Novel modeling approach integrating population pharmacokinetics and interspecies scaling to predict human pharmacokinetics of the new anti-tuberculosis agent telacebec (Q203)
Telacebec is a new anti-tuberculosis agent with promising therapeutic activity and a favorable safety profile. This study aimed to characterize the pharmacokinetics of telacebec via interspecies scaling and population pharmacokinetic modeling for the prediction of human pharmacokinetics. Preclinical...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-11-01
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| Series: | Biomedicine & Pharmacotherapy |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0753332223012398 |
| _version_ | 1797660563727187968 |
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| author | Jeongjun Kim Tae Hwan Kim Jinho Choi Kiyean Nam Beom Soo Shin Soyoung Shin |
| author_facet | Jeongjun Kim Tae Hwan Kim Jinho Choi Kiyean Nam Beom Soo Shin Soyoung Shin |
| author_sort | Jeongjun Kim |
| collection | DOAJ |
| description | Telacebec is a new anti-tuberculosis agent with promising therapeutic activity and a favorable safety profile. This study aimed to characterize the pharmacokinetics of telacebec via interspecies scaling and population pharmacokinetic modeling for the prediction of human pharmacokinetics. Preclinical pharmacokinetic data were obtained from mice, rats, and dogs following intravenous and oral doses of telacebec. A population pharmacokinetic model was developed to describe the pharmacokinetic data from all three species. The disposition parameters were well correlated with the body weight for all species using an allometric equation. Thus, the allometric scaling was incorporated into the population pharmacokinetic model, which could simultaneously describe the plasma concentration vs. time data from all preclinical studies as well as the Phase 1A clinical study. The developed model was used to predict the pharmacokinetics of telacebec after IV injection, including the clearance (CL) of 168.58 [118.86 – 238.73] mL/min and volume of distribution (Vss) of 968.84 [396.87 – 2831.31] L for 80-kg human. The absolute bioavailability of telacebec in humans in the fed state was estimated as 70.34 ± 9.91%. Finally, the population pharmacokinetic model with allometric scaling was utilized to simulate the plasma concentration vs. time profiles of telacebec after multiple oral doses in humans. The model-predicted profiles well agreed with the observed data in Phase 1B clinical trial. The present pharmacokinetic model may help better understand the activity of telacebec, leading to the design of optimal dosing regimens and new formulation development. |
| first_indexed | 2024-03-11T18:31:43Z |
| format | Article |
| id | doaj.art-378b4a65abc24722af03661f79d0571e |
| institution | Directory Open Access Journal |
| issn | 0753-3322 |
| language | English |
| last_indexed | 2024-03-11T18:31:43Z |
| publishDate | 2023-11-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Biomedicine & Pharmacotherapy |
| spelling | doaj.art-378b4a65abc24722af03661f79d0571e2023-10-13T11:02:37ZengElsevierBiomedicine & Pharmacotherapy0753-33222023-11-01167115441Novel modeling approach integrating population pharmacokinetics and interspecies scaling to predict human pharmacokinetics of the new anti-tuberculosis agent telacebec (Q203)Jeongjun Kim0Tae Hwan Kim1Jinho Choi2Kiyean Nam3Beom Soo Shin4Soyoung Shin5School of Pharmacy, Sungkyunkwan University, 2066 Seobu-ro, Jangan-gu, Suwon, Gyeonggi 16419, Republic of Korea; Qurient Co., Ltd., C-dong-801, PDC, 242, Pangyo-ro, Bundang-gu, Seongnam, Gyeonggi 13487, Republic of KoreaCollege of Pharmacy, Daegu Catholic University, 13-13 Hayang-ro, Hayang-eup, Gyeongsan, Gyeongbuk 38430, Republic of KoreaQurient Co., Ltd., C-dong-801, PDC, 242, Pangyo-ro, Bundang-gu, Seongnam, Gyeonggi 13487, Republic of KoreaQurient Co., Ltd., C-dong-801, PDC, 242, Pangyo-ro, Bundang-gu, Seongnam, Gyeonggi 13487, Republic of KoreaSchool of Pharmacy, Sungkyunkwan University, 2066 Seobu-ro, Jangan-gu, Suwon, Gyeonggi 16419, Republic of Korea; Corresponding authors.College of Pharmacy, Wonkwang University, 460 Iksan-daero, Iksan, Jeonbuk 54538, Republic of Korea; Corresponding authors.Telacebec is a new anti-tuberculosis agent with promising therapeutic activity and a favorable safety profile. This study aimed to characterize the pharmacokinetics of telacebec via interspecies scaling and population pharmacokinetic modeling for the prediction of human pharmacokinetics. Preclinical pharmacokinetic data were obtained from mice, rats, and dogs following intravenous and oral doses of telacebec. A population pharmacokinetic model was developed to describe the pharmacokinetic data from all three species. The disposition parameters were well correlated with the body weight for all species using an allometric equation. Thus, the allometric scaling was incorporated into the population pharmacokinetic model, which could simultaneously describe the plasma concentration vs. time data from all preclinical studies as well as the Phase 1A clinical study. The developed model was used to predict the pharmacokinetics of telacebec after IV injection, including the clearance (CL) of 168.58 [118.86 – 238.73] mL/min and volume of distribution (Vss) of 968.84 [396.87 – 2831.31] L for 80-kg human. The absolute bioavailability of telacebec in humans in the fed state was estimated as 70.34 ± 9.91%. Finally, the population pharmacokinetic model with allometric scaling was utilized to simulate the plasma concentration vs. time profiles of telacebec after multiple oral doses in humans. The model-predicted profiles well agreed with the observed data in Phase 1B clinical trial. The present pharmacokinetic model may help better understand the activity of telacebec, leading to the design of optimal dosing regimens and new formulation development.http://www.sciencedirect.com/science/article/pii/S0753332223012398TelacebecTuberculosisPharmacokineticsInterspecies scalingPopulation pharmacokinetic model |
| spellingShingle | Jeongjun Kim Tae Hwan Kim Jinho Choi Kiyean Nam Beom Soo Shin Soyoung Shin Novel modeling approach integrating population pharmacokinetics and interspecies scaling to predict human pharmacokinetics of the new anti-tuberculosis agent telacebec (Q203) Biomedicine & Pharmacotherapy Telacebec Tuberculosis Pharmacokinetics Interspecies scaling Population pharmacokinetic model |
| title | Novel modeling approach integrating population pharmacokinetics and interspecies scaling to predict human pharmacokinetics of the new anti-tuberculosis agent telacebec (Q203) |
| title_full | Novel modeling approach integrating population pharmacokinetics and interspecies scaling to predict human pharmacokinetics of the new anti-tuberculosis agent telacebec (Q203) |
| title_fullStr | Novel modeling approach integrating population pharmacokinetics and interspecies scaling to predict human pharmacokinetics of the new anti-tuberculosis agent telacebec (Q203) |
| title_full_unstemmed | Novel modeling approach integrating population pharmacokinetics and interspecies scaling to predict human pharmacokinetics of the new anti-tuberculosis agent telacebec (Q203) |
| title_short | Novel modeling approach integrating population pharmacokinetics and interspecies scaling to predict human pharmacokinetics of the new anti-tuberculosis agent telacebec (Q203) |
| title_sort | novel modeling approach integrating population pharmacokinetics and interspecies scaling to predict human pharmacokinetics of the new anti tuberculosis agent telacebec q203 |
| topic | Telacebec Tuberculosis Pharmacokinetics Interspecies scaling Population pharmacokinetic model |
| url | http://www.sciencedirect.com/science/article/pii/S0753332223012398 |
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