Pharmacokinetics of Jaspine B and Enhancement of Intestinal Absorption of Jaspine B in the Presence of Bile Acid in Rats
We aimed to investigate the pharmacokinetics and the underlying mechanisms of the intestinal absorption, distribution, metabolism, and excretion of Jaspine B in rats. The oral bioavailability of Jaspine B was 6.2%, but it decreased to 1.6% in bile-depleted rats and increased to 41.2% (normal) and 23...
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MDPI AG
2017-09-01
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| Series: | Marine Drugs |
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| Online Access: | https://www.mdpi.com/1660-3397/15/9/279 |
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| author | Min-Koo Choi Jihoon Lee So Jeong Nam Yun Ju Kang Youjin Han Kwangik Choi Young A. Choi Mihwa Kwon Dongjoo Lee Im-Sook Song |
| author_facet | Min-Koo Choi Jihoon Lee So Jeong Nam Yun Ju Kang Youjin Han Kwangik Choi Young A. Choi Mihwa Kwon Dongjoo Lee Im-Sook Song |
| author_sort | Min-Koo Choi |
| collection | DOAJ |
| description | We aimed to investigate the pharmacokinetics and the underlying mechanisms of the intestinal absorption, distribution, metabolism, and excretion of Jaspine B in rats. The oral bioavailability of Jaspine B was 6.2%, but it decreased to 1.6% in bile-depleted rats and increased to 41.2% (normal) and 23.5% (bile-depleted) with taurocholate supplementation (60 mg/kg). Consistent with the increased absorption in the presence of bile salts, rat intestinal permeability of Jaspine B also increased in the presence of 10 mM taurocholate or 20% bile. Further studies demonstrated that the enhanced intestinal permeability with bile salts was due to increased lipophilicity and decreased membrane integrity. Jaspine B was designated as a highly tissue-distributed compound, because it showed large tissue to plasma ratios in the brain, kidney, heart, and spleen. Moreover, the recovery of Jaspine B from the feces and urine after an intravenous administration was about 6.3%, suggesting a substantial metabolism of Jaspine B. Consistent with this observation, 80% of the administered Jaspine B was degraded after 1 h incubation with rat liver microsomes. In conclusion, the facilitated intestinal permeability in the presence of bile salts could significantly increase the bioavailability of Jaspine B and could lead to the development of oral formulations of Jaspine B with bile salts. Moreover, the highly distributed features of Jaspine B in the brain, kidney, heart, and spleen should be carefully considered in the therapeutic effect and toxicity of this compound. |
| first_indexed | 2024-04-14T05:29:06Z |
| format | Article |
| id | doaj.art-5a86dac584ad4c04a44f77da7712e202 |
| institution | Directory Open Access Journal |
| issn | 1660-3397 |
| language | English |
| last_indexed | 2024-04-14T05:29:06Z |
| publishDate | 2017-09-01 |
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| record_format | Article |
| series | Marine Drugs |
| spelling | doaj.art-5a86dac584ad4c04a44f77da7712e2022022-12-22T02:09:52ZengMDPI AGMarine Drugs1660-33972017-09-0115927910.3390/md15090279md15090279Pharmacokinetics of Jaspine B and Enhancement of Intestinal Absorption of Jaspine B in the Presence of Bile Acid in RatsMin-Koo Choi0Jihoon Lee1So Jeong Nam2Yun Ju Kang3Youjin Han4Kwangik Choi5Young A. Choi6Mihwa Kwon7Dongjoo Lee8Im-Sook Song9College of Pharmacy, Dankook University, Cheon-an 31116, KoreaCollege of Pharmacy and Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu 41566, KoreaCollege of Pharmacy and Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu 41566, KoreaCollege of Pharmacy and Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu 41566, KoreaCollege of Pharmacy and Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu 41566, KoreaCollege of Pharmacy and Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu 41566, KoreaCollege of Pharmacy, Dankook University, Cheon-an 31116, KoreaCollege of Pharmacy and Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu 41566, KoreaCollege of Pharmacy, Ajou University, Suwon 16499, KoreaCollege of Pharmacy and Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu 41566, KoreaWe aimed to investigate the pharmacokinetics and the underlying mechanisms of the intestinal absorption, distribution, metabolism, and excretion of Jaspine B in rats. The oral bioavailability of Jaspine B was 6.2%, but it decreased to 1.6% in bile-depleted rats and increased to 41.2% (normal) and 23.5% (bile-depleted) with taurocholate supplementation (60 mg/kg). Consistent with the increased absorption in the presence of bile salts, rat intestinal permeability of Jaspine B also increased in the presence of 10 mM taurocholate or 20% bile. Further studies demonstrated that the enhanced intestinal permeability with bile salts was due to increased lipophilicity and decreased membrane integrity. Jaspine B was designated as a highly tissue-distributed compound, because it showed large tissue to plasma ratios in the brain, kidney, heart, and spleen. Moreover, the recovery of Jaspine B from the feces and urine after an intravenous administration was about 6.3%, suggesting a substantial metabolism of Jaspine B. Consistent with this observation, 80% of the administered Jaspine B was degraded after 1 h incubation with rat liver microsomes. In conclusion, the facilitated intestinal permeability in the presence of bile salts could significantly increase the bioavailability of Jaspine B and could lead to the development of oral formulations of Jaspine B with bile salts. Moreover, the highly distributed features of Jaspine B in the brain, kidney, heart, and spleen should be carefully considered in the therapeutic effect and toxicity of this compound.https://www.mdpi.com/1660-3397/15/9/279Jaspine Bbile saltsintestinal permeabilitybioavailabilitymetabolic instability |
| spellingShingle | Min-Koo Choi Jihoon Lee So Jeong Nam Yun Ju Kang Youjin Han Kwangik Choi Young A. Choi Mihwa Kwon Dongjoo Lee Im-Sook Song Pharmacokinetics of Jaspine B and Enhancement of Intestinal Absorption of Jaspine B in the Presence of Bile Acid in Rats Marine Drugs Jaspine B bile salts intestinal permeability bioavailability metabolic instability |
| title | Pharmacokinetics of Jaspine B and Enhancement of Intestinal Absorption of Jaspine B in the Presence of Bile Acid in Rats |
| title_full | Pharmacokinetics of Jaspine B and Enhancement of Intestinal Absorption of Jaspine B in the Presence of Bile Acid in Rats |
| title_fullStr | Pharmacokinetics of Jaspine B and Enhancement of Intestinal Absorption of Jaspine B in the Presence of Bile Acid in Rats |
| title_full_unstemmed | Pharmacokinetics of Jaspine B and Enhancement of Intestinal Absorption of Jaspine B in the Presence of Bile Acid in Rats |
| title_short | Pharmacokinetics of Jaspine B and Enhancement of Intestinal Absorption of Jaspine B in the Presence of Bile Acid in Rats |
| title_sort | pharmacokinetics of jaspine b and enhancement of intestinal absorption of jaspine b in the presence of bile acid in rats |
| topic | Jaspine B bile salts intestinal permeability bioavailability metabolic instability |
| url | https://www.mdpi.com/1660-3397/15/9/279 |
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