Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Clinical Trial
, 59 (1), 43-53

Population Pharmacokinetics of Epinastine, a Histamine H1 Receptor Antagonist, in Adults and Children

Affiliations
Clinical Trial

Population Pharmacokinetics of Epinastine, a Histamine H1 Receptor Antagonist, in Adults and Children

A Sarashina et al. Br J Clin Pharmacol.

Abstract

Aims: Our objective was to develop a population pharmacokinetic (PPK) model for epinastine, a histamine H(1) receptor antagonist, in adults and children and to obtain pharmacokinetic information to support dosing recommendations in children.

Methods: A total of 1510 plasma samples were collected from 62 healthy adult volunteers and 62 paediatric atopic dermatitis patients. The data were analysed using the NONMEM program according to a two-compartment model with first-order absorption. In addition, the final PPK model was evaluated by means of bootstrapping resampling.

Results: The oral clearance (CL/F) was found to be associated with body weight, formulation and food status. The volume of distribution of the central compartment (V(1)/F) was related to body weight and food status. An absorption lag time was apparent in fed subjects. On the other hand, other covariates (formulation on V(1)/F, volume of distribution of the peripheral compartment (V(2)/F), first-order absorption rate constant (Ka) and absorption lag time (ALAG); food status on V(2)/F and Ka; body weight on V(2)/F) were not statistically significant. No effect of age on CL/F, V(1)/F or V(2)/F was found. The mean parameter estimates obtained with an additional 200 bootstrap replicates of data were within 90-117% of those obtained with the original data set. These results suggest that the pharmacokinetics of epinastine are similar in adults and in children, except for the effect of the difference of body weight. The result of the application of the PPK model to the clinical trial in paediatric patients, in which dosage was determined based on the body weight (from 14 kg to less than 24 kg; 10 mg dose, 24 kg or more; 20 mg dose), showed that the C(max) and AUC (25.6 +/- 6.9 ng ml(-1) and 246.8 +/- 68.2 ng h ml(-1)) were almost same levels with those of adults after administration of 20 mg (26.9 +/- 9.1 ng ml(-1) and 281.6 +/- 90.5 ng h ml(-1)).

Conclusions: A PPK model for epinastine was established and further evaluation by bootstrapping indicated that this model is stable. The model shows that, if dosage is adjusted based on the body weight, the epinastine exposure in paediatric patients is similar to that in adults.

Figures

Figure 1
Figure 1
Observed plasma concentrations and sampling times of epinastine in (A) healthy adults after the initial dose and (B) paediatric atopic dermatitis patients in the steady state
Figure 2
Figure 2
Plot of observed epinastine concentration vs. final model-predicted epinastine concentration. (A) predicted concentration and (B) individual predicted concentration in healthy adults; (C) predicted concentration and (D) individual predicted concentration in paediatric atopic dermatitis patients. The line represents the line of identity
Figure 3
Figure 3
Plots of weighted residuals vs. predicted concentrations (PRED). The horizontal line represents the zero level
Figure 4
Figure 4
Comparison of individual exposures to epinastine (A: Cmax, B: AUC) observed or calculated by the noncompartmental method vs. those predicted by Bayesian estimation based upon the final population pharmacokinetic model. The solid line represents the unit line
Figure 5
Figure 5
Typical plasma concentration-time profiles of epinastine in the steady state, simulated for various patient subgroups. (A) 10 mg dose as dry syrup in the fed state, 14 vs. 24 kg (B) 20 mg dose as dry syrup in the fed state, 40, 60, 80 kg (C) 20 mg dose as dry syrup in the fasted state vs. the fed state, 60 kg (D) 20 mg dose as tablet vs. dry syrup in the fed state, 60 kg
Figure 6
Figure 6
Comparison of individual exposures to epinastine (A: Cmax, B: AUC) predicted by Bayesian estimation based upon the final population pharmacokinetic model between adult (20 mg dose) and children (14 kg to less than 24 kg; 10 mg dose, 24 kg or more; 20 mg dose). 10 mg dose (•); 20 mg dose (○)

Similar articles

See all similar articles

Cited by 6 articles

See all "Cited by" articles

Publication types

Feedback