Dose Optimization Based on Population Pharmacokinetic Modeling of High-Dose Cyclosporine, a P-glycoprotein Inhibitor, in Combination with Systemic Chemotherapy in Pediatric Patients with Retinoblastoma
| العنوان: | Dose Optimization Based on Population Pharmacokinetic Modeling of High-Dose Cyclosporine, a P-glycoprotein Inhibitor, in Combination with Systemic Chemotherapy in Pediatric Patients with Retinoblastoma |
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| المؤلفون: | Hyun-moon Back, Sandy Jeong Rhie, Jung Woo Han, Hwi-yeol Yun, Chuhl Joo Lyu, Eun Sun Son, Yoon Sun Ree, Ji Hyun Ahn |
| المصدر: | Journal of Ocular Pharmacology and Therapeutics. 34:647-655 |
| بيانات النشر: | Mary Ann Liebert Inc, 2018. |
| سنة النشر: | 2018 |
| مصطلحات موضوعية: | Male, Oncology, medicine.medical_specialty, Childhood malignancy, Pharmacokinetic modeling, Population, Population pharmacokinetics, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Electronic Health Records, Humans, Pharmacology (medical), ATP Binding Cassette Transporter, Subfamily B, Member 1, Child, education, Retrospective Studies, Pharmacology, P-glycoprotein Inhibitor, education.field_of_study, Dose-Response Relationship, Drug, business.industry, Retinoblastoma, Systemic chemotherapy, Data Collection, Infant, medicine.disease, eye diseases, Ophthalmology, Dose optimization, Child, Preschool, 030220 oncology & carcinogenesis, Cyclosporine, 030221 ophthalmology & optometry, Female, Ophthalmic Solutions, business |
| الوصف: | Retinoblastoma is a childhood malignancy of the retina. To increase the exposures of systemic chemotherapy, high-dose cyclosporine, as a P-glycoprotein modulating agent, has been combined with a standard chemotherapy. However, the effective and safe dose of cyclosporine has not been well evaluated. This study is to optimize cyclosporine dose using population pharmacokinetic modeling.Clinical data were obtained from 161 systemic chemotherapy cycles of 34 pediatric retinoblastoma patients between December 2006 and April 2015. Total 15 scenarios were simulated by 5 different doses (12, 14, 15, 17, and 20 mg/kg) of cyclosporine in 3 different weight groups (5-10, 10-15, and 15-20 kg). Numerical success ratio was obtained after assessing the simulated target cyclosporine concentration in the range of 2,000-2,500 ng/mL using NONMEM version 7.3 software.A final model was built based on a 1-compartment model with weight-normalized allometric scaling to minimize the variability of pediatric size. In simulations, numeric success ratio with 15 mg/kg/day and the above were higher than that of traditional doses in all of the scenario groups. No significant adverse responses were reported. Conclusion and Relevance: High-dose cyclosporine regimen as a P-gp modulator is required to improve the efficacy of systemic chemotherapy with caution in pediatric patients with retinoblastoma. Clearance, volume of distribution, and body weight are important parameters to consider in selecting adequate dosing regimen. |
| تدمد: | 1557-7732 1080-7683 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::b3af31eb560de0c3b4fdb5d83e00ebd1 https://doi.org/10.1089/jop.2018.0041 |
| حقوق: | CLOSED |
| رقم الأكسشن: | edsair.doi.dedup.....b3af31eb560de0c3b4fdb5d83e00ebd1 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15577732 10807683 |
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