Research Article| Volume 17, ISSUE 1, P12-29, January 1995

The efficacy and safety of once-daily nifedipine: the coat-core formulation compared with the gastrointestinal therapeutic system formulation in patients with mild-to-moderate diastolic hypertension

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      The efficacy and safety of two sustained-release formulations of nifedipine, the coat-core system (NIF CC) and the gastrointestinal therapeutic system (NIF GITS), were examined in 228 patients with mild-to-moderate essential hypertension in this 16-week, multicenter, randomized, double-blind study. The coadministration of food affects the nifedipine pharmacokinetics with differing magnitudes for the two formulations. To evaluate drug safety under the most rigorous circumstances, all medication was given with food. After a 4-week placebo lead-in period, eligible patients were randomized to a parallel-group treatment period of either NIF CC or NIF GITS, 30 mg daily with food for 4 weeks, followed by forced titration to nifedipine 60 mg daily for an additional 4 weeks. For the final 4-week period, half of the patients receiving each formulation were switched to the alternate formulation at a dose of 60 mg daily. Within treatment groups, all four blood pressure variables (systolic and diastolic measurements for both trough and 24-hour periods) demonstrated significant reductions (P < 0.05) from baseline (established after the placebo lead-in period) for both formulations at every subsequent visit and end point. When comparing the two formulations, the mean change from baseline in 24-hour systolic and diastolic blood pressure measurements, determined by using ambulatory monitoring, was not statistically different for both doses (P > 0.05). The mean change in trough blood pressure from baseline during the parallel-group treatment period was statistically significant in favor of NIF GITS for both the 30-mg and 60-mg doses (P < 0.05). The treatment-emergent adverse-event rates for both formulations were similar during the parallel-group period, with the exception of dizziness, which was higher for patients receiving NIF CC. Both formulations were well tolerated and reduced blood pressure over the 24-hour dosing interval even when coadministered with food. When half of the patients receiving NIF GITS 60 mg daily were randomly crossed over to NIF CC 60 mg daily, there were no significant changes in either the trough or 24-hour mean blood pressure measurements (P > 0.05), adverse events, or dropout rates. When patients receiving NIF CC 60 mg were crossed over to NIF GITS 60 mg daily, they exhibited no significant change in diastolic blood pressure (P > 0.05). This study demonstrated that when given with food, both NIF CC and NIF GITS reduce 24-hour mean blood pressure measurements similarly. Although NIF GITS exhibited a greater reduction in the trough blood pressure, patients could be crossed over from NIF GITS 60 mg daily to NIF CC 60 mg daily without any change in dose, blood pressure response, or adverse reactions.
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