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

The efficacy and safety of two sustained-release formulations of nifed ipine, the coat-core system (NIF CC) and the gastrointestinal therapeu tic system (NIF GITS), were examined in 228 patients with mild-to-mode rate essential hypertension in this 16-week, multicenter, randomized, double-blind study. The coadministration of food affects the nifedipin e pharmacokinetics with differing magnitudes for the two formulations. To evaluate drug safety under the most rigorous circumstances, all me dication was given with food. After a 4-week placebo lead-in period, e ligible patients were randomized to a parallel-group treatment period of either NIF CC or NIF GITS, 30 mg daily with food for 4 weeks, follo wed by forced titration to nifedipine 60 mg daily for an additional 4 weeks. For the final 4-week period, half of the patients receiving eac h formulation were switched to the alternate formulation at a dose of 60 mg daily. Within treatment groups, all four blood pressure variable s (systolic and diastolic measurements for both trough and 24-hour per iods) demonstrated significant reductions (P < 0.05) from baseline (es tablished after the placebo lead-in period) for both formulations at e very subsequent visit and end point. When comparing the two formulatio ns, the mean change from baseline in 24-hour systolic and diastolic bl ood pressure measurements, determined by using ambulatory monitoring; was not statistically different for both doses (P > 0.05). The mean ch ange in trough blood pressure from baseline during the parallel-group treatment period was statistically significant in favor of NIF GITS fo r both the 30-mg and 60-mg doses (P < 0.05). The treatment-emergent ad verse-event rates for both formulations were similar during the parall el-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 coad ministered 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 pres sure measurements (P > 0.05), adverse events, or dropout rates. When p atients receiving NIF CC 60 mg were crossed over to NIF GITS 60 mg dai ly, 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 simil arly. Although NIF GITS exhibited a greater reduction in the trough bl ood 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 resp onse, or adverse reactions.