Preclinical Bioavailability Assessment of a Poorly Water-Soluble Drug, HGR4113, Using a Stable Isotope Tracer
Drug solubility limits intravenous dosing for poorly water-soluble medicines, which misrepresents their bioavailability estimation. The current study explored a method using a stable isotope tracer to assess the bioavailability of drugs that are poorly water-soluble. HGR4113 and its deuterated analo...
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| Format: | Article |
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MDPI AG
2023-06-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/15/6/1684 |
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| author | Eun Ji Ha Jeong In Seo Shaheed Ur Rehman Hyung Soon Park Sang-Ku Yoo Hye Hyun Yoo |
| author_facet | Eun Ji Ha Jeong In Seo Shaheed Ur Rehman Hyung Soon Park Sang-Ku Yoo Hye Hyun Yoo |
| author_sort | Eun Ji Ha |
| collection | DOAJ |
| description | Drug solubility limits intravenous dosing for poorly water-soluble medicines, which misrepresents their bioavailability estimation. The current study explored a method using a stable isotope tracer to assess the bioavailability of drugs that are poorly water-soluble. HGR4113 and its deuterated analog, HGR4113-d7, were tested as model drugs. To determine the level of HGR4113 and HGR4113-d7 in rat plasma, a bioanalytical method using LC-MS/MS was developed. The HGR4113-d7 was intravenously administered to rats that were orally pre-administered HGR4113 at different doses; subsequently, the plasma samples were collected. HGR4113 and HGR4113-d7 were simultaneously determined in the plasma samples, and bioavailability was calculated using plasma drug concentration values. The bioavailability of HGR4113 was 53.3% ± 19.5%, 56.9% ± 14.0%, and 67.8% ± 16.7% after oral dosages of 40, 80, and 160 mg/kg, respectively. By eliminating the differences in clearance between intravenous and oral dosages at different levels, acquired data showed that the current method reduced measurement errors in bioavailability when compared to the conventional approach. The present study suggests a prominent method for evaluating the bioavailability of drugs with poor aqueous solubility in preclinical studies. |
| first_indexed | 2024-03-11T02:03:13Z |
| format | Article |
| id | doaj.art-6f943bef518e4e6ebae61a5fd0e2d7fc |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-11T02:03:13Z |
| publishDate | 2023-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-6f943bef518e4e6ebae61a5fd0e2d7fc2023-11-18T12:05:00ZengMDPI AGPharmaceutics1999-49232023-06-01156168410.3390/pharmaceutics15061684Preclinical Bioavailability Assessment of a Poorly Water-Soluble Drug, HGR4113, Using a Stable Isotope TracerEun Ji Ha0Jeong In Seo1Shaheed Ur Rehman2Hyung Soon Park3Sang-Ku Yoo4Hye Hyun Yoo5Institute of Pharmaceutical Science and Technology, College of Pharmacy, Hanyang University, Ansan 15588, Gyeonggi-do, Republic of KoreaInstitute of Pharmaceutical Science and Technology, College of Pharmacy, Hanyang University, Ansan 15588, Gyeonggi-do, Republic of KoreaDepartment of Pharmacy, Abasyn University, Peshawar 25000, PakistanGlaceum Inc., Yeongtong-gu, Suwon 16675, Gyeonggi-do, Republic of KoreaGlaceum Inc., Yeongtong-gu, Suwon 16675, Gyeonggi-do, Republic of KoreaInstitute of Pharmaceutical Science and Technology, College of Pharmacy, Hanyang University, Ansan 15588, Gyeonggi-do, Republic of KoreaDrug solubility limits intravenous dosing for poorly water-soluble medicines, which misrepresents their bioavailability estimation. The current study explored a method using a stable isotope tracer to assess the bioavailability of drugs that are poorly water-soluble. HGR4113 and its deuterated analog, HGR4113-d7, were tested as model drugs. To determine the level of HGR4113 and HGR4113-d7 in rat plasma, a bioanalytical method using LC-MS/MS was developed. The HGR4113-d7 was intravenously administered to rats that were orally pre-administered HGR4113 at different doses; subsequently, the plasma samples were collected. HGR4113 and HGR4113-d7 were simultaneously determined in the plasma samples, and bioavailability was calculated using plasma drug concentration values. The bioavailability of HGR4113 was 53.3% ± 19.5%, 56.9% ± 14.0%, and 67.8% ± 16.7% after oral dosages of 40, 80, and 160 mg/kg, respectively. By eliminating the differences in clearance between intravenous and oral dosages at different levels, acquired data showed that the current method reduced measurement errors in bioavailability when compared to the conventional approach. The present study suggests a prominent method for evaluating the bioavailability of drugs with poor aqueous solubility in preclinical studies.https://www.mdpi.com/1999-4923/15/6/1684bioavailabilitystable isotopepoorly water-soluble drugsliquid chromatography–tandem mass spectrometry |
| spellingShingle | Eun Ji Ha Jeong In Seo Shaheed Ur Rehman Hyung Soon Park Sang-Ku Yoo Hye Hyun Yoo Preclinical Bioavailability Assessment of a Poorly Water-Soluble Drug, HGR4113, Using a Stable Isotope Tracer Pharmaceutics bioavailability stable isotope poorly water-soluble drugs liquid chromatography–tandem mass spectrometry |
| title | Preclinical Bioavailability Assessment of a Poorly Water-Soluble Drug, HGR4113, Using a Stable Isotope Tracer |
| title_full | Preclinical Bioavailability Assessment of a Poorly Water-Soluble Drug, HGR4113, Using a Stable Isotope Tracer |
| title_fullStr | Preclinical Bioavailability Assessment of a Poorly Water-Soluble Drug, HGR4113, Using a Stable Isotope Tracer |
| title_full_unstemmed | Preclinical Bioavailability Assessment of a Poorly Water-Soluble Drug, HGR4113, Using a Stable Isotope Tracer |
| title_short | Preclinical Bioavailability Assessment of a Poorly Water-Soluble Drug, HGR4113, Using a Stable Isotope Tracer |
| title_sort | preclinical bioavailability assessment of a poorly water soluble drug hgr4113 using a stable isotope tracer |
| topic | bioavailability stable isotope poorly water-soluble drugs liquid chromatography–tandem mass spectrometry |
| url | https://www.mdpi.com/1999-4923/15/6/1684 |
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