Prediction of Imipramine Serum Levels in Enuretic Children by a Bayesian Method

Gatta, M. M. Fernández de; Tamayo, M.; García, M J; Amador, Dolly; Rey, Francisco Escobar del; Gutiérrez, J.; Hurlé, Alfonso Domínguez-Gil

doi:10.1097/00007691-198911000-00004

Cited by 6 publications

(2 citation statements)

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“…Dose prediction based on pediatric priors necessitates repeated measures. Bayesian approaches for dose predictions based on prior PK data obtained in pediatric patients have been performed for imipramine and desipramine, 75 gentamicin, 76 theophylline, 77 cefuroxime, 78 chloramphenicol, 79 vancomycin, 80 and digoxin. 32 These dose predictions, however, have not been tested in clinical trials nor have they been used in CTS settings to evaluate and/or optimize design elements.…”

Section: E481mentioning

confidence: 99%

Population pharmacokinetic studies in pediatrics: Issues in design and analysis

Meibohm

Läer

Panetta

et al. 2005

AAPS J

165

144

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The current review addresses the following 3 frequently encountered challenges in the design and analysis of population pharmacokinetic studies in pediatrics: (1) body size adjustments during the development of pharmacostatistical models, (2) design and validation of limited sampling strategies, and (3) the integration of historical priors in data analysis and trial simulation. Size adjustments with empiric approaches based on body weight or body surface area have frequently proven as a pragmatic tool to overcome large size differences in a pediatric study population. Allometric size adjustments, however, provide a more mechanistic, physiologically based approach that, if used a priori, allows delineation of the effect of size from that of other covariates that show a high degree of collinearity. The frequent lack of dense data sets in pediatric clinical pharmacology because of ethical and logistic constraints in study design can be overcome with the application of D-optimality-based limited sampling schemes in combination with Bayesian and nonlinear mixed-effects modeling approaches. Empirically based dose selection and clinical trial designs for pediatric clinical pharmacology studies can be improved by applying clinical trial simulation techniques, especially if they integrate adult and pediatric in vitro and/or in vivo data as historic priors. Although integration of these concepts and techniques in population pharmacokinetic analyses is not only limited to pediatric research, their application allows researchers to overcome some major hurdles frequently encountered in pharmacokinetic studies in pediatrics and, thus, provides the basis for additional clinical pharmacology research in this previously insufficiently studied fraction of the general population.

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Section: E481mentioning

confidence: 99%

Population pharmacokinetic studies in pediatrics: Issues in design and analysis

Meibohm

Läer

Panetta

et al. 2005

AAPS J

165

144

View full text Add to dashboard Cite

show abstract

“…Previous experience [10,11] of therapeutic drug monitoring of IMI in enuretic children and the increasing amount of information about serum levels data, led to the present application of population pharmacokinetic analysis to this population.…”

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confidence: 99%

Population pharmacokinetics of imipramine in children

Tamayo

Gatta

García

et al. 1992

Eur J Clin Pharmacol

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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.

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Sources of Prediction Error When Using a Bayesian Method to Evaluate Nortriptyline Serum Concentrations

Kehoe¹,

Harralson²,

Jacisin³

et al. 1994

The Journal of Clinical Pharma

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A Bayesian method was used to evaluate nortriptyline (NTP) serum concentrations (Cps) and predict future Cps in two populations: five simulated groups (n = 20 each) with known clearance (CL) and volume of distribution (Vd), and an actual inpatient group (n = 20). The effects of weight, CL, Vd, and magnitude of Cps on absolute prediction error (APE) were evaluated. In simulated groups, Cps after two doses of NTP and for steady-state were calculated for normal, increased, and decreased Vd and CL. In the actual patient group, Cps were measured in the first few days after starting NTP administration and again during maintenance therapy. The first Cps were used in the Bayesian program to estimate CL and Vd to predict the second Cps. In the simulated group, PE and APE differed significantly between normal and decreased values of CL. A large Vd resulted in less of a change in PE or APE in these subjects, but when combined with low CL led to the largest errors. In the actual patient group, PE was -5.9 +/- 19.2 ng/mL and APE was 15.4 +/- 12.6 ng/mL. In these patients, only body weight was correlated with the percent APE (r = 0.607, P = 0.005). The Bayesian method performs well clinically, but increased Vd and decreased CL can lead to higher PE. Clinically, the only factor that predicted higher APE was obesity. This may reflect an effect on Vd, and in these patients, a high APE may occur.

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Prediction of Imipramine Serum Levels in Enuretic Children by a Bayesian Method

Cited by 6 publications

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Population pharmacokinetic studies in pediatrics: Issues in design and analysis

Population pharmacokinetic studies in pediatrics: Issues in design and analysis

Population pharmacokinetics of imipramine in children

Sources of Prediction Error When Using a Bayesian Method to Evaluate Nortriptyline Serum Concentrations

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