Cronidipine

LF 2-0254 is a 1,4-dihydropyridine calcium antagonist with a slow onset of action. The pharmacokinetics of [14C]LF 2-0254 were studied in rats and dogs. A sensitive high-performance liquid chromatographic method using liquid scintillation counting was developed for the quantitation of labelled LF 2-0254 in plasma. The peak height of the internal standard in the chromatogram was measured by UV detection and the mobile phase containing the chromatographic peak of [14C]LF 2-0254 was collected and counted for radioactivity. The concentration of labelled drug in the plasma was then determined using a calibration graph constructed from the determination of [14C]LF 2-0254 of known specific activities. The limit of determination was dependent on the specific activity of the drug administered. This method permits the measurement of the radioactive drug in biological fluids.

LF 2.0254 (I) is a new dihydropyridine calcium-channel blocker with a long-lasting antihypertensive action in spontaneously hypertensive rats.In acute experiments, LF 2.0254 was shown to be more potent than nifedipine and nicardipine in reducing blood pressure after i.v. and oral administration, with less tachycardia.The hypotensive effects of LF 2.0254 (10 mg/kg) lasted for >24 h, whereas the blood pressure-lowering effects of nifedipine and nicardipine (10 mg/kg) had disappeared after 6 h.LF 2.0254 given orally once a day at 10 mg/kg for 14 days to spontaneously hypertensive rats, led to a marked and persistent decrease in blood pressure, with no changes in heart rate.In an attempt to prevent the development of hypertension, LF 2.0254 (3 and 10 mg/kg) was given once a day for 8 wk to 5 wk-old SHR.On the last day of treatment, LF 2.0254 had markedly reduced blood pressure over a 24 h period, however, there was no reduction of left ventricular hypertrophy, since body weight and left ventricular weight were not different between control and treated groups.