Comparing pharmacokinetics and metabolism of diltiazem in normotensive Sprague Dawley and Wistar Kyoto rats vs. spontaneously hypertensive rats in vivo

Yeung, P. K. F.; Alcos, Angelita; Marcoux, Tanya; Tang, Jinglan

doi:10.1515/dmdi.2011.012

Cited by 1 publication

(1 citation statement)

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“…One of the first generation calcium channel blockers is diltiazem (DTZ), which is clinically proven effective for hypertension and angina, and has potential for stroke prevention [ 6 , 7 ]. It is also often used as a probe to study pharmacokinetics and pharmacodynamic interactions with the calcium channel blockers [ 8 , 9 , 10 , 11 ]. In addition to lowering blood pressure, DTZ has significant negative chronotropic and inotropic effects, which are important for patients with cardiac arrhythmias and those who need beta-blockers [ 12 ].…”

Section: Introductionmentioning

confidence: 99%

Diltiazem Reduces Mortality and Breakdown of ATP in Red Blood Cell Induced by Isoproterenol in a Freely Moving Rat Model in Vivo

Yeung

Seeto

2014

Metabolites

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The benefit of calcium channel blockers for cardiovascular prevention against heart attack and stroke has not been firmly supported. We investigated the possible cardiovascular protective effect of diltiazem (DTZ) against injury induced by isoproterenol using a freely moving rat model in vivo. Sprague Dawley rats were injected subcutaneously (sc) with either 5 or 10 mg/kg of DTZ, or saline as control, twice daily for five doses. One hour after the last injection, a single dose of isoproterenol (30 mg/kg) was injected sc to each rat. Blood samples were collected serially for 6 h for measurement of adenine nucleotides (ATP, ADP and AMP) in red blood cell (RBC) by a validated HPLC. The study has shown isoproterenol induced 50% mortality and also increased RBC concentrations of AMP from 0.04 ± 0.02 to 0.29 ± 0.21 mM at the end of the experiment (p < 0.05). Treatment with 10 mg/kg of DTZ reduced mortality from 50% to <20% and attenuated the increase of RBC concentrations of AMP from +0.25 ± 0.22 in the control rats to +0.072 ± 0.092 mM (p < 0.05). The study concluded that 10 mg/kg of DTZ reduced mortality and breakdown of ATP induced by isoproterenol in rats.

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