Pediatric Principles 1 2024 PDF

PHM101: PHARMACOTHERAPY MODULE I PEDIATRIC PRINCIPLES: I Pharmacokinetic Considerations Charisse De Castro, RPh, BScPhm, PharmD, ACPR Clinical Pharmacist, The Hospital for Sick Children Wednesday, February 7, 2024  Pediatric Principles: Series I-III Basics & Pediatric...

PHM101: PHARMACOTHERAPY MODULE I PEDIATRIC PRINCIPLES: I Pharmacokinetic Considerations Charisse De Castro, RPh, BScPhm, PharmD, ACPR Clinical Pharmacist, The Hospital for Sick Children Wednesday, February 7, 2024  Pediatric Principles: Series I-III Basics & Pediatric Talking to Development Pharmacotherapy Families Pharmacokinetic/ Dosing & Medication history, Pharmacodynamic Dosage Forms Vaccines, Counselling 2  OBJECTIVES By the end of this presentation, you should be able to: 1. Define neonate, infant, child and adolescent 2. Contrast the differences in pharmacokinetics (i.e. absorption, distribution, metabolism, elimination) between children and adults 3. Describe the role of therapeutic drug monitoring (TDM) in pediatrics  Patient Case 8 day old boy (4 kg) comes into the Emergency Department with fever and lethargy > suspected sepsis Team wants to start antibiotics: ampicillin and tobramycin MD asks what dose of tobramycin he should order MD is an adult resident doing a pediatric rotation at SickKids He remembers that the adult dose is 1mg/kg IV q8h For example, for a 70 kg adult patient, dose = 70 mg IV q8h He asks if he can use the same weight-based dosing for this baby For example, for our 4 kg neonatal patient, dose = 4 mg IV q8h Is this dose correct? What other information do you need? “Children are not little adults” DEFINITIONS Pediatrics: Age Definitions for Dosing Age Category 0 – 1 month Neonate 1 month – 1 year Infant 1 year – 11 years Child* 12 – 18 years Adolescent *Child can be further categorized as: Toddler (>12 months – 23 months) Preschool child (2-5 years) School age child (6-11 years)  Neonates: Premature vs Term Premature Full Term Gestational age < 37 weeks at birth Gestational age 37-42 weeks at birth  PMA = GA + PNA Used with permission from Jennifer Chen  Why do these definitions matter? Dosing in pediatrics can be by: – Weight – Age – Prematurity (e.g. post-menstrual age) – Body surface area – A combination of the above Dosing Example  Back to our case… 8 day old boy (4 kg) comes into the Emergency Department with fever and lethargy > suspected sepsis Team wants to start antibiotics: ampicillin and tobramycin MD asks what dose of tobramycin he should order MD is an adult resident doing a pediatric rotation at SickKids He remembers that the adult dose is 1mg/kg IV q8h For example, for a 70 kg adult patient, dose = 70 mg IV q8h He asks if he can use the same weight-based dosing for this baby For example, for our 4 kg neonatal patient, dose = 4 mg IV q8h Is this dose correct? What other information do you need? Post-menstrual age (PMA)  DEVELOPMENT & DRUG DISPOSITION  PHARMACOKINETICS Time course of drug absorption, distribution, metabolism and elimination  ABSORPTION Movement of drug from site of administration to bloodstream  Bioavailability of enteral drugs Adults Neonates Intragastric pH = 2 Intragastric pH > 4 Due to lower acid production Greater bioavailability of acid-labile drugs such as penicillin Protected in an environment with higher pH Reduced bioavailability of weakly acidic drugs such as phenobarbital and phenytoin Due to increased ionization in a high-pH environment → decreased lipid solubility Rate and extent of enteral absorption Adults Neonates Normal gastric emptying Delayed gastric emptying/reduced GI motility Reduced intestinal absorption surface area Shorter gut transit time Delayed absorption of drugs such as phenobarbital, digoxin and sulfonamides  Extent of skin absorption Adults Neonates & Infants Normal skin absorption Thinner stratum corneum Greater cutaneous perfusion & epidermal hydration Increased systemic absorption of topical drugs → can result in systemic toxicity Examples: Potent topical steroids such as clobetasol and betamethasone ointment can cause adrenal suppression Topical lidocaine can cause seizures Topical povidone iodine (antiseptic) can cause hypothyroxinemia  DISTRIBUTION Movement of drugs through various body organs, tissues, fluids  Volume of Distribution (Vd) Adults Neonates, Infants & Children Total body water ~60% Neonates have higher total body water (~80-85%) Example: Gentamicin (hydrophilic) Example: Gentamicin (hydrophilic) Vd = 0.2-0.3 L/kg Vd = 0.45 L/kg for neonates (larger) Vd = 0.4 L/kg for infants Vd = 0.35 L/kg for children Vd = 0.3 L/kg for adolescents For hydrophilic drugs (e.g. tobramycin): If the same weight-based dose was given, neonates would have a lower drug concentration than adults Neonates need a higher dose to achieve similar peaks due to the higher Vd  Volume of Distribution (Vd) Adults Neonates Fat content ~13% Neonates have lower body fat content ( suspected sepsis Team wants to start antibiotics: ampicillin and tobramycin MD asks what dose of tobramycin he should order MD is an adult resident doing a pediatric rotation at SickKids He remembers that the adult dose is 1mg/kg IV q8h For example, for a 70 kg adult patient, dose = 70 mg IV q8h He asks if he can use the same weight-based dosing for this baby For example, for our 4 kg neonatal patient, dose = 4 mg IV q8h Is this dose correct? What other information do you need?  Back to our case… Is this dose correct? No What would you recommend to the MD? How and why is this different from adult dosing? Is there a role for TDM? PEDIATRIC DRUG INFORMATION SOURCES  Pediatric & Neonatal Dosage Handbook Used with permission from Jennifer Chen  Patient & Caregiver Education Used with permission from Jennifer Chen  SickKids Compounding Recipes Used with permission from Jennifer Chen  Take Home Messages “Children are not little adults” Drug dosing in pediatrics is complex and needs to account for drug disposition changes with age (i.e. changes in body composition and organ function) – There are different pharmacokinetic considerations for neonates, infants, children and adolescents Therapeutic drug monitoring is a helpful tool to individualize dosing in pediatrics  Selected References Lim SY, Pettit RS. Pharmacokinetic considerations in pediatric pharmacotherapy. Am J Health Syst Pharm. 2019 Sep 16;76(19):1472-1480. Hoshitsuki K, Fernandez CA, Yang JJ. Pharmacogenomics for Drug Dosing in Children: Current Use, Knowledge, and Gaps. J Clin Pharmacol. 2021 Jun;61 Suppl 1(Suppl 1):S188-S192. Bartelink IH, Rademaker CM, Schobben AF et al. Guidelines on paediatric dosing on the basis ofdevelopmental physiology and pharmacokinetic considerations. Clin Pharmacokinet. 2006; 45(11): 1077-1097. THANK YOU 51