NIKP-Manidipine Mechanism of Action

Pharmacology: Pharmacodynamics: Molecular mechanism: Long-acting hypertensive effect by dilating blood vessels, mainly by calcium channel blockade.
Pharmacokinetics: Absorption: Bioavailability is 36 to 60%. Time to peak concentration: 2-4 hours for oral single dose, and Tmax was 6 hours after repeated oral administration (20 mg once a day for 8 days). Onset: Single dose, initial response in 15-45 minutes and duration is 24 hour.
Food increases bioavailability. The mean maximum concentration of manidipine was 4.65 and 7.65 ng/mL following administration of a 20 mg dose before and after breakfast respectively, in 6 healthy Asian volunteers. AUC values were 25.57 and 36.75 ng/h/mL before and after the meal. These result suggest a better bioavailability in non-fasting conditions.
In healthy Caucasian volunteers, the extent of absorption increased by about 50% when manidipine was administered after a standard breakfast, while Cmax and Tmax were not significantly altered. Therefore, administration after a standard breakfast increase the bioavailability of the drug without modifying the rate of absorption.
Distribution: Protein binding 99%.
Metabolism: Manidipine is extensively metabolized in the liver.
Excretion: Excretion via renal 31.4% and mainly excrete in the faeces (63.3%) within 24 hour. The elimination half-life is about 5-8 hours.
Bioequivalence Study in Japan: When a single oral dose of two tablets of NIKP-Manidipine tablet 10 mg or two tablets of the reference product (both tablets contain 20 mg of manidipine hydrochloride) was administered to healthy male adults during fasting with a cross-over method, the plasma concentrations of manidipine hydrochloride were measured. In a statistical analysis for the obtained pharmacokinetic parameters (AUC and Cmax), calculation results of 90% confidence intervals for the parameters were within a range between log (0.8) and log (1.25), demonstrating the bioequivalence of the two formulations.
Similarly, one tablet of NIKP-Manidipine tablet 20 mg or one tablet of the reference product (both tablets contain 20 mg of manidipine hydrochloride) showed bioequivalence between the two formulations. (See Tables 2, 3 and Figures 1, 2.)

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Plasma concentration and pharmacokinetic parameters such as AUC and Cmax may vary depending on study conditions including selection of subjects, body fluid sampling frequency/sampling time, etc.
Bioequivalence Study in Thailand: See Tables 4, 5 and Figures 3, 4.

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Conclusion: The test product of Manidipine Hydrochloride Tablets (10 mg) manufactured by Nichi-Iko Pharmaceutical Co., Ltd. Toyama plant 1, Japan and imported by Nichi-Iko (Thailand) Co., Ltd. was bioequivalence to the reference product of Madiplot 10 mg.

Click on icon to see table/diagram/image


Click on icon to see table/diagram/image

Conclusion: The test product of Manidipine Hydrochloride Tablets (20 mg) manufactured by Nichi-Iko Pharmaceutical Co., Ltd. Toyama plant 1, Japan and imported by Nichi-Iko (Thailand) Co., Ltd. was bioequivalence to the reference product of Madiplot 20 mg.