In vivo effects of nifedipine and BAY 1 8201 on ceruletide induced gallbladder contraction.
Studies in animals suggest that calcium channel blockers may influence gallbladder contraction. In order to study possible actions in man we examined by ultrasonography the effects of two dihydropyridine derivatives, i.e. nifedipine (20 mg p. o.) and BAY 1 8201 (100 mg p.o.) on ceruletide induced human gallbladder contraction in 9 healthy male volunteers in a randomized, double-blind, three fold crossover study (latin square design). Blood samples for the measurement of plasma drug concentrations were drawn before and at regular intervals up to 8 h after drug ingestion. Ceruletide decreased gallbladder volumes by 52.1 +/- 8.2% (mean +/- 1 SEM) after nifedipine, 53.1 +/- 8.1% after BAY 1 8201 and by 59.3 +/- 10.1% after placebo (NS). Peak plasma concentrations of 53.7 x/: 2.3 ng/ml (geometric mean x/: geometric standard deviation) and of 35.5 x/: 1.5 ng/ml were reached after oral application of nifedipine and BAY 1 8201, respectively. We conclude that human gallbladder contraction in response to ceruletide is not markedly influenced by dihydropyridine derivates in the dosages used in this study. The results reported here stress the importance of calcium released from intracellular stores for the contractility of smooth muscle in the human gallbladder.
Porschen
R
R
Department of Gastroenterology, University of Düsseldorf.
Pieper
S
S
Bernhardt
L
L
Schade
B
B
Wienbeck
M
M
D000328:Adult; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000493:pharmacokinetics / Q000494:pharmacology*; D002108:Ceruletide / Q000494:pharmacology*; D002986:Clinical Trials as Topic; D005704:Gallbladder / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009543:Nifedipine / Q000493:pharmacokinetics / Q000494:pharmacology*; D009930:Organic Chemicals; D011897:Random Allocation; D014463:Ultrasonography
D002121:Calcium Channel Blockers; D009930:Organic Chemicals; C059264:BAY 1 8201; D002108:Ceruletide; D009543:Nifedipine