematic Review. Pediatric Drugs, 25, 515 - 535. https://doi.org/10.1007/s40272-023-00582-x.
Duceppe, M., Kanji, S., Thu, A., Ruo, N., Cavayas, Y., Albert, M., Robert-Halabi, M., Zavalkoff, S., Benichou, L., Samoukovic, G., & Williamson, D. (2023). Pharmacokinetics of Commonly Used Antimicrobials in Critically Ill Pediatric Patients During Extracorporeal Membrane Oxygenation: A Systematic Review. Pediatric Drugs, 25, 515 - 535. https://doi.org/10.1007/s40272-023-00582-x
El-Tahtawy, A., Kokki, H., & Reidenberg, B. E. (2006). Population Pharmacokinetics of Oxycodone in Children 6 Months to 7 Years Old. The Journal of Clinical Pharmacology, 46(4), 433–442. https://doi.org/10.1177/0091270006286433
Gaetani, M., Tomlinson, G., Yasseen, B., Uleryk, E., & Parshuram, C. (2020). 851: precision of pharmacokinetic parameters in children: a systematic review. Critical Care Medicine. https://doi.org/10.1097/01.CCM.0000631544.27139.13.
Gijsen, M., Vlasselaers, D., Spriet, I., & Allegaert, K. (2021). Pharmacokinetics of Antibiotics in Pediatric Intensive Care: Fostering Variability to Attain Precision Medicine. Antibiotics, 10. https://doi.org/10.3390/antibiotics10101182.
Ginsberg, G., Hattis, D., Miller, R., & Sonawane, B. (2004). Pediatric pharmacokinetic data: implications for environmental risk assessment for children. Pediatrics, 113(4 Suppl), 973–983. https://pubmed.ncbi.nlm.nih.gov/15060190/
Gonzalez, D., et al. (2025). Pediatric drug development: Challenges and opportunities. Clinical Pharmacology & Therapeutics, *117*(3), 45-60.
Hattis, D., Ginsberg, G., Sonawane, B., Smolenski, S., Russ, A., Kozlak, M., & Goble, R. (2003). Differences in pharmacokinetics between children and adults--II. Children’s variability in drug elimination half-lives and in some parameters needed for physiologically-based pharmacokinetic modeling. Risk Analysis, 23(1), 117–142. https://doi.org/10.1111/1539-6924.00295
Hoagland, D., Zhao, Y., & Lee, R. E. (2016). Advances in Drug Discovery and Development for Pediatric Tuberculosis. Mini reviews in medicinal chemistry, 16(6), 481–497. https://doi.org/10.2174/1389557515666150722101723
Jovanovi?, M., & Vu?i?evi?, K. (2022). Pediatric pharmacokinetic considerations and implications for drug dosing. Arhiv Za Farmaciju. https://doi.org/10.5937/arhfarm72-37605
Kearns, G. L., et al. (2019). Developmental pharmacology: Ontogeny of drug disposition. Pediatric Research, 85(5), 789-798.
Kong, Y. (2024). Pediatric pharmacokinetics. Archives of Pediatric Critical Care. https://doi.org/10.32990/apcc.2024.00150 https://www.apccjournal.org/m/journal/view.php?number=31
Lim, S. Y., & Pettit, R. S. (2019). Pharmacokinetic considerations in pediatric pharmacotherapy. American Journal of Health-System Pharmacy, 76(19), 1472–1480. https://doi.org/10.1093/AJHP/ZXZ161
Mahmood, I. (2023). Dosing in children: A population-based approach. Journal of Clinical Pharmacology, 63(2), 134-147.
McCann, M. E., Sethna, N. F., Mazoit, J.-X., Sakamoto, M., Rifai, N., Hope, T., Sullivan, L. J., Auble, S. G., & Berde, C. B. (2001). The pharmacokinetics of epidural ropivacaine in infants and young children. Anesthesia & Analgesia, 93(4), 893–897. https://doi.org/10.1097/00000539-200110000-00018
Mohammed, B. S., Cameron, G. A., Helms, P. J., & McLay, J. S. (2014). Pharmacokinetics of Single Dose Intravenous Paracetamol in Children. 3(2), 18–23. https://doi.org/10.4314/JMBS.V3I2.4
Mohammed, B. S., Cameron, G. A., Helms, P. J., & McLay, J. S. (2014). Pharmacokinetics of Single Dose Intravenous Paracetamol in Children. 3(2), 18–23. https://doi.org/10.4314/JMBS.V3I2.4
Momper, J. D., et al. (2021). Neonatal drug safety: Pharmacokinetic challenges. Pediatrics, 147(4), e2020049632.
Mufti, K., Juárez-Hernández, J., Gheshlaghi, N., Lovnicki, J., Rassekh, S., Ross, C., Carleton, B., & Loucks, C. (2024). The Influence of Pharmacogenetic Factors on the Pharmacokinetics of Morphine and Its Metabolites in Pediatric Patients: A Systematic Review.. Anesthesia and analgesia. https://doi.org/10.1213/ANE.0000000000007349.
Potts, A. L., Warman, G. R., & Anderson, B. J. (2008). Dexmedetomidine disposition in children: a population analysis. Pediatric Anesthesia, 18(8), 722–730. https://doi.org/10.1111/J.1460-9592.2008.02653.X
Romero-Maldonado, W. L. ., Mesa-Cano, I. C. ., Ramírez-Coronel, A. A. ., & Moyano-Brito, E. G. . (2021). Medicamentos de alto riesgo en pediatría: Revisión sistemática . Pro Sciences: Revista De Producción, Ciencias E Investigación, 5(40), 212–222. https://doi.org/10.29018/issn.2588-1000vol5iss40.2021pp212-222
Saavedra, S., Quiñones, L., Saavedra, M., Sasso, J., León, J., & Roco, Á. (2008). Farmacocinética de medicamentos de uso pediátrico, visión actual. Revista Chilena de Pediatría, 79(3), 249–258. https://doi.org/10.4067/S0370-41062008000300002
Salem, F., et al. (2024). PBPK modeling in pediatrics: Current status. AAPS Journal, 26(1), 12.
Singh, K., Franson, T., McCune, S., Jorgensen, D., Getz, K., Bearer, C., & Davis, J. M. (2025). Breaking the silence: challenges and opportunities in pediatric drug development. Pediatric research, 10.1038/s41390-025-03923-3. Advance online publication. https://doi.org/10.1038/s41390-025-03923-3
Smits, A., et al. (2022). Age-dependent changes in drug metabolism. British Journal of Clinical Pharmacology, 88(6), 2345-2357.
Spadoni C. (2018). Pediatric Drug Development: Challenges and Opportunities. Current therapeutic research, clinical and experimental, 90, 119–122. https://doi.org/10.1016/j.curtheres.2018.12.001
Stokes, M., Kamel, N., Festa, M., Sandaradura, I., & Stocker, S. (2025). Scoping Review of Paediatric Population Pharmacokinetic Models of Morphine. Clinical Pharmacokinetics, 64, 791 - 813. https://doi.org/10.1007/s40262-025-01477-5.
Sutiman, N., Koh, J., Watt, K., Hornik, C., Murphy, B., Chan, Y., & Lee, J. (2019). Pharmacokinetics Alterations in Critically Ill Pediatric Patients on Extracorporeal Membrane Oxygenation: A Systematic Review. Frontiers in Pediatrics, 8. https://doi.org/10.3389/fped.2020.00260.
Thangaraju, P., Velmurugan, H., & N, K. (2022). Current Status of Pharmacokinetic Research in Children: A Systematic Review of Clinical Trial Records.. Current reviews in clinical and experimental pharmacology. https://doi.org/10.2174/2772432818666221223155455.
van den Anker, J., & Allegaert, K. (2012). Clinical pharmacology in neonates and young infants: the benefit of a population-tailored approach. Expert review of clinical pharmacology, 5(1), 5–8. https://doi.org/10.1586/ecp.11.65
van den Anker, J., et al. (2020). Optimizing drug therapy for children. Nature Reviews Drug Discovery, 19(1), 23-38.
Vilo, S., Rautiainen, P., Kaisti, K. K., Aantaa, R., Scheinin, M., Manner, T., & Olkkola, K. T. (2008). Pharmacokinetics of intravenous dexmedetomidine in children under 11 yr of age. BJA: British Journal of Anaesthesia, 100(5), 697–700. https://doi.org/10.1093/BJA/AEN070
Vu?i?evi?, K. (2022). Pediatric pharmacokinetic considerations and implications for drug dosing. Arhiv Za Farmaciju https://www.researchgate.net/publication/362028431_Pediatric_pharmacokinetic_considerations_and_implications_for_drug_dosing
Wagner, J., & Abdel-Rahman, S. M. (2013). Pediatric pharmacokinetics. Pediatrics in review, 34(6), 258–269. https://doi.org/10.1542/pir.34-6-258
Wagner, J., & Abdel-Rahman, S. M. (2022.). Pediatric Pharmacokinetics. https://doi.org/10.1542/pir.34-6-258
Zhao, W., et al. (2024). Pharmacokinetics of anticancer drugs in children. Cancer Chemotherapy and Pharmacology, 93(4), 321-335.
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2025 Ana de la Mercedes Grijalva Endara, William Johny Jiménez Jiménez, Mara Carolina Triviño Bonilla, María de los Angeles Castillo Castillo
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.
