Yu, J.-E.; You, B.H.; Bae, M.; Han, S.Y.; Jung, K.; Choi, Y.H. Evaluation of Pharmacokinetic Feasibility of Febuxostat/L-pyroglutamic Acid Cocrystals in Rats and Mice. Pharmaceutics2023, 15, 2167.
Yu, J.-E.; You, B.H.; Bae, M.; Han, S.Y.; Jung, K.; Choi, Y.H. Evaluation of Pharmacokinetic Feasibility of Febuxostat/L-pyroglutamic Acid Cocrystals in Rats and Mice. Pharmaceutics 2023, 15, 2167.
Yu, J.-E.; You, B.H.; Bae, M.; Han, S.Y.; Jung, K.; Choi, Y.H. Evaluation of Pharmacokinetic Feasibility of Febuxostat/L-pyroglutamic Acid Cocrystals in Rats and Mice. Pharmaceutics2023, 15, 2167.
Yu, J.-E.; You, B.H.; Bae, M.; Han, S.Y.; Jung, K.; Choi, Y.H. Evaluation of Pharmacokinetic Feasibility of Febuxostat/L-pyroglutamic Acid Cocrystals in Rats and Mice. Pharmaceutics 2023, 15, 2167.
Abstract
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 improving 4-fold increase of the FBX solubility. Nevertheless, in vivo pharmacokinetic property of FBX-PG has 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 F values of FBX were 210% and 159% in FBX-PG rats and mice, respectively. The 2.10-fold greater AUC of FBX was due to the increased absorption (i.e., 2.60-fold higher Cmax,1 at 15 min) and entero-hepatic circulation of FBX (i.e., 1.68-fold higher Cmax,2 at 600 min) in FBX-PG rats compared to the FBX rats. The 1.59-fold greater AUC of FBX was due to a 1.65-fold higher Cmax,1 at 5 min, and 1.15-fold higher Cmax,2 at 720 min of FBX in FBX-PG mice than those in FBX 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 mice compared to FBX mice. The results suggest the FBX-PG has a suitable pharmacokinetic profile of FBX for improving its oral F value.
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