1. Population pharmacokinetics of imipramine in children
- Author
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M. M. Fernández de Gatta, M. Tamayo, María Josefa Bernalte García, and Alfonso Domínguez-Gil
- Subjects
Male ,medicine.medical_specialty ,Imipramine ,Adolescent ,Metabolite ,Population ,Population pharmacokinetics ,Pharmacology ,Models, Biological ,Hospitals, University ,chemistry.chemical_compound ,Pharmacokinetics ,Internal medicine ,Desipramine ,medicine ,Outpatient clinic ,Humans ,Pharmacology (medical) ,education ,Child ,Active metabolite ,Demography ,education.field_of_study ,business.industry ,General Medicine ,Endocrinology ,chemistry ,Spain ,Female ,business ,human activities ,Algorithms ,medicine.drug - Abstract
The population pharmacokinetics of imipramine (IMI) and its active metabolite desipramine (DMI) have been evaluated using 177 IMI and DMI serum levels from 49 enuretic children (6-13 y) on IMI treatment. Standard two stage (STS) and maximum likelihood (ML) methods were used to estimate fixed and random effect parameters of IMI. Simultaneous estimation of the drug and metabolite parameters was carried out by the STS method. The mean value of the elimination constant of the drug and metabolite were 0.0425 h-1 and 0.0359, h-1 respectively. Significantly higher variability was found in the pharmacokinetic parameters of the metabolite. According to these estimated pharmacokinetic parameters, the recommended dose for enuretic children should be 1.7 mg.kg-1.day-1. The population pharmacokinetic parameters obtained in the study permit dosage individualisation using a bayesian algorithm.Researchers used population pharmacokinetic parameters and data on the concentration effect relationship from 49 6-13 year old children suffering from enuresis who attended an outpatient psychiatric clinic at University Clinical Hospital in Salamanca, Spain to design rational dosing guidelines of the antidepressant imipramine (IMI) for individual patients. They evaluated 177 IMI serum levels and IMI's active metabolite desipramine (DMI) serum levels. The researchers used standard 2-stage (STS) and maximum likelihood methods to conduct the population pharmacokinetic analysis of IMI. They used STS to simultaneously estimate IMI and DMI parameters. The average value of IMI's elimination constant stood at 0.0425 h-1 and that of DMI's elimination constant stood at 0.0359 h-1. The researchers observed more variability in pharmacokinetic parameters of DMI than those of IMI. Based on estimated pharmacokinetic parameters, a dose of 1.7 mg kg-1 day-1 IMI is needed in children to reach the total serum level of 80 ng/ml which was higher than the dose generally administered in clinical practice (1 mg kg-1 day-1). The researchers demonstrated that applying the population pharmacokinetic parameters to Bayesian fitting methods allows clinicians to individualize IMI dose in children. more...
- Published
- 1992