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Introduction: Loratadine (LOR) (Fig. 1), an active H1 receptor antagonist, is often used in the treatment of allergic disorders such as seasonal allergies and skin rash [1]. LOR was clinically approved for symptomatic relief of nasal and non-nasal symptoms of allergic rhinitis in children ≥2years. Materials and Methods: An adapted method of liquid chromatography-mass spectrometry (LC/MS/MS) was developed and validated to measure the concentrations of loratadine (LOR) and its active metabolite descarboethoxyloratadine (DCL) from pediatric plasma. After being mixed with the internal standard (IS, propranolol) and precipitated with methanol, samples were centrifuged and 20 μL of the supernatants were injected into the HPLC system. Separation was carried out on a reversed-phase C18 gradient column using a mobile phase consisting of water (containing 0.1 % formic acid) and acetonitrile. The flow rate was 0.5 mL/min and the running time was 5.0 min for each sample. Results and Conclusion: Quantitation of LOR, DCL and IS was performed using MRM mode and the transitions were: 383.1 → 337.1 for LOR, 311.1 → 259.0 for DCL and 260.2 → 116.0 for propranolol, respectively. The method was validated according to FDA guidelines, precisions and accuracies met the requirements in all cases. Calibration curves were 0.2–50.0 ng/mL for both LOR and DCL. This method was then applied for a pilot study examining the pharmacokinetics and therapeutic drug monitoring of LOR in children.

Qian Li,1,2,* Kai Wang,3,* Hai-Yan Shi,2 Yue-E Wu,1 Yue Zhou,1 Min Kan,1 Yi Zheng,1 Guo-Xiang Hao,1 Xin-Mei Yang,2 Yi-Lei Yang,2 Le-Qun Su,2 Xiao-Ling Wang,4 Evelyne Jacqz-Aigrain,5,6 Jun Zhou,7,* Wei Zhao1,2,* 1Department of Clinical Pharmacy, School of Pharmaceutical Sciences, Shandong University, Jinan, People’s Republic of China; 2Department of Pharmacy, Shandong Provincial Qianfoshan Hospital, The First Affiliated Hospital of Shandong First Medical University, Jinan, People’s Republic of China; 3Department of Respiratory Disease, Shandong Provincial Qianfoshan Hospital, The First Affiliated Hospital of Shandong First Medical University, Jinan, People’s Republic of China; 4Clinical Research Center, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing, People’s Republic of China; 5Department of Pediatric Pharmacology and Pharmacogenetics, Hôpital Robert Debré, AP-HP, Paris, France; 6University Paris Diderot, Sorbonne Paris-Cité, Paris, France; 7Clinical Training Center, Shandong Provincial Qianfoshan Hospital, The First Affiliated Hospital of Shandong First Medical University, Jinan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jun ZhouClinical Training Center, Shandong Provincial Qianfoshan Hospital, The First Affiliated Hospital of Shandong First Medical University, 16766 Jing Shi Street, Jinan 250014, People’s Republic of ChinaTel/Fax +86 531 8237 3200Email zhoujun_jn@163.comWei ZhaoDepartment of Clinical Pharmacy, School of Pharmaceutical Sciences, Shandong University, 44 Culture West Road, Jinan 250012, People’s Republic of ChinaTel/Fax +86 531 8838 3308Email zhao4wei@hotmail.comBackground: Montelukast, a potent oral selective leukotriene-receptor antagonist, inhibits the action of cysteinyl-leukotriene in patients with asthma. Although pharmacokinetic studies of montelukast have been reported in Caucasian adults and children, and showed large inter-individual variability on pharmacokinetics, none of these studies has been explored in Chinese children. Given the potential inter-ethnic difference, the purpose of the present study was to evaluate the effects of developmental factors and pharmacogenetics of CYP2C8 and SLCO2B1 on montelukast clearance in Chinese pediatric patients.Methods: After the administration of montelukast, blood samples were collected from children and plasma concentrations were determined using an adapted micro high-performance liquid chromatography coupled with the fluorescence detection (HPLC-FLD) method. A previously published pharmacokinetic model was validated using the opportunistic pharmacokinetic samples, and individual patient’s clearance was calculated using the validated model. Population pharmacokinetic analysis was performed using a nonlinear mixed-effects model approach (NONMEM V 7.2.0) and variants of CYP2C8 and SLCO2B1 were genotyped.Results: Fifty patients (age range: 0.7–10.0 years) with asthma were enrolled in this study. The clearance of montelukast was significantly higher in children with the SLCO2B1 c.935GA and c.935AA genotypes compared with that of children with the SLCO2B1 c.935GG genotype (0.94 ± 0.26 versus 0.77 ± 0.21, p = 0.020). The patient’s weight was also found to be significantly corrected with montelukast clearance (p