An In Silico Approach toward the Appropriate Absorption Rate Metric in Bioequivalence
In bioequivalence, the maximum plasma concentration (Cmax) is traditionally used as a metric for the absorption rate, despite the fact that there are several concerns. The idea of “average slope” (AS) was recently introduced as an alternative metric to reflect absorption rate. This study aims to fur...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-05-01
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| Series: | Pharmaceuticals |
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| Online Access: | https://www.mdpi.com/1424-8247/16/5/725 |
| _version_ | 1797598652736208896 |
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| author | Vangelis D. Karalis |
| author_facet | Vangelis D. Karalis |
| author_sort | Vangelis D. Karalis |
| collection | DOAJ |
| description | In bioequivalence, the maximum plasma concentration (Cmax) is traditionally used as a metric for the absorption rate, despite the fact that there are several concerns. The idea of “average slope” (AS) was recently introduced as an alternative metric to reflect absorption rate. This study aims to further extend the previous findings and apply an in silico approach to investigate the kinetic sensitivity of AS and Cmax. This computational analysis was applied to the C-t data of hydrochlorothiazide, donepezil, and amlodipine, which exhibit different absorption kinetics. Principal component analysis (PCA) was applied to uncover the relationships between all bioequivalence metrics. Monte Carlo simulations of bioequivalence trials were performed to investigate sensitivity. The appropriate programming codes were written in Python for the PCA and in MATLAB<sup>®</sup> for the simulations. The PCA verified the desired properties of AS and the unsuitability of Cmax to reflect absorption rate. The Monte Carlo simulations showed that AS is quite sensitive to detecting differences in absorption rate, while Cmax has almost negligible sensitivity. Cmax fails to reflect absorption rate, and its use in bioequivalence gives only a false impression. AS has the appropriate units, is easily calculated, exhibits high sensitivity, and has the desired properties of absorption rate. |
| first_indexed | 2024-03-11T03:25:12Z |
| format | Article |
| id | doaj.art-2cd8fac3328f4485822e2ade23c3ebcd |
| institution | Directory Open Access Journal |
| issn | 1424-8247 |
| language | English |
| last_indexed | 2024-03-11T03:25:12Z |
| publishDate | 2023-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceuticals |
| spelling | doaj.art-2cd8fac3328f4485822e2ade23c3ebcd2023-11-18T02:49:01ZengMDPI AGPharmaceuticals1424-82472023-05-0116572510.3390/ph16050725An In Silico Approach toward the Appropriate Absorption Rate Metric in BioequivalenceVangelis D. Karalis0Department of Pharmacy, School of Health Sciences, National and Kapodistrian University of Athens, 15784 Athens, GreeceIn bioequivalence, the maximum plasma concentration (Cmax) is traditionally used as a metric for the absorption rate, despite the fact that there are several concerns. The idea of “average slope” (AS) was recently introduced as an alternative metric to reflect absorption rate. This study aims to further extend the previous findings and apply an in silico approach to investigate the kinetic sensitivity of AS and Cmax. This computational analysis was applied to the C-t data of hydrochlorothiazide, donepezil, and amlodipine, which exhibit different absorption kinetics. Principal component analysis (PCA) was applied to uncover the relationships between all bioequivalence metrics. Monte Carlo simulations of bioequivalence trials were performed to investigate sensitivity. The appropriate programming codes were written in Python for the PCA and in MATLAB<sup>®</sup> for the simulations. The PCA verified the desired properties of AS and the unsuitability of Cmax to reflect absorption rate. The Monte Carlo simulations showed that AS is quite sensitive to detecting differences in absorption rate, while Cmax has almost negligible sensitivity. Cmax fails to reflect absorption rate, and its use in bioequivalence gives only a false impression. AS has the appropriate units, is easily calculated, exhibits high sensitivity, and has the desired properties of absorption rate.https://www.mdpi.com/1424-8247/16/5/725in silico methodsbioequivalencepharmacokineticsabsorption ratemachine learningMonte Carlo simulations |
| spellingShingle | Vangelis D. Karalis An In Silico Approach toward the Appropriate Absorption Rate Metric in Bioequivalence Pharmaceuticals in silico methods bioequivalence pharmacokinetics absorption rate machine learning Monte Carlo simulations |
| title | An In Silico Approach toward the Appropriate Absorption Rate Metric in Bioequivalence |
| title_full | An In Silico Approach toward the Appropriate Absorption Rate Metric in Bioequivalence |
| title_fullStr | An In Silico Approach toward the Appropriate Absorption Rate Metric in Bioequivalence |
| title_full_unstemmed | An In Silico Approach toward the Appropriate Absorption Rate Metric in Bioequivalence |
| title_short | An In Silico Approach toward the Appropriate Absorption Rate Metric in Bioequivalence |
| title_sort | in silico approach toward the appropriate absorption rate metric in bioequivalence |
| topic | in silico methods bioequivalence pharmacokinetics absorption rate machine learning Monte Carlo simulations |
| url | https://www.mdpi.com/1424-8247/16/5/725 |
| work_keys_str_mv | AT vangelisdkaralis aninsilicoapproachtowardtheappropriateabsorptionratemetricinbioequivalence AT vangelisdkaralis insilicoapproachtowardtheappropriateabsorptionratemetricinbioequivalence |