Effects of nifedipine on esophageal motor function in humans: correlation with plasma nifedipine concentration

We studied the effects of the calcium-channel blocker nifedipine on esophageal smooth muscle function in 10 normal volunteers. Lower esophageal sphincter pressure and relaxation and esophageal contraction amplitude, peristalsis, velocity, and duration after wet swallows were determined before and for 120 min after the sublingual/buccal administration of placebo and of nifedipine in doses of 10, 20, 30, and 40 mg. Blood samples for measurement of plasma nifedipine concentration were obtained at baseline and every 30 min during this 120-min period. Nifedipine led to decreases in sphincter pressure of 13.3%, 29.9%, 34.3%, and 35.1% as the dose was increased from 10 mg to 40 mg. These changes were significantly (p less than 0.05) different from baseline and placebo for the 20-, 30-, and 40-mg doses and were more sustained with the higher doses, lasting as long as 90 min. Contraction amplitude fell 5.3%, 5.9%, 13.5%, and 19.6% at the corresponding doses. These changes were significantly (p less than 0.05) different from baseline and placebo only for the 30- and 40-mg doses, with the effect lasting up to 60 min. Peak plasma nifedipine concentration ranged from 28.7 +/- 3.7 ng/ml (mean +/- SEM) after 10 mg to 138.7 +/- 43.7 ng/ml after 40 mg of the drug, and occurred at either the 30- or 60-min measurement. The mean percent of decrease in sphincter pressure and contraction amplitude in the esophageal body correlated (p less than 0.001) with plasma nifedipine levels. There were no changes in sphincter relaxation or in peristalsis, velocity, or duration of contraction with any dose of nifedipine. It is concluded that (a) nifedipine significantly decreases lower esophageal sphincter pressure and contraction amplitude in the body of the esophagus, (b) the effect on sphincter pressure requires a lower dose of nifedipine and is more marked than that on contraction amplitude, and (c) the effects on both sphincter pressure and contraction amplitude correlate with plasma nifedipine levels. Calcium-channel blockers such as nifedipine may have a role in the treatment of motility disorders of the lower esophageal sphincter or esophageal body, and further controlled clinical studies are indicated.