TABLE 2

Examples Summarizing Changes in Drug Exposure and/or Clearance Seen in Pediatric Patients (Attributable to Age, Gender, Body Weight, BSA, and Other Factors)

Pharmacologic FindingsDrug NameFindings According to Age, Gender, and/or Weight
Lower drug clearance (or apparent oral clearance) in younger patientsFluvoxamineLower apparent oral clearance in younger patients (age: 6–11 y); gender effect noted in clinical study (girls 8–11 y of age may benefit from lower doses)
FamotidineLower clearance in younger patients based on intravenous dose; after oral suspension dose, 0–3-mo-old patients had apparent oral famotidine clearance 50% less than that for older children and adults
LamivudineSubstantially reduced oral clearance in patients <3 mo of age, particularly 1-wk-old neonates
MethylphenidateApparent oral clearance reduced ∼40% in younger pediatric patients (age: 6–12 y), compared with adolescents
AmphetamineApparent oral clearance of amphetamine lower in pediatric patients (age: 6–12 y), compared with adolescents and adults
Drug clearance (or apparent oral clearance) increases with increasing body weight (up to adult values)Atovaquone/proguanilLower atovaquone and proguanil apparent oral clearance values for patients weighing <40 kg; recommended dosing of Malarone fixed-dose tablets based on body weight in pediatric patients from 11 kg to 40 kg; table describing dosage for treatment provided in labeling
FluoxetineDifferences in fluoxetine exposure between younger patients and adolescents explained by differences in body weight
LeflunomideLower clearance of M1 metabolite in patients weighing ≤40 kg
OndansetronOndansetron elimination half-life of ∼7 h in 1- to 4-mo-old pediatric patients, 3 h in 5-mo- to 12-y-old pediatric patients, and 5 h in adults
Higher apparent oral clearance in younger patientsGabapentinHigher apparent oral clearance in children 1 mo to <5 y of age
BenazeprilHigher apparent oral clearance in hypertensive pediatric patients (age: 6–12 y) and adolescents, compared with adults; terminal elimination half-life in children one third of that in adults
OxcarbazepineWeight-adjusted clearance of active metabolite is higher in younger pediatric patients and decreases as age and body weight increase, approaching adult values; in pediatric patients 1 mo to 4 y of age, weighing ∼11 kg, weight-normalized clearance of metabolite was approximately 2 times adult value
LevetiracetamBody weight-normalized apparent oral clearance of levetiracetam in 6- to 12-y-old pediatric patients ∼40% higher than that in adults
Apparent oral clearance and distribution volume increase with increasing BSASotalolSimilar exposure after corrections for dose and BSA except for smallest patients (BSA: <0.33 m2), who had greater exposure and response; additional monitoring and dose adjustment needed for those patients
OtheraRemifentanilClearance and volume of distribution higher and larger, respectively, in younger patients, compared with adolescents and adults; high variability in pharmacokinetics in neonatal patients, and individual dose titration recommended
NelfinavirHigh variability in pharmacokinetics confounded by variable food effect and food intake in pediatrics; dose not established for <2 y of age
  • a Pharmacokinetic/pharmacodynamic and safety information was obtained for tolterodine (Detrol); however, no indication was granted.