Pharmacokinetics and Therapeutic Drug Monitoring of Psychotropic Drugs in Pediatrics

Abstract

Therapeutic drug monitoring (TDM) in pediatrics (0-14 years) is especially important because the absorption, distribution, metabolism, and excretion of drugs and drug pharmacokinetic profiles can be different from that of the adult population. In this context, several parameters like half-life of drug elimination from the body (t(1/2)), peak plasma concentration (Cmax), area under the curve, clearance (CL), Tmax, and dose/concentration relationship in children may differ from adults. Hence, the knowledge of pharmacokinetic parameters and therapeutic and toxic ranges of drug concentrations may help the clinicians to optimize drug treatment regimens in the pediatric population. TDM of psychotropic drugs requires particular attention for the pharmacological and clinical consequences of nonadequate dose use, lack in the compliance, and overdoses with possible toxic effects. Psychoactive drugs such as benzodiazepines, antiepileptic drugs, tricyclic antidepressants, selective serotonin reuptake inhibitors, antipsychotic drugs, psychostimulants (attention-deficit hyperactivity disorder drugs), opioid analgesics, and antimigraine drugs are a heterogeneous group. These drugs are subject to interindividual variability, and therefore, the usefulness of TDM for these drugs has to be assessed individually. Because of the occurrence of comorbid pathologies, including psychiatric disorders, the use of combined pharmacotherapy is not uncommon. As a consequence, these patients may be at risk from a number of potential drug-drug interactions. The implementation of TDM in pediatric population is more difficult than in adults because some sampling procedures are invasive and cause discomfort in children, and additionally, they require the cooperation of the patient. Several examples will be provided where the use of alternative matrices, such as saliva, is proposed to minimize inconvenience and patient discomfort.

Pharmacokinetics of methylphenidate in oral fluid and sweat of a pediatric subject

“…Testing in oral fluid and sweat could be used as alternatives to blood testing not only for purposes of drug monitoring [5,6] and pharmacokinetic studies [7][8][9] but also for the detection of illicit drug use [10][11][12]. Specifically, these two matrices can be used to monitor recent use and misuse of MPH in children, adolescents and young adults [13][14][15].…”

Guidelines for Monitoring and Management of Pediatric Patients Before, During, and After Sedation for Diagnostic and Therapeutic Procedures: Update 2016

“…[300][301][302][303][304] Medications used to treat HIV infection, some anticonvulsants, immunosuppressive drugs, and some psychotropic medications (often used to treat children with autism spectrum disorder) may also produce clinically important drugdrug interactions. [305][306][307][308][309][310][311][312][313][314] Therefore, a careful drug history is a vital part of the safe sedation of children. The practitioner should consult various sources (a pharmacist, textbooks, online services, or handheld databases) for specific information on drug interactions.…”

Correlation Between Methylphenidate and Ritalinic Acid Concentrations in Oral Fluid and Plasma

“…Hence, the use of alternative biological matrices should be considered for noninvasive assessment of drug use. Testing of oral fluid has been used successfully as an alternate to blood testing for psychotropic drugs in therapeutic drug monitoring (1 ), pharmacokinetic studies (2)(3)(4), and the detection of drug misuse (5,6 ). Specifically, weak basic drugs such as amphetamine derivatives have been reported to concentrate in oral fluid because their pH is slightly acidic compared with that of plasma (3,7 ).…”