A novel method to estimate the absorption rate constant for two-compartment model fitted drugs without intravenous pharmacokinetic data
The in vivo performances of most drugs after extravascular administration are fitted well with the two-compartment pharmacokinetic (PK) model, but the estimation of absorption rate constant (ka) for these drugs becomes difficult during unavailability of intravenous PK data. Herein, we developed a no...
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| Format: | Article |
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Frontiers Media S.A.
2023-05-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2023.1087913/full |
| _version_ | 1797833595823325184 |
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| author | Fan Liu Fan Liu Hanxi Yi Lei Wang Lei Wang Lei Wang Zeneng Cheng Guoqing Zhang |
| author_facet | Fan Liu Fan Liu Hanxi Yi Lei Wang Lei Wang Lei Wang Zeneng Cheng Guoqing Zhang |
| author_sort | Fan Liu |
| collection | DOAJ |
| description | The in vivo performances of most drugs after extravascular administration are fitted well with the two-compartment pharmacokinetic (PK) model, but the estimation of absorption rate constant (ka) for these drugs becomes difficult during unavailability of intravenous PK data. Herein, we developed a novel method, called the direct method, for estimating the ka values of drugs without using intravenous PK data, by proposing a new PK parameter, namely, maximum apparent rate constant of disposition (kmax). The accuracy of the direct method in ka estimation was determined using the setting parameters (k12, k21, and k10 values at high, medium, and low levels, respectively) and clinical data. The results showed that the absolute relative error of ka estimated using the direct method was significantly lower than that obtained using both the Loo-Riegelman method and the statistical moment method for the setting parameters. Human PK studies of telmisartan, candesartan cilexetil, and tenofovir disoproxil fumarate indicated that the ka values of these drugs were accurately estimated using the direct method based on good correlations between the ka values and other PK parameters that reflected the absorption properties of drugs in vivo (Tmax, Cmax, and Cmax/AUC0-t). This novel method can be applied in situations where intravenous PK data cannot be obtained and is expected to provide valuable support for PK evaluation and in vitro-in vivo correlation establishment. |
| first_indexed | 2024-04-09T14:26:44Z |
| format | Article |
| id | doaj.art-00cf11f7a61b40e9b99523adc21f9544 |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-04-09T14:26:44Z |
| publishDate | 2023-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-00cf11f7a61b40e9b99523adc21f95442023-05-04T04:11:55ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122023-05-011410.3389/fphar.2023.10879131087913A novel method to estimate the absorption rate constant for two-compartment model fitted drugs without intravenous pharmacokinetic dataFan Liu0Fan Liu1Hanxi Yi2Lei Wang3Lei Wang4Lei Wang5Zeneng Cheng6Guoqing Zhang7Xiangya School of Pharmaceutical Sciences, Central South University, Changsha, Hunan, ChinaDepartment of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan, ChinaSchool of Basic Medicine, Central South University, Changsha, Hunan, ChinaXiangya School of Pharmaceutical Sciences, Central South University, Changsha, Hunan, ChinaDepartment of Rheumatology and Immunology, The Second Clinical Medical College, Jinan University (Shenzhen People's Hospital), Shenzhen, ChinaIntegrated Chinese and Western Medicine Postdoctoral Research Station, Jinan University, Guangzhou, ChinaXiangya School of Pharmaceutical Sciences, Central South University, Changsha, Hunan, ChinaXiangya School of Pharmaceutical Sciences, Central South University, Changsha, Hunan, ChinaThe in vivo performances of most drugs after extravascular administration are fitted well with the two-compartment pharmacokinetic (PK) model, but the estimation of absorption rate constant (ka) for these drugs becomes difficult during unavailability of intravenous PK data. Herein, we developed a novel method, called the direct method, for estimating the ka values of drugs without using intravenous PK data, by proposing a new PK parameter, namely, maximum apparent rate constant of disposition (kmax). The accuracy of the direct method in ka estimation was determined using the setting parameters (k12, k21, and k10 values at high, medium, and low levels, respectively) and clinical data. The results showed that the absolute relative error of ka estimated using the direct method was significantly lower than that obtained using both the Loo-Riegelman method and the statistical moment method for the setting parameters. Human PK studies of telmisartan, candesartan cilexetil, and tenofovir disoproxil fumarate indicated that the ka values of these drugs were accurately estimated using the direct method based on good correlations between the ka values and other PK parameters that reflected the absorption properties of drugs in vivo (Tmax, Cmax, and Cmax/AUC0-t). This novel method can be applied in situations where intravenous PK data cannot be obtained and is expected to provide valuable support for PK evaluation and in vitro-in vivo correlation establishment.https://www.frontiersin.org/articles/10.3389/fphar.2023.1087913/fullabsorption rate constantthe direct methodmaximum apparent rate constant of dispositiontwo-compartment modelextravascular administration |
| spellingShingle | Fan Liu Fan Liu Hanxi Yi Lei Wang Lei Wang Lei Wang Zeneng Cheng Guoqing Zhang A novel method to estimate the absorption rate constant for two-compartment model fitted drugs without intravenous pharmacokinetic data Frontiers in Pharmacology absorption rate constant the direct method maximum apparent rate constant of disposition two-compartment model extravascular administration |
| title | A novel method to estimate the absorption rate constant for two-compartment model fitted drugs without intravenous pharmacokinetic data |
| title_full | A novel method to estimate the absorption rate constant for two-compartment model fitted drugs without intravenous pharmacokinetic data |
| title_fullStr | A novel method to estimate the absorption rate constant for two-compartment model fitted drugs without intravenous pharmacokinetic data |
| title_full_unstemmed | A novel method to estimate the absorption rate constant for two-compartment model fitted drugs without intravenous pharmacokinetic data |
| title_short | A novel method to estimate the absorption rate constant for two-compartment model fitted drugs without intravenous pharmacokinetic data |
| title_sort | novel method to estimate the absorption rate constant for two compartment model fitted drugs without intravenous pharmacokinetic data |
| topic | absorption rate constant the direct method maximum apparent rate constant of disposition two-compartment model extravascular administration |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2023.1087913/full |
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