Citation

Millington DJ, Villanueva C, Obirek J, Kaufman J, Smith C. Basic Clin. Pharmacol. Toxicol. 2010; 107(2): 701.

Affiliation

St Charles Pharmaceuticals, Inc., Florida Labs, Alachua, FL, USA.

Copyright

(Copyright © 2010, Nordic Pharmacological Society, Publisher John Wiley and Sons)

DOI

10.1111/j.1742-7843.2010.00562.x

PMID

20406209

Abstract

We investigated the safety pharmacological effects, that is, motor co-ordination and cardiac arrhythmia of either SCP-123 and/or gabapentin in this study. In addition, we characterized the acute toxicological effect of SCP-123 and acetaminophen (APAP) and evaluated the pharmacokinetic properties of SCP-123 in both in vivo and in vitro test systems. Motor co-ordination was not affected by SCP-123 up to 1000 mg/kg or gabapentin up to 500 mg/kg in naïve rats; however, 1000 mg/kg gabapentin produced a reduction in latency after 1 hr. A dose of 100 muM SCP-123 inhibited human ether-à-go-go-related gene current by 0.5 +/- 0.2% at 10 muM and 0.2 +/- 0.1%. There were no significant changes in plasma glutamic-oxaloacetic transaminase and glutamate-pyruvate transaminase levels at 3 g/kg SCP-123 or 3 g/kg APAP; however, 3 g/kg APAP decreased liver glutathione levels, from control after 18 hr of dosing. SCP-123 produced weak to moderate binding to human plasma proteins ranging from 64% to 80% bound. SCP-123 produced no inhibition on CYP2C9 and CYP2C19, weak inhibition on CYP2E1, CYP3A4 and CYP2D6, and moderate inhibition on CYP1A2 and CYP2A6. SCP-123 has a half-life of 2.3 hr and a 40% bioavailability. These data indicate that acute SCP-123 may have a better safety profile than gabapentin or APAP and; therefore, SCP-123 may be of clinical use.

Language: en