Comparison of the pharmacokinetics of miconazole after administration via a bioadhesive slow release tablet and an oral gel to healthy male and female subjects

Abstract

AimsThe aim of this study was to compare salivary miconazole pharmacokinetics following once daily application of bioadhesive tablets (50 or 100 mg), vs the current treatment with a gel (3 times a day, 375 mg day -1 ). MethodsA three way cross over study was carried out in 18 healthy subjects (nine males, nine females) with a 1 week washout period between each treatment. Plasma and salivary pharmacokinetics of miconazole were assessed over a 24-h period. ResultsIn all subjects the tablets gave higher and more prolonged salivary miconazole concentrations than the gel. Thus salivary miconazole AUC(0,24 h) was 37.2 times greater for the 100 mg tablet (90% confidence interval [CI] 22.9, 60.5) and 18.9 times greater for the 50 mg tablet (CI 11.7, 30.6) compared with the gel. Similarly, C max was 17.2 times greater (CI 11.8, 25.2) and 7.8 times greater (CI 5.3, 11.4) for the 100 mg tablet and 50 mg tablet, respectively. Comparison of the 100 mg and 50 mg tablets gave ratios of 2.2 and 2.0 for C max and AUC(0,24 h), respectively (CI 1.5, 3.2 and 1.2, 3.2). The mean time that salivary miconazole concentrations were above 0.4 m g ml -1 (the concentration reached 3 h after application of the oral gel according to published data) or above 1.0 m g ml -1 (the MIC of some Candida species) was greater for both bioadhesive tablets than for the oral gel (10-14 h vs 1.5 h and 7 h vs 0.6 h). Only 19 plasma samples from eight subjects had concentrations of miconazole above 0.4 m g ml -1 . Ten of these were taken from five subjects after administration of the gel and nine from three subjects after administration of the tablets. ConclusionsThese data strongly support the further development of miconazole bioadhesive tablets as a sustained release formulation leading to improved antifungal exposure in the buccal cavity. A single daily application should improve compliance, whereas the low systemic absorption of miconazole will alleviate concerns regarding drug interactions and adverse effects.J.-M. Cardot et al. 34658 :4 Br J Clin Pharmacol

Interaction of miconazole oral gel with warfarin and cyclosporine in a patient with nephrotic syndrome

“…The increase of INR occurred 1-2 weeks after initiation of treatment with miconazole in previous report [6], which is compatible with the present case. Pharmacokinetic study with healthy volunteers also showed that the maximum plasma concentration of miconazole following repeated dosing of 125 mg oral gel formula was 0.4-1.0 lg/ml [7], which is comparable to our patient's result. We also found reduced bioavailability of CsA after termination of miconazole oral gel.…”

“…One possibility is absorption from intestine after swallowing. Oral miconazole gel dissolves in saliva [7]. Therefore, miconazole in swallowed oral gel and saliva might be absorbed from intestine.…”

Miconazole Revisited: New Evidence of Antifungal Efficacy from Laboratory and Clinical Trials

“…Miconazole in a 50 and 100 mg mucoadhesive tablet (miconazole Lauriad ® ) formulated for extended release was initially tested in healthy volunteers [28]. Both concentrations were used once daily and had significantly longer duration and higher saliva concentration than a commercially available miconazole gel used three times per day.…”

The Efficacy and Safety of Miconazole Nitrate Mucoadhesive Tablets versus Itraconazole Capsules in the Treatment of Oral Candidiasis: An Open-Label, Randomized, Multicenter Trial

“…After stopping the medication for 14 days, the miconazole nitrate group showed a tendency toward a higher “cure” rate than the itraconazole group (42.01% vs. 32.14%, respectively), although the difference was not significant at the end of the treatment (31.36% vs. 29.17%, respectively). This might be related to the slow-release system with high, sustained salivary concentrations obtained with the mucoadhesive tablets [19]. In this study, we defined “cure” as clinical cure combined with mycological eradication.…”