title: Population pharmacokinetics of pranlukast hydrate dry syrup in children with allergic rhinitis and bronchial asthma.
abstract: This study aimed to assess the steady-state pharmacokinetics of pranlukast, a leukotriene receptor antagonist, in children with allergic rhinitis and bronchial asthma, and to clarify factors affecting apparent clearance (CL/F). A total of 192 plasma samples were obtained from 98 children (rhinitis 64, asthma 13, complications 21), aged 3-14 years in 2 clinical trials. Plasma concentration of pranlukast was determined by liquid chromatography connected with a tandem mass spectrometer and analyzed by a population approach using NONMEM program. The plasma concentration-time course of pranlukast was described by using a one-compartment model with the first-order absorption and lag time. The robustness of the population pharmacokinetic model was evaluated by using 200 bootstrap samples. The results of population pharmacokinetic analysis showed that only age was a factor affecting the CL/F per body weight, with CL/F decreasing with increasing age. No significant variation was seen in the CL/F between rhinitis and asthma. The interindividual variability in the CL/F and the residual variability were 19.7% and 48.4%, respectively. All the parameters fell within 10% of the bootstrapped mean. In conclusion, the results show that age is the most influential factor for explaining interindividual variability in CL/F, and the difference in diseases does not affect CL/F.
authors.affiliation: Pharmacokinetic Research Institute, Ono Pharmaceutical Co., Ltd., Wadai Tsukuba, Ibaraki, Japan. s.nakade@ono.co.jp
authors.forename: Susumu
authors.initials: S
authors.lastname: Nakade
authors.forename: Shinya
authors.initials: S
authors.lastname: Ueda
authors.forename: Tomoya
authors.initials: T
authors.lastname: Ohno
authors.forename: Kazuki
authors.initials: K
authors.lastname: Nakayama
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Miyata
authors.forename: Eiji
authors.initials: E
authors.lastname: Yukawa
authors.forename: Shun
authors.initials: S
authors.lastname: Higuchi
mesh_terms: D000293:Adolescent; D000465:Algorithms; D018927:Anti-Asthmatic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001249:Asthma / Q000378:metabolism*; D002648:Child; D002675:Child, Preschool; D002867:Chromones / Q000008:administration & dosage / Q000493:pharmacokinetics*; D003627:Data Interpretation, Statistical; D005260:Female; D006801:Humans; D008297:Male; D015233:Models, Statistical; D019999:Pharmaceutical Solutions; D015203:Reproducibility of Results; D006255:Rhinitis, Allergic, Seasonal / Q000378:metabolism*
chemical_list: D018927:Anti-Asthmatic Agents; D002867:Chromones; D019999:Pharmaceutical Solutions; C047681:pranlukast