Therapeutic Differences in 24‐h Ambulatory Blood Pressures in Patients Switched Between Bioequivalent Nifedipine Osmotic Systems With Differing Delivery Technologies

Figures

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  Figure 1. Similar appearance, differing delivery technologies. Most patients were unaware that substitutions were made by their pharmacies back and forth between Nifedipine‐GITS (zero‐order delivery) on the left, and Mylan‐Nifedipine‐XL (first‐order delivery) on the right.

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  Figure 2. Flowchart of treatment assignment and timing of ambulatory blood pressure monitor (ABPM) assessments. Vertical arrows mark time of study initiation and ABPM measurements for either Mylan‐Nifedipine‐XL (Mylan) or Nifedipine‐GITS (N‐GITS).

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  Figure 3. Curves for ABPM data plotted using the local regression LOESS function in R statistical software. Readings from 64 timepoints over 24 h for systolic and diastolic blood pressure (SBP and DBP) and heart rate (HR) provided 2,560 values for each parameter from 20 patients over two study periods. Solid‐red lines represent data fit from Mylan‐Nifedipine‐XL. Dashed‐green lines represent data fit from Nifedipine‐GITS. SBP curves for two patients are statistically different and continue to further separate during the terminal 8 h (nocturnal period) of the dosing interval, as delivery from Mylan‐Nifedipine‐XL is predicted to decline in a first‐order pattern. DBP curves follow a similar pattern, but are less affected by action of dihydropyridines and were not statistically different. HR remains clinically unaffected by constant, low‐rate delivery of nifedipine, varying by only 15 bpm over the course of the day.

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  Figure 4. Plots of mixed‐effects fit of SBP data over time using GAMM function in R statistical software. Solid‐red lines represent data fit from Mylan‐Nifedipine‐XL. Dashed‐green lines represent data fit from Nifedipine‐GITS. There is a clear, statistically significant separation of 3 ± 1.1 mmHg (P = 0.0173) between the curves of best population fit for each formulation, which was even larger during the last 8 h of the dosing interval.