Serum levels and possible hemodynamic effects following the anorectal application of an ointment containing nifedipine and lidocaine: a study on healthy volunteers.

OBJECTIVES: This study aimed to assess whether topical anorectal application of an ointment containing nifedipine (0.3% w/w) and lignocaine (lidocaine) [1.5% w/w] to healthy adult volunteers gives rise to pharmacologically relevant serum levels of the active ingredients and has any haemodynamic effects or side effects. METHODS: A dose of 3g of the ointment was circumferentially applied inside the anus to 12 healthy volunteers every 12 hours for 7 days. Blood samples were collected at 0, 30, 60, 240, 480 and 720 minutes after the first application; in addition, blood samples were collected at days 1 and 7 after multiple applications. Serum concentrations of nifedipine, its main metabolites and lignocaine were determined by a new high-performance liquid chromatography method established for the purpose of the study. Volunteers' blood pressure, heart rate, ECG status and laboratory parameters were monitored throughout the study. RESULTS: Topical application of the ointment to healthy volunteers did not produce therapeutically significant serum levels of the active ingredients and/or their active metabolites. Indeed, chromatographic signals of the active ingredients and/or nifedipine metabolites were only sporadically observed, below the quantification limits for the method, and consistent with therapeutically negligible concentrations. No serious local or systemic adverse events were observed throughout the study, and no subjects developed arrhythmias or significant ECG changes. Neither blood pressure nor mean heart rate varied significantly after application of a single dose. After multiple doses, mean systolic and diastolic blood pressure remained close to baseline levels for the duration of the study. The mean heart rate after multiple doses was about 5% below baseline level at days 1 and 7; however, these differences were not statistically significant. CONCLUSION: This study demonstrates the safety of topical anorectal application of an ointment containing nifedipine (0.3% w/w) and lignocaine (1.5% w/w) to healthy volunteers.