Food effect on the oral bioavailability of Manidipine: single dose, randomized, crossover study in healthy male subjects

Abstract

The effect of food on the oral bioavailability of a manidipine 20 mg tablet was studied after a single administration in 12 male healthy subjects. The clinical trial was conducted as an open, randomised, crossover study. In two different administration sessions, the subjects received a 20 mg manidipine tablet either in the fasting state or after a standardized breakfast. Plasma samples were collected before and at different times after each administration for up to 24 h. The concentrations of manidipine and its pyridine metabolite (M-XIII metabolite) were determined by HPLC with coulometric detection. The tolerability of manidipine was good. Only two cases of mild headache, one with each treatment, were reported. Food significantly improved the absorption, with an increase in AUC from 19.1 to 27.2 ng.h/ml (geometric mean, p<0.01) but did not modify the rate of absorption (tmax unchanged, median = 1.5 h). Peak plasma concentration was also increased (from 6.2 to 7.8 ng/ml), but the difference was not statistically significant (p=0.18). Other pharmacokinetic parameters (apparent elimination half-life and mean residence time) remained unchanged. The increase in bioavailability of manidipine administered with food is related to its high lipophilicity and may be explained through a solubilization effect produced by food and bile secretions.

Single Oral Dose Pharmacokinetic Interaction Study of Manidipine and Delapril in Healthy Volunteers

“…The objective of the study was to compare the pharmacokinetics of oral manidipine and delapril when taken alone or simultaneously, after a standard breakfast. The latter allowed maximising the exposure to manidipine since its bioavailability is about 50 % higher when taken with food [3]. The bioavailability of manidipine was slightly decreased by concomitant administration of delapril, however, the 90 % confidence intervals remained within the standard limits allowing the conclusion of lack-ofinteraction; t max and t 1/2 were unaltered.…”

“…1). Food enhances the oral bioavailability of manidipine by about 50 % without impact on the absorption rate [2,3].…”

Repurposing the clinically approved calcium antagonist manidipine dihydrochloride as a new early inhibitor of human cytomegalovirus targeting the Immediate-Early 2 (IE2) protein

“…However, it might be also possible that the mechanism of viral inhibition by MND does not involve its calcium antagonistic effects, and that a completely new target/function in HCMV replication cycle is affected by this drug. Maximum plasma concentrations (Cmax) in human adults for an oral dose of 20 mg of MND were reported to be around 7 ng/ml (Rosillon et al, 1998), corresponding to ∼10 μM. This is above the effective concentrations determined in this study to obtain 50%, and even 90% inhibition of viral replication (EC50 = 3.09 μM and EC90 = 6.68 μM, respectively; Table 1 and Fig.…”

Cannabinoid Receptor Agonist 13, a Novel Cannabinoid Agonist: First in Human Pharmacokinetics and Safety

“…CRA13 behaves in a manner similar to manidipine, another highly lipophilic (log P ϭ 5.18) drug, because of which the food absorption improved significantly, with 25 and 50% increases in C max and AUC, respectively, but with no effect on t max . The authors suggested that the increase in manidipine bioavailability was related to its lipophilicity and could be explained through a solubilization effect produced by food and bile secretions (Rosillon et al, 1998). …”