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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 
 
 

Analysis of the daily variation in blood pressure and pharmacokinetics after single or repeated administration of clentiazem to patients with essential hypertension.

Clentiazem (TA-3090, CAS 96125-53-0), a new benzothiazepine Ca++ antagonist, was orally administered to inpatients with essential hypertension at a dose of 30 mg at 8:00 a.m. once (n = 5) or daily for 2 weeks (n = 22). After administration of the medication, the daily variations in blood pressure and pulse rate were monitored using a portable blood pressure recorder, and plasma concentrations of clentiazem were determined by HPLC. 1. In the single administration study, an antihypertensive effect was observed between 4 and 12 h with a peak approximately 8 h after administration. After the single dose, the diurnal pulse rate was higher than the pretreatment level, but it was not correlated with the antihypertensive effect. 2. In the repeated administration study, both the systolic and diastolic blood pressures showed significant decreases after administration throughout the day (p less than 0.01). The nocturnal antihypertensive effect was weaker than the diurnal effect, and the minimum decrease/maximum decrease ratio in a day was 0.52 for both systolic and diastolic pressures. The pulse rate decreased slightly during certain time intervals after administration (p less than 0.01 or p less than 0.05), but those were slight changes. 3. As to the pharmacokinetic profile clentiazem showed a long-lasting plasma level, the tmax was 6.8 +/- 1.1 h for the single treatment and 6.9 +/- 1.6 h for the repeated treatment; the Cmax was 16.9 +/- 6.1 ng/ml and 19.3 +/- 8.8 ng/ml, respectively; and the t1/2 was 6.6 +/- 1.5 h and 12.5 +/- 5.4 h, respectively. The plasma level profiles for single and repeated administrations were similar.(ABSTRACT TRUNCATED AT 250 WORDS)[1]

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