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Evaluation of Pharmacokinetic Feasibility of Febuxostat/L-pyroglutamic Acid Cocrystals in Rats and Mice.
Yu, Jeong-Eun; You, Byoung Hoon; Bae, Mingoo; Han, Seung Yon; Jung, Kiwon; Choi, Young Hee.
Afiliação
  • Yu JE; College of Pharmacy and Integrated Research Institute for Drug Development, Dongguk University_Seoul, 32 Dongguk-ro, Ilsandong-gu, Goyang-si 10326, Gyeonggi-do, Republic of Korea.
  • You BH; College of Pharmacy and Integrated Research Institute for Drug Development, Dongguk University_Seoul, 32 Dongguk-ro, Ilsandong-gu, Goyang-si 10326, Gyeonggi-do, Republic of Korea.
  • Bae M; College of Pharmacy and Integrated Research Institute for Drug Development, Dongguk University_Seoul, 32 Dongguk-ro, Ilsandong-gu, Goyang-si 10326, Gyeonggi-do, Republic of Korea.
  • Han SY; College of Pharmacy and Integrated Research Institute for Drug Development, Dongguk University_Seoul, 32 Dongguk-ro, Ilsandong-gu, Goyang-si 10326, Gyeonggi-do, Republic of Korea.
  • Jung K; College of Pharmacy, CHA University, 335 Pangyo-ro, Bundang-gu, Seongnam-si 13488, Gyeonggi-do, Republic of Korea.
  • Choi YH; Oncobix Co., Ltd., 120 Heungdeokjungang-ro, Giheung-gu, Yongin-si 16950, Gyeonggi-do, Republic of Korea.
Pharmaceutics ; 15(8)2023 Aug 21.
Article em En | MEDLINE | ID: mdl-37631381
Febuxostat (FBX), a selective xanthine oxidase inhibitor, belongs to BCS class II, showing low solubility and high permeability with a moderate F 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 (F) 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 (AUC0-inf) of FBX was due to the increased absorption [i.e., 2.60-fold higher the first peak plasma concentration (Cmax,1) at 15 min] and entero-hepatic circulation of FBX [i.e., 1.68-fold higher the second peak plasma concentration (Cmax,2) at 600 min] in FBX-PG-treated rats compared to the FBX-treated rats. The 1.59-fold greater AUC0-inf of FBX was due to a 1.65-fold higher Cmax,1 at 5 min, and a 1.15-fold higher Cmax,2 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 F value.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Ano de publicação: 2023 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Ano de publicação: 2023 Tipo de documento: Article