Pharmacokinetics, Safety and Pharmacokinetics/Pharmacodynamics Analysis of Omadacycline in Chinese Healthy Subjects
Objective: Omadacycline is a new type of aminomethylcycline antibiotic, having a broad antibacterial spectrum. But the pharmacokinetic characteristics and safety profile of the Chinese population remain unknown. It is also unclear whether the US-approved treatment regimen is applicable for the Chine...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-04-01
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| Series: | Frontiers in Pharmacology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2022.869237/full |
| _version_ | 1818025390903394304 |
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| author | Haijing Yang Haijing Yang Haijing Yang Zhiwei Huang Zhiwei Huang Zhiwei Huang Yuancheng Chen Yuancheng Chen Yuancheng Chen Yusong Zhu Guoying Cao Guoying Cao Guoying Cao Jingjing Wang Jingjing Wang Jingjing Wang Yan Guo Yan Guo Yan Guo Jicheng Yu Jicheng Yu Jicheng Yu Jufang Wu Jufang Wu Jufang Wu Lichuan Liu Jun Deng Jing Liu Harald Reinhart Jing Zhang Jing Zhang Jing Zhang Xiaojie Wu Xiaojie Wu Xiaojie Wu |
| author_facet | Haijing Yang Haijing Yang Haijing Yang Zhiwei Huang Zhiwei Huang Zhiwei Huang Yuancheng Chen Yuancheng Chen Yuancheng Chen Yusong Zhu Guoying Cao Guoying Cao Guoying Cao Jingjing Wang Jingjing Wang Jingjing Wang Yan Guo Yan Guo Yan Guo Jicheng Yu Jicheng Yu Jicheng Yu Jufang Wu Jufang Wu Jufang Wu Lichuan Liu Jun Deng Jing Liu Harald Reinhart Jing Zhang Jing Zhang Jing Zhang Xiaojie Wu Xiaojie Wu Xiaojie Wu |
| author_sort | Haijing Yang |
| collection | DOAJ |
| description | Objective: Omadacycline is a new type of aminomethylcycline antibiotic, having a broad antibacterial spectrum. But the pharmacokinetic characteristics and safety profile of the Chinese population remain unknown. It is also unclear whether the US-approved treatment regimen is applicable for the Chinese population.Methods: In a randomized, double-blinded, placebo-controlled dose-escalated trial, the pharmacokinetics of omadacycline was evaluated by a non-compartmental and compartmental model. Monte Carlo simulations were performed using the pharmacokinetic data from the Chinese population to evaluate the probability of target attainment (PTA) and the cumulative fraction of response (CFR) of the US FDA-approved dose regimen.Results: The three-compartment model successfully described the rapid distribution and slow elimination of omadacycline after the intravenous infusion (i.v.). The double-peak concentration-time curve of the oral absorption (p.o.) was explained by the two-compartment model with two absorption compartments. The steady-state AUC of 100 mg omadacycline i.v. and 300 mg omadacycline p. o. were 12.1 and 19.4 mg h/L, respectively. Pharmacokinetics/pharmacodynamics (PK/PD) analysis showed that the omadacycline dosing regimen with a loading dose (200 mg i.v. q24 h, 100 mg i.v. q12 h, 450 mg p. o. q24 h × 2 days or 300 mg p. o. q12 h) and maintenance dose (100 mg i.v. q24 h or 300 mg p. o. q24 h) could cover the main pathogens of the indications acute bacterial skin and skin structure infections (ABSSSI) and community-acquired bacterial pneumonia (CABP): Staphylococcus aureus and Streptococcus pneumoniae. Also, omadacycline had showed a good safety profile in the Chinese population.Conclusions: With the evidence provided, omadacycline could be a novel treatment option to Chinese patients with ABSSSI and CABP. |
| first_indexed | 2024-12-10T04:15:21Z |
| format | Article |
| id | doaj.art-835c36f73093449cb301f7112048faf0 |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-12-10T04:15:21Z |
| publishDate | 2022-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-835c36f73093449cb301f7112048faf02022-12-22T02:02:37ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122022-04-011310.3389/fphar.2022.869237869237Pharmacokinetics, Safety and Pharmacokinetics/Pharmacodynamics Analysis of Omadacycline in Chinese Healthy SubjectsHaijing Yang0Haijing Yang1Haijing Yang2Zhiwei Huang3Zhiwei Huang4Zhiwei Huang5Yuancheng Chen6Yuancheng Chen7Yuancheng Chen8Yusong Zhu9Guoying Cao10Guoying Cao11Guoying Cao12Jingjing Wang13Jingjing Wang14Jingjing Wang15Yan Guo16Yan Guo17Yan Guo18Jicheng Yu19Jicheng Yu20Jicheng Yu21Jufang Wu22Jufang Wu23Jufang Wu24Lichuan Liu25Jun Deng26Jing Liu27Harald Reinhart28Jing Zhang29Jing Zhang30Jing Zhang31Xiaojie Wu32Xiaojie Wu33Xiaojie Wu34Phase I Clinical Research Center, Huashan Hospital, Fudan University, Shanghai, ChinaKey Laboratory of Clinical Pharmacology of Antibiotics, National Health Commission, Shanghai, ChinaNational Clinical Research Center for Geriatric Diseases (Huashan Hospital), Shanghai, ChinaKey Laboratory of Clinical Pharmacology of Antibiotics, National Health Commission, Shanghai, ChinaNational Clinical Research Center for Geriatric Diseases (Huashan Hospital), Shanghai, ChinaInstitute of Antibiotics, Huashan Hospital, Fudan University, Shanghai, ChinaPhase I Clinical Research Center, Huashan Hospital, Fudan University, Shanghai, ChinaKey Laboratory of Clinical Pharmacology of Antibiotics, National Health Commission, Shanghai, ChinaNational Clinical Research Center for Geriatric Diseases (Huashan Hospital), Shanghai, ChinaZai Lab (Shanghai) Co., Ltd., Shanghai, ChinaPhase I Clinical Research Center, Huashan Hospital, Fudan University, Shanghai, ChinaKey Laboratory of Clinical Pharmacology of Antibiotics, National Health Commission, Shanghai, ChinaNational Clinical Research Center for Geriatric Diseases (Huashan Hospital), Shanghai, ChinaPhase I Clinical Research Center, Huashan Hospital, Fudan University, Shanghai, ChinaKey Laboratory of Clinical Pharmacology of Antibiotics, National Health Commission, Shanghai, ChinaNational Clinical Research Center for Geriatric Diseases (Huashan Hospital), Shanghai, ChinaKey Laboratory of Clinical Pharmacology of Antibiotics, National Health Commission, Shanghai, ChinaNational Clinical Research Center for Geriatric Diseases (Huashan Hospital), Shanghai, ChinaInstitute of Antibiotics, Huashan Hospital, Fudan University, Shanghai, ChinaPhase I Clinical Research Center, Huashan Hospital, Fudan University, Shanghai, ChinaKey Laboratory of Clinical Pharmacology of Antibiotics, National Health Commission, Shanghai, ChinaNational Clinical Research Center for Geriatric Diseases (Huashan Hospital), Shanghai, ChinaPhase I Clinical Research Center, Huashan Hospital, Fudan University, Shanghai, ChinaKey Laboratory of Clinical Pharmacology of Antibiotics, National Health Commission, Shanghai, ChinaNational Clinical Research Center for Geriatric Diseases (Huashan Hospital), Shanghai, ChinaZai Lab (Shanghai) Co., Ltd., Shanghai, ChinaZai Lab (Shanghai) Co., Ltd., Shanghai, ChinaZai Lab (Shanghai) Co., Ltd., Shanghai, ChinaZai Lab (Shanghai) Co., Ltd., Shanghai, ChinaKey Laboratory of Clinical Pharmacology of Antibiotics, National Health Commission, Shanghai, ChinaNational Clinical Research Center for Geriatric Diseases (Huashan Hospital), Shanghai, ChinaInstitute of Antibiotics, Huashan Hospital, Fudan University, Shanghai, ChinaPhase I Clinical Research Center, Huashan Hospital, Fudan University, Shanghai, ChinaKey Laboratory of Clinical Pharmacology of Antibiotics, National Health Commission, Shanghai, ChinaNational Clinical Research Center for Geriatric Diseases (Huashan Hospital), Shanghai, ChinaObjective: Omadacycline is a new type of aminomethylcycline antibiotic, having a broad antibacterial spectrum. But the pharmacokinetic characteristics and safety profile of the Chinese population remain unknown. It is also unclear whether the US-approved treatment regimen is applicable for the Chinese population.Methods: In a randomized, double-blinded, placebo-controlled dose-escalated trial, the pharmacokinetics of omadacycline was evaluated by a non-compartmental and compartmental model. Monte Carlo simulations were performed using the pharmacokinetic data from the Chinese population to evaluate the probability of target attainment (PTA) and the cumulative fraction of response (CFR) of the US FDA-approved dose regimen.Results: The three-compartment model successfully described the rapid distribution and slow elimination of omadacycline after the intravenous infusion (i.v.). The double-peak concentration-time curve of the oral absorption (p.o.) was explained by the two-compartment model with two absorption compartments. The steady-state AUC of 100 mg omadacycline i.v. and 300 mg omadacycline p. o. were 12.1 and 19.4 mg h/L, respectively. Pharmacokinetics/pharmacodynamics (PK/PD) analysis showed that the omadacycline dosing regimen with a loading dose (200 mg i.v. q24 h, 100 mg i.v. q12 h, 450 mg p. o. q24 h × 2 days or 300 mg p. o. q12 h) and maintenance dose (100 mg i.v. q24 h or 300 mg p. o. q24 h) could cover the main pathogens of the indications acute bacterial skin and skin structure infections (ABSSSI) and community-acquired bacterial pneumonia (CABP): Staphylococcus aureus and Streptococcus pneumoniae. Also, omadacycline had showed a good safety profile in the Chinese population.Conclusions: With the evidence provided, omadacycline could be a novel treatment option to Chinese patients with ABSSSI and CABP.https://www.frontiersin.org/articles/10.3389/fphar.2022.869237/fulldouble-peak absorptioncompartment modelMonte Carlo simulationmethicillin-resistant Staphylococcus aureusacute bacterial skin and skin structure infectionscommunity-acquired bacterial pneumonia |
| spellingShingle | Haijing Yang Haijing Yang Haijing Yang Zhiwei Huang Zhiwei Huang Zhiwei Huang Yuancheng Chen Yuancheng Chen Yuancheng Chen Yusong Zhu Guoying Cao Guoying Cao Guoying Cao Jingjing Wang Jingjing Wang Jingjing Wang Yan Guo Yan Guo Yan Guo Jicheng Yu Jicheng Yu Jicheng Yu Jufang Wu Jufang Wu Jufang Wu Lichuan Liu Jun Deng Jing Liu Harald Reinhart Jing Zhang Jing Zhang Jing Zhang Xiaojie Wu Xiaojie Wu Xiaojie Wu Pharmacokinetics, Safety and Pharmacokinetics/Pharmacodynamics Analysis of Omadacycline in Chinese Healthy Subjects Frontiers in Pharmacology double-peak absorption compartment model Monte Carlo simulation methicillin-resistant Staphylococcus aureus acute bacterial skin and skin structure infections community-acquired bacterial pneumonia |
| title | Pharmacokinetics, Safety and Pharmacokinetics/Pharmacodynamics Analysis of Omadacycline in Chinese Healthy Subjects |
| title_full | Pharmacokinetics, Safety and Pharmacokinetics/Pharmacodynamics Analysis of Omadacycline in Chinese Healthy Subjects |
| title_fullStr | Pharmacokinetics, Safety and Pharmacokinetics/Pharmacodynamics Analysis of Omadacycline in Chinese Healthy Subjects |
| title_full_unstemmed | Pharmacokinetics, Safety and Pharmacokinetics/Pharmacodynamics Analysis of Omadacycline in Chinese Healthy Subjects |
| title_short | Pharmacokinetics, Safety and Pharmacokinetics/Pharmacodynamics Analysis of Omadacycline in Chinese Healthy Subjects |
| title_sort | pharmacokinetics safety and pharmacokinetics pharmacodynamics analysis of omadacycline in chinese healthy subjects |
| topic | double-peak absorption compartment model Monte Carlo simulation methicillin-resistant Staphylococcus aureus acute bacterial skin and skin structure infections community-acquired bacterial pneumonia |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2022.869237/full |
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