Pharmacokinetics pediatric patients

Drug Studies in Pediatric Patients Medical Officer s Review Statistical Review Evaluation Chemistry, Manufacturing and Controls CDER Labeling and Nomenclature Committee Clinical Pharmacology/Biopharmaceutics Microbiologist s Review Pharmacokinetics Review Carcinogenicity Assessment... 

Renal impairment Data in pediatric patients with impaired renal function are not available however, because cefepime pharmacokinetics are similar in adult and pediatric patients, changes in dosing regimen similar to those in adults are recommended for pediatric patients. 

The pharmacokinetics of meropenem in pediatric patients 2 years of age and oider are essentiaiiy simiiar to those in aduits. In infants and chiidren 2 months to 12 years of age, no age- or dose-dependent effects on pharmacokinetic parameters were observed. Mean haif-iife was 1.13 hours, mean voiume of distribution at steady state was 0.43 L/kg, mean residence time was 1.57 hours, ciearance was 5.63 mL/min/kg and renai ciearance was 2.53 mL/min/kg. The eiimination haif-iife is siightiy proionged (1.5 hours) in pediatric patients 3 months to 2 years of age. 

The safety, efficacy, and pharmacokinetics of nelfinavir have not been evaluated in pediatric patients younger than 2 years of age. 

Children Two hundred fifty-one patients 4 years of age and above have received amprenavir as single or multiple doses in studies. An adverse event profile similar to that seen in adults was seen in pediatric patients. The safety, efficacy, and pharmacokinetics of amprenavir capsules have not been evaluated in pediatric patients below 4 years of age. 

Children-The pharmacokinetics of didanosine administered as Videx EC has not been studied in pediatric patients. 

Children Use of stavudine in pediatric patients is supported by evidence from adequate and well-controlled studies of stavudine in adults with additional pharmacokinetic and safety data in pediatric patients. 

Battino D, Estienne M, Avanzini G. Clinical pharmacokinetics of antiepUeptic drugs in pediatric patients. Chn Phannacokin 1995 29 341-69. 

Wilens, TE. (2001) Pharmacokinetics of fluoxetine pediatric patients (personal communication). 

Valproic acid is eliminated by first-order kinetics and has an elimination half-life of 5-20 hours (average, 10.6 hours). Pediatric patients (3 months to 10 years) have a 50% higher clearance of the drug expressed by weight (i.e., mL/min/kg) over the age of 10 years, pharmacokinetic parameters of valproic acid approximate those in adults (Cloyd et al., 1993). Valproic acid is metabolized principally in the liver by (3 (over 40%) and CO oxidation (up to 15%-20%). Thirty through 50% of an administered dose is excreted as glucuron-ide conjugates (Cloyd et al., 1993). 

Wilens T, Cohen LG, Beiderman J, Abrams A, neft D, Melnick K, Kurtz D, and Sinha V (2000, poster). Pharmacokinetics of fluoxetine in pediatric patients. Scientific Proceedings of the 47th Annual Meeting of The American Academy of Child And Adolescent Psychiatry. October 24-29, 2000). New York, NY. 

As of the date of this chapter (circa March, 2002), labeling changes regarding pediatric use have resulted from only two programs—the study of buspirone in pediatric GAD and a pharmacokinetic study of fluvoxamine in pediatric OCD (fluvoxamine already had a controlled clinical trial in pediatric patients). Two placebo-controlled trials with buspirone in pediatric GAD did not reveal a treatment effect, and this negative outcome is reflected in Buspar labeling. A pharmacokinetic study of fluvoxamine dosed at 100 mg bid in pediatric... 

Pharmacokinetics Serum levels considered therapeutic (40pg/ml or greater) are achieved in most high-risk infants on intramuscular administration of the recommended dose. In studies in adult volunteers, palivizumab had a pharmacokinetic profile similar to a human IgGi antibody in regard to the volume of distribution and the half-life (mean 18 days). In pediatric patients less than 24 months of age, the mean half-life of palivizumab was 20 days. 

Battino, D., Estienne, M. and Aanzini, G. Clinical pharmacokinetics of anti-epileptic drugs in pediatric patients. Clin. Pharmacokinetics 29 (1995) 341-369. 

The in silico prediction of pharmacokinetic behavior in pediatric patients indicated the complexity of age related changes such that the clearance of drugs metabolized by the same enzymes took different patterns (Fig. 16.6), possibly due to other elements of PK such as differences in protein binding, red blood cell distribution, etc. 

Using the PPK approach in the development of a new drag has the advantage that the relevant pharmacokinetic parameters for a reasonably large population can be obtained from only a few blood samples per subject. The PPK approach is the method of choice in all situations when only sparse and unbalanced data can be obtained. This situation exists when the PK needs to be studied in elderly, critically ill and pediatric patients, but also very often in preclinical studies investigating the effects of the drug in animals. 

Table 2 gives therapeutic serum concentrations and pharmacokinetic information for some drugs administered to pediatric patients. 

Lugo Goytia G, Lares-Asseff I, Perez Guille MG, Perez AG, Mejia CL. Relationship between clinical and biologic variables and chloramphenicol pharmacokinetic parameters in pediatric patients with sepsis. Ann Pharmacother 2000 34(3) 393-7. 

Brammer KW, Coates PE. Pharmacokinetics of fluconazole in pediatric patients. Eur J Clin Microbiol Infect Dis 1994 13(4) 325-9. 

Groll AH, Wood L, Roden M, Mickiene D, Chiou CC, Townley E, Dad L, Piscitelli SC, Walsh TJ. Safety, pharmacokinetics, and pharmacodynamics of cyclodextrin itraconazole in pediatric patients with oropharyngeal candidiasis. Antimicrob Agents Chemother 2002 46(8) 2554-63. 

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