Special Pharmacokinetic Considerations in Children

Abstract

Pediatric patients have greater degrees of pharmacokinetic variability and unpredictability than adults. This variability results from the effects of pharmacogenetics, age and growth, prior and current comedication, and disease. Newborns with seizures have the least predictable dosage requirements, and their needs change as drug-eliminating mechanisms mature in the neonatal period. Infants have the highest relative capacities to eliminate antiepileptics of any age group and require the largest relative doses. In addition to age-related trends, children demonstrate the same drug-specific, pharmacokinetic phenomena that adults do, including nonlinear phenytoin elimination, nonlinear valproate binding, and autoinduction of carbamazepine. Intercurrent illness and drug interactions further modify the age-related pharmacokinetic patterns in children and make dosage requirements even more unpredictable. Recent studies have shown that febrile illness can affect drug elimination, sometimes decreasing drug levels by 50% or more. Intermittent treatment with benzodiazepines administered either orally or rectally can be an important adjunct and help minimize this type of problem for children with marginally controlled epilepsy. Intermittent benzodiazepines are also helpful for children who have febrile seizures and who need only occasional antiepileptic protection.

Linezolid- and Vancomycin-Resistant Enterococcus Faecium Peritonitis and Bacteremia Successfully Treated With Daptomycin in an Immunocompromised Pediatric Patient With Hepatic and Renal Failure

“…In addition, drug clearance in general is expected to be higher in young children. 4,5 Daptomycin serum concentrations were assessed before hemodialysis by high-performance liquid chromatography after the dose was increased to 8 mg/kg (Table 1). No serum concentration was assessed immediately after the hemodialysis.…”

Anticonvulsants and Breast Feeding

“…The excretion of carbamazepine into breast milk was studied in the late 1970s and early 1980s (table I). [1,7,8,[31][32][33][34][35][36][37][38][39][40][41][42][43][44][45][46][47][48][49][50] Analysis of the results of all studies shown in table I indicates that the M/P ratio ranges from 0.17 to 0.69. Some of the typical studies by Pynnonen and Sillanpaa [31] and Niebyl et al [32] reported the M/P ratio to be 0.4 to 0.5.…”

“…Weighing the benefits of breast feeding against the potential risk of the medication, most of the studies considered carbamazepine as safe for use during breast feeding. [2,3,8,[31][32][33][34][35][36][37][38][39][42][43][44][45][47][48][49][50][51][52]68,69] There are few published case reports describing adverse events for carbamazepine in the breast-fed infant. Frey et al [70] reported a transient cholestatic jaundice in association with maternal carbamazepine treatment during pregnancy and lactation.…”

“…[86][87][88] The authors who reviewed the pharmacokinetic characteristics of valproic acid in breast milk found the drug to be safe for breast feeding. [1][2][3]7,8,[42][43][44][45][47][48][49][50][51][52][53][54][55][56] The American Academy of Pediatrics considers the drug as compatible with breast feeding, [58,59] and Bennett [56] indicates that it 'would appear to be safe'.…”

“…[60][61][62] The M/P ratio ranged from 0.03 to 0.55, with maximal dose to the infant ranging from 0.03 to 0.47 mg/kg/day (table I). [1,7,8,[40][41][42][43][44][45][46][47][48]50,59,[60][61][62][63][64] The average amount of phenytoin that a breast-fed infant would ingest in a day, calculated on the basis of these data, was between 0.5 and 4.8% (maximum 8.9%) of the weight-adjusted maternal daily dose. [64] The pharmacokinetics of phenytoin during lactation have been reviewed by Nau et al [44] The authors concluded that only a minimal risk to the breast-fed infant was present if maternal concentrations remained in the therapeutic range.…”