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Qualification and application of liquid chromatography-quadrupole time-of-flight mass spectrometric method for the determination of carisbamate in rat plasma and prediction of its human pharmacokinetics using physiologically based pharmacokinetic modeling

Translational and Clinical Pharmacology 2020년 28권 3호 p.147 ~ 159
이병일, 임정현, 박민호, 신석호, 변진주, 최장미, 박서진, 박민재, 박유리, Shin Young-G.,
소속 상세정보
이병일 ( Lee Byeong-Ill ) - Chungnam National University College of Pharmacy
임정현 ( Lim Jeong-Hyeon ) - Chungnam National University College of Pharmacy
박민호 ( Park Min-Ho ) - Chungnam National University College of Pharmacy
신석호 ( Shin Seok-Ho ) - Chungnam National University College of Pharmacy
변진주 ( Byeon Jin-Ju ) - Chungnam National University College of Pharmacy
최장미 ( Choi Jang-Mi ) - Chungnam National University College of Pharmacy
박서진 ( Park Seo-Jin ) - Chungnam National University College of Pharmacy
박민재 ( Park Min-Jae ) - Chungnam National University College of Pharmacy
박유리 ( Park Yu-Ri ) - Chungnam National University College of Pharmacy
 ( Shin Young-G. ) - Chungnam National University College of Pharmacy

Abstract


Carisbamate is an antiepileptic drug and it also has broad neuroprotective activity and anticonvulsant reaction. In this study, a liquid chromatography-quadrupole time-of-flight mass spectrometric (LC-qTOF-MS) method was developed and applied for the determination of carisbamate in rat plasma to support in vitro and in vivo studies. A quadratic regression (weighted 1/concentration2), with an equation y = ax2 + bx + c, was used to fit calibration curves over the concentration range from 9.05 to 6,600 ng/mL for carisbamate in rat plasma. Preclinical in vitro and in vivo studies of carisbamate have been studied through the developed bioanalytical method. Based on these study results, human pharmacokinetic (PK) profile has been predicted using physiologically based pharmacokinetic (PBPK) modeling. The PBPK model was optimized and validated by using the in vitro and in vivo data. The human PK of carisbamate after oral dosing of 750 mg was simulated by using this validated PBPK model. The human PK parameters and profiles predicted from the validated PBPK model were similar to the clinical data. This PBPK model developed from the preclinical data for carisbamate would be useful for predicting the PK of carisbamate in various clinical settings.

키워드

Qualification; LC-MS; Carisbamate; PBPK Modeling

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