Population pharmacokinetics of epinastine, a histamine H1 receptor antagonist, in adults and children
Open Access
- 16 December 2004
- journal article
- clinical trial
- Published by Wiley in British Journal of Clinical Pharmacology
- Vol. 59 (1), 43-53
- https://doi.org/10.1111/j.1365-2125.2005.2250
Abstract
Aims Our objective was to develop a population pharmacokinetic (PPK) model for epinastine, a histamine H1 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 (V1/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 V1/F, volume of distribution of the peripheral compartment (V2/F), first‐order absorption rate constant (Ka) and absorption lag time (ALAG); food status on V2/F and Ka; body weight on V2/F) were not statistically significant. No effect of age on CL/F, V1/F or V2/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 (from14 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.Keywords
This publication has 8 references indexed in Scilit:
- International Conference on Harmonisation; guidance on E11 clinical investigation of medicinal products in the pediatric population; availability. Notice.2000
- Epinastine: An update of its pharmacology, metabolism, clinical efficacy and tolerability in the treatment of allergic diseasesDrugs of Today, 2000
- Stability and Performance of a Population Pharmacokinetic ModelThe Journal of Clinical Pharmacology, 1997
- Positron emission tomographic study of central histamine H1-receptor occupancy in human subjects treated with epinastine, a second-generation antihistamine.1995
- Histamine H1 receptor occupancy in human brains after single oral doses of histamine H1 antagonists measured by positron emission tomographyBritish Journal of Pharmacology, 1995
- Chronopharmacological Study of a Nonsedative H1-blocking Agent (WAL 801 CL, Epinastine).Rinsho yakuri/Japanese Journal of Clinical Pharmacology and Therapeutics, 1991
- In vitro and in vivo studies of the non-sedating antihistamine epinastine.1988