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Phosphate buffer interferes dissolution of prazosin hydrochloride in compendial dissolution testing
Drug Metab Pharmacokinet. 2023 Jun 10;51:100519. doi: 10.1016/j.dmpk.2023.100519. Online ahead of print.ABSTRACTThe purpose of this study was to elucidate the lack of supersaturation behavior in the dissolution profile of prazosin hydrochloride (PRZ-HCl) in the compendial dissolution test. The equilibrium solubility was measured by a shake-flask method. Dissolution tests were performed by a compendial paddle method with a phosphate buffer solution (pH 6.8, 50 mM phosphate). The solid form of the residual particles was identified by Raman spectroscopy. In the pH range below 6.5, the equilibrium solubility in phosphate buffe...
Source: Drug Metabolism and Pharmacokinetics - July 2, 2023 Category: Drugs & Pharmacology Authors: Hiroshi Sudaki Katsuyoshi Fujimoto Koichi Wada Kiyohiko Sugano Source Type: research

Contribution analysis of metabolic tissues on systemic exposure of an active metabolite after oral administration of verapamil using a stable isotope-labeled compound
Drug Metab Pharmacokinet. 2023 May 19;51:100514. doi: 10.1016/j.dmpk.2023.100514. Online ahead of print.ABSTRACTThe present study illustrates the advantage of an isotope-IV study for the contribution analysis of metabolic tissues on systemic exposure of metabolites. A model parent drug, verapamil (VER), and its metabolite, norverapamil (Nor-VER), were used. This isotope-IV study used rats with and without the pre-treatment of the CYP inhibitor 1-aminobenzotriazole (ABT), was performed by the oral administration of VER (1 mg/kg) combined with the intravenous administration of stable isotope-labeled VER (VER-d6, 0.005 mg/kg)...
Source: Drug Metabolism and Pharmacokinetics - June 26, 2023 Category: Drugs & Pharmacology Authors: Makoto Kataoka Shota Ohshiro Keiko Minami Tsubasa Hasegawa Haruki Higashino Toshihide Takagi Kazutaka Togashi Kuninori Mutaguchi Shinji Yamashita Source Type: research