Children pharmacokinetics

Garnett, W.R. (1997) Lamotrigine pharmacokinetics./Child Neurol 12 (Suppl 1) S10-S15. 

Pharmacokinetic and pharmacodynamic issues in the acutely ill child have been sporadically addressed and deserve further evaluation. 

Ginsberg, G., D. Hattis, B. Sonawane, et al. 2002. Evaluation of child/adult pharmacokinetic differences from a database derived from the therapeutic drug literature. Toxicol. Sci. 66 185-200. 

Dose adjustment in hepatic Impairment The recommended dose of abacavir in patients with mild hepatic impairment (Child-Pugh score 5 to 6) is 200 mg twice daily. To enable dose reduction, use abacavir oral solution (10 ml twice daily) to treat these patients. The safety, efficacy, and pharmacokinetic properties of abacavir have not been established in patients with moderate to severe hepatic impairment therefore, abacavir is contraindicated in these patients. 

However, there is one more relatively recent development in pharmacokinetics, which is important to note. As we went through the measurement of the concentration-time curve for the single intravenous or oral dose, did you consider what the volunteer had to do He or she probably had to be at the laboratory without having had anything to eat, to have a cannula put into one of the forearm veins so that repeated blood samples could be withdrawn at regular intervals - usually up to and beyond 24 hours from dosing. You can see that this would just not be a possible thing to do in a sick child or an elderly patient with a major medical problem. So how do... 

The pharmacokinetics of stimulants are characterized by rapid absorption, low plasma protein binding, and quick extracellular metabolism (Patrick et al., 1987). Although some investigators claim that the dose-response relationship is affected by the child s weight, others have shown that individual dose-response stimulant effects are independent of the child s weight (Rapport et al., 1989). 

The recently introduced product Concerta is a once-a-day administration MPH delivery system called OROS (osmotically released). This delivery system creates an ascending plasma level pattern instead of the peak-and-valley pharmacokinetic profile seen in the IR preparations. Similar extended-delivery bead-technology, double-pulse preparations have been introduced for Metadate-CD at 10, 20, and 30 mg (Green-hill et ah, 2002, in press) for the spheroidal technology of Ritalin-EA, and for Adderall-XR preparations (McGough et ah, 2002, in press). Beaded stimulant preparations mix IR and delayed-release beads in a capsule. The patient can swallow the capsule whole or sprinkle the contents in food if pill taking is difficult for the child. 

Birmaher, B.B., Greenhill, L., Cooper, T., Fried, J., and Maminski, B. (1989) Sustained release methylphenidate pharmacokinetic studies in ADDH males. ] Am Acad Child Adolesc Psychiatry 28 768-772. 

Greenhill, L., Swanson, J., Steinhoff K, Tullock S, Clausen S, Zhang Y (2002 b), A pharmacokinetic/pharmacodynamic study comparing a single morning dose of Adderall to twice daily dosing in children with attention-deficit/hyperactivity disorder. J Am Acad Child Adolesc (in press). Psychiatry. 

Alderman, J., Wolkow, R., Chung, M., and Johnston, H.E (1998) Sertraline treatment of children and adolescents with obsessive-compulsive disorder or depression pharmacokinetics, tolerability, and efficacy. / Am Acad Child Adolesc Psychiatry 37 386-394. 

Geller, B., Cooper, T.B., Graham, D.L., Fetner, H.H., Marsteller, F.A., and Wells, J.M. (1992) Pharmacokinetically designed doubleblind placebo-controlled study of nottriptyline in 6- to 12-yeat-olds with major depressive disorder. / Am Acad Child Adolesc Psychiatry 31 34—44. 

In this chapter we review the mechanisms of action, pharmacokinetics, side effects, and uses of lithium and the anticonvulsants as they apply to child psychiatric clinical practice. 

Clein, P.D. and Riddle, M.A. (1995) Pharmacokinetics in children and adolescents. Child Adolesc Psychiatr Clin North Am 4 59-75. 

Findling, R.L., Reed, M.D., Myers, C., Riordan, M.A., Fiala, S., Branicky, L., Waldorf, B., and Blumer, J.L. (1999) Paroxetine pharmacokinetics in depressed children and adolescents. / Am Acad Child Adolesc Psychiatry 38 952-959. 

Labellarte, M., Zumbrunnen, T., Brennan,/., Biederman, J., Connor, J., Emslie, J., Ferguson, J., Khan, A., Ruckle, J., Sallee, R., and Riddle, M. (in press) Multiple-dose pharmacokinetics of fluvox-amine in children and adolescents. / Am Acad Child Adolesc Psychiatry. 

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. 

Hughes, C. and Preskorn, S. (1994) Pharmacokinetics in child/ado-lescent psychiatric disorders. Psychiatr Ann 24 76-82. 

Adderall XR (package insert). Wayne, PA, Shire US Inc, 2004 Angrist B, d Hollosy M, Sanfilipo M, et al Central nervous system stimulants as symptomatic treatments for AIDS-related neuropsychiatric impairment. J Clin Psychophamiacol 12 268—272, 1992 Arnold LE, Lindsay RL, Connors CK, et al A douhle-hlind, placebo-controlled withdrawal trial of dexmethylphenidate hydrochloride in children with attention-deficit hyperactivity disorder. I Am Acad Child Adolesc Psychiatry 14 542—554, 2004 Belle DJ, Ernest CS, Sauer JM, et al Effect of potent CYP2D6 inhibition by paroxetine on atomoxetine pharmacokinetics. I Clin Pharmacol 42 1219-1227, 2002... 

Whereas various childhood disorders have been reported to benefit from drug therapies, systematic data to support their use are usually minimal or lacking. An additional complication is the clinically significant pharmacokinetic (and perhaps pharmacodynamic) differences between the adult and younger age groups. Thus, the use of drugs in any treatment plan must be carefully considered and cautiously monitored to maintain the risk-benefit ratio in favor of the child or adolescent patient. 

Geller B, Cooper TB, Graham DL, et al. Pharmacokinetically designed double-blind placebo-controlled study of nortriptyline in 6 to 12 year-olds with major depressive disorder. J Am Acad Child Adolesc Psychiatry 1992 31 34-44. 

Clonidine is one of the most widely used sedating medications in pediatric and child psychiatry practice, particularly in children with sleep onset delay and ADHD. It is a central alpha2 agonist. Pharmacokinetics show rapid absorption, with an onset action within 1 h, peak effects at 2-4 h and a half-life 6-24 h. Effects on sleep architecture are fairly minimal but may include decreased REM, so that discontinuation can lead to REM rebound. Clonidine has a narrow therapeutic index, and there has been a recent dramatic increase in reports of overdose with this medication. Potentially significant side effects including hypotension, bradycardia, anticholinergic effects, irritability, and dysphoria rebound hypertension may occur on abrupt discontinuation. Tolerance often develops, necessitating increases in dose. 

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