RT Journal Article SR Electronic T1 Dosing Time-Dependent Effect of Temocapril on the Mortality of Stroke-Prone Spontaneously Hypertensive Rats JF Journal of Pharmacology and Experimental Therapeutics JO J Pharmacol Exp Ther FD American Society for Pharmacology and Experimental Therapeutics SP 176 OP 181 DO 10.1124/jpet.105.092080 VO 316 IS 1 A1 Masahiko Nozawa A1 Koh-ichi Sugimoto A1 Masami Ohmori A1 Hitoshi Ando A1 Akio Fujimura YR 2006 UL http://jpet.aspetjournals.org/content/316/1/176.abstract AB This study was undertaken to evaluate a dosing time-dependent effect of temocapril, an angiotensin-converting enzyme (ACE) inhibitor, on the mortality of stroke-prone spontaneously hypertensive rats (SHRSP). Temocapril (1 mg/kg/day) prolonged the survival rate of these animals, with a maximum effect after dosing at the early resting period and a minimum effect after dosing at the early active period. The pharmacokinetics of temocaprilat, an active metabolite of temocapril, did not differ significantly between the two dosing times. However, the inhibition of ACE activity in serum and organs (brain and aorta) and the reduction of blood pressure were significantly greater after dosing at the early resting period than at the early active period. These data suggest that the effect of temocapril on the mortality of SHRSP depends on the time of dosing, with a maximum effect seen after dosing at the early resting period. Dosing time-dependent differences in the pharmacodynamics of temocapril might be involved in explaining this phenomenon. The American Society for Pharmacology and Experimental Therapeutics