Characterization of microminipig as a laboratory animal for safety pharmacology study by analyzing fluvoxamine-induced cardiovascular and dermatological adverse reactions.

Characterization of microminipig as a laboratory animal for safety pharmacology study by analyzing fluvoxamine-induced cardiovascular and dermatological adverse reactions. Cardiovasc Toxicol. 2019 Feb 08;: Authors: Tanikawa Y, Hagiwara-Nagasawa M, Kambayashi R, Goto A, Chiba K, Kitta K, Hoshiai K, Izumi-Nakaseko H, Naito AT, Sugiyama A Abstract Fluvoxamine is a selective serotonin-reuptake inhibitor, of which IC50 values for serotonin- and noradrenaline-uptake process were reported to be 3.8 and 620 nmol/L, respectively, also known to directly inhibit cardiac Na+, Ca2+, and K+ channels. We characterized microminipig as a laboratory animal by analyzing fluvoxamine-induced cardiovascular and dermatological responses under halothane anesthesia. Fluvoxamine maleate was infused in doses of 0.1, 1, and 10 mg/kg over 10 min with a pause of 20 min (n = 4). The peak plasma concentrations were 35, 320, and 1906 ng/mL, of which free plasma concentrations were estimated as 20, 187, and 1108 nmol/L, respectively. The low and middle doses did not alter any cardiovascular variable. The high dose increased heart rate and mean blood pressure, prolonged QRS width, but shortened QT interval, whereas no significant change was detected in PR interval or QTcF. Moreover, it induced systemic erythema on the skin. Pretreatment of H1/5-HT2A antagonist cyproheptadine hydrochloride sesquihydrate in a dose of 0.3 mg/kg significantly attenuated the flu...
Source: Cardiovascular Toxicology - Category: Cardiology Authors: Tags: Cardiovasc Toxicol Source Type: research