Pichini Simona, Papaseit Esther, Joya Xavier, Vall Oriol, Farré Magí, Garcia-Algar Oscar, de laTorre Rafael
Department of Therapeutic Research and Medicines Evaluation, Istituto Superiore di Sanitá, V.le Regina Elena 299, Rome 00161, Italy.
Ther Drug Monit. 2009 Jun;31(3):283-318. doi: 10.1097/FTD.0b013e31819f3328.
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.
儿科(0至14岁)的治疗药物监测(TDM)尤为重要,因为药物的吸收、分布、代谢和排泄以及药物药代动力学特征可能与成人不同。在这种情况下,儿童体内药物消除半衰期(t(1/2))、血浆峰浓度(Cmax)、曲线下面积、清除率(CL)、达峰时间(Tmax)以及剂量/浓度关系等多个参数可能与成人不同。因此,了解药代动力学参数以及药物浓度的治疗和中毒范围有助于临床医生优化儿科患者的药物治疗方案。精神药物的TDM需要特别关注,因为剂量使用不当、依从性差以及过量使用可能产生毒性作用所带来的药理和临床后果。苯二氮䓬类、抗癫痫药物、三环类抗抑郁药、选择性5-羟色胺再摄取抑制剂、抗精神病药物、精神兴奋剂(注意力缺陷多动障碍药物)、阿片类镇痛药和抗偏头痛药物等精神活性药物是一组异类药物。这些药物存在个体差异,因此,必须对这些药物TDM的效用进行个体评估。由于包括精神疾病在内的合并症的出现,联合药物治疗的使用并不罕见。因此,这些患者可能面临多种潜在药物相互作用的风险。儿科人群中TDM的实施比成人更困难,因为一些采样程序具有侵入性,会给儿童带来不适,此外,还需要患者的配合。将提供几个例子,建议使用替代基质,如唾液,以尽量减少不便和患者不适。