The use of new approach by a cubic curve fitting method to calculate the trough/peak ratios for manidipine hydrochloride in hypertensives

Objective: To examine the slow onset efficacy of a dihydropyridine antihypertensive agent manidipine hydrochloride by the trough/peak in relation to the treatment day, we applied a new calculation method named 'the cubic curve fitting method' to obtain the trough/peak ratios (T/P ratio). Design: New calculation method for examining the antihypertensive effect of manidipine. Setting: Institutional blood pressure protocol. Main outcome measure: The T/P ratios of the whole group calculated in relation to treatment day. Results: Ambulatory blood pressure monitoring (ABPM) was performed in 6 inpatients with mild essential hypertension. After an initial 2-week run-in period using a placebo, they received 20 mg of manidipine once a day. ABPM was performed on the last placebo day, and then on the 3rd, 10th and 17th days after the commencement of manidipine administration. The blood pressure circadian profiles gradually decreased during the treatment period. The T/P ratios were calculated with the cubic curve fitting method, a new approach we have developed. The T/P gradually improved during the treatment period, being 0.36 on the 3rd day, 0.69 on the 10th day and 0.76 on the 17th day. Conclusion: A new approach for calculating the T/P ratio which demonstrates the profiles of decreases in blood pressure after dosing is proposed. We applied the method on small number of hypertensive patients. These results suggest that the antihypertensive effect of manidipine requires more than 10 days to manifest its full effect and that manidipine improves the T/P ratio, namely, it reduces circadian variations which mediates hypertensive target organ damage.