Evaluation of Pharmacokinetic Feasibility of Febuxostat/L-pyroglutamic Acid Cocrystals in Rats and Mice
Febuxostat (FBX), a selective xanthine oxidase inhibitor, belongs to BCS class II, showing low solubility and high permeability with a moderate <i>F</i> value (<49%). Recently, FBX/L-pyroglutamic acid cocrystal (FBX-PG) was developed with an improving 4-fold increase of FBX solubility...
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MDPI AG
2023-08-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/15/8/2167 |
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| author | Jeong-Eun Yu Byoung Hoon You Mingoo Bae Seung Yon Han Kiwon Jung Young Hee Choi |
| author_facet | Jeong-Eun Yu Byoung Hoon You Mingoo Bae Seung Yon Han Kiwon Jung Young Hee Choi |
| author_sort | Jeong-Eun Yu |
| collection | DOAJ |
| description | Febuxostat (FBX), a selective xanthine oxidase inhibitor, belongs to BCS class II, showing low solubility and high permeability with a moderate <i>F</i> value (<49%). Recently, FBX/L-pyroglutamic acid cocrystal (FBX-PG) was developed with an improving 4-fold increase of FBX solubility. Nevertheless, the in vivo pharmacokinetic properties of FBX-PG have not been evaluated yet. Therefore, the pharmacokinetic feasibility of FBX in FBX- and FBX-PG-treated rats and mice was compared in this study. The results showed that the bioavailability (<i>F</i>) values of FBX were 210% and 159% in FBX-PG-treated rats and mice, respectively. The 2.10-fold greater total area under the plasma concentration–time curve from time zero to infinity (AUC<sub>0-inf</sub>) of FBX was due to the increased absorption [i.e., 2.60-fold higher the first peak plasma concentration (<i>C</i><sub>max,1</sub>) at 15 min] and entero-hepatic circulation of FBX [i.e., 1.68-fold higher the second peak plasma concentration (<i>C</i><sub>max,2</sub>) at 600 min] in FBX-PG-treated rats compared to the FBX-treated rats. The 1.59-fold greater AUC<sub>0-inf</sub> of FBX was due to a 1.65-fold higher <i>C</i><sub>max,1</sub> at 5 min, and a 1.15-fold higher <i>C</i><sub>max,2</sub> at 720 min of FBX in FBX-PG-treated mice compared to those in FBX-treated mice. FBX was highly distributed in the liver, stomach, small intestine, and lungs in both groups of mice, and the FBX distributions to the liver and lungs were increased in FBX-PG-treated mice compared to FBX-treated mice. The results suggest the FBX-PG has a suitable pharmacokinetic profile of FBX for improving its oral <i>F</i> value. |
| first_indexed | 2024-03-10T23:39:02Z |
| format | Article |
| id | doaj.art-dc425f5debcc449b8107e262e0c3f9ea |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-10T23:39:02Z |
| publishDate | 2023-08-01 |
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| series | Pharmaceutics |
| spelling | doaj.art-dc425f5debcc449b8107e262e0c3f9ea2023-11-19T02:37:55ZengMDPI AGPharmaceutics1999-49232023-08-01158216710.3390/pharmaceutics15082167Evaluation of Pharmacokinetic Feasibility of Febuxostat/L-pyroglutamic Acid Cocrystals in Rats and MiceJeong-Eun Yu0Byoung Hoon You1Mingoo Bae2Seung Yon Han3Kiwon Jung4Young Hee Choi5College of Pharmacy and Integrated Research Institute for Drug Development, Dongguk University_Seoul, 32 Dongguk-ro, Ilsandong-gu, Goyang-si 10326, Gyeonggi-do, Republic of KoreaCollege of Pharmacy and Integrated Research Institute for Drug Development, Dongguk University_Seoul, 32 Dongguk-ro, Ilsandong-gu, Goyang-si 10326, Gyeonggi-do, Republic of KoreaCollege of Pharmacy and Integrated Research Institute for Drug Development, Dongguk University_Seoul, 32 Dongguk-ro, Ilsandong-gu, Goyang-si 10326, Gyeonggi-do, Republic of KoreaCollege of Pharmacy and Integrated Research Institute for Drug Development, Dongguk University_Seoul, 32 Dongguk-ro, Ilsandong-gu, Goyang-si 10326, Gyeonggi-do, Republic of KoreaCollege of Pharmacy, CHA University, 335 Pangyo-ro, Bundang-gu, Seongnam-si 13488, Gyeonggi-do, Republic of KoreaCollege of Pharmacy and Integrated Research Institute for Drug Development, Dongguk University_Seoul, 32 Dongguk-ro, Ilsandong-gu, Goyang-si 10326, Gyeonggi-do, Republic of KoreaFebuxostat (FBX), a selective xanthine oxidase inhibitor, belongs to BCS class II, showing low solubility and high permeability with a moderate <i>F</i> value (<49%). Recently, FBX/L-pyroglutamic acid cocrystal (FBX-PG) was developed with an improving 4-fold increase of FBX solubility. Nevertheless, the in vivo pharmacokinetic properties of FBX-PG have not been evaluated yet. Therefore, the pharmacokinetic feasibility of FBX in FBX- and FBX-PG-treated rats and mice was compared in this study. The results showed that the bioavailability (<i>F</i>) values of FBX were 210% and 159% in FBX-PG-treated rats and mice, respectively. The 2.10-fold greater total area under the plasma concentration–time curve from time zero to infinity (AUC<sub>0-inf</sub>) of FBX was due to the increased absorption [i.e., 2.60-fold higher the first peak plasma concentration (<i>C</i><sub>max,1</sub>) at 15 min] and entero-hepatic circulation of FBX [i.e., 1.68-fold higher the second peak plasma concentration (<i>C</i><sub>max,2</sub>) at 600 min] in FBX-PG-treated rats compared to the FBX-treated rats. The 1.59-fold greater AUC<sub>0-inf</sub> of FBX was due to a 1.65-fold higher <i>C</i><sub>max,1</sub> at 5 min, and a 1.15-fold higher <i>C</i><sub>max,2</sub> at 720 min of FBX in FBX-PG-treated mice compared to those in FBX-treated mice. FBX was highly distributed in the liver, stomach, small intestine, and lungs in both groups of mice, and the FBX distributions to the liver and lungs were increased in FBX-PG-treated mice compared to FBX-treated mice. The results suggest the FBX-PG has a suitable pharmacokinetic profile of FBX for improving its oral <i>F</i> value.https://www.mdpi.com/1999-4923/15/8/2167febuxostatFBX/L-pyroglutamic acid cocrystalspharmacokineticsbioavailability |
| spellingShingle | Jeong-Eun Yu Byoung Hoon You Mingoo Bae Seung Yon Han Kiwon Jung Young Hee Choi Evaluation of Pharmacokinetic Feasibility of Febuxostat/L-pyroglutamic Acid Cocrystals in Rats and Mice Pharmaceutics febuxostat FBX/L-pyroglutamic acid cocrystals pharmacokinetics bioavailability |
| title | Evaluation of Pharmacokinetic Feasibility of Febuxostat/L-pyroglutamic Acid Cocrystals in Rats and Mice |
| title_full | Evaluation of Pharmacokinetic Feasibility of Febuxostat/L-pyroglutamic Acid Cocrystals in Rats and Mice |
| title_fullStr | Evaluation of Pharmacokinetic Feasibility of Febuxostat/L-pyroglutamic Acid Cocrystals in Rats and Mice |
| title_full_unstemmed | Evaluation of Pharmacokinetic Feasibility of Febuxostat/L-pyroglutamic Acid Cocrystals in Rats and Mice |
| title_short | Evaluation of Pharmacokinetic Feasibility of Febuxostat/L-pyroglutamic Acid Cocrystals in Rats and Mice |
| title_sort | evaluation of pharmacokinetic feasibility of febuxostat l pyroglutamic acid cocrystals in rats and mice |
| topic | febuxostat FBX/L-pyroglutamic acid cocrystals pharmacokinetics bioavailability |
| url | https://www.mdpi.com/1999-4923/15/8/2167 |
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