Prediction of the lower esophageal sphincter pressure after oral molsidomine by sydnonimine plasma concentrations.
OBJECTIVE
Recent studies suggest that endogenous nitric oxide decreases lower esophageal sphincter pressure (LESP). Substances leading to the formation of nitric oxide, such as molsidomine, decreases the human LESP. It is not yet clear whether this reduction is related to plasma concentrations of molsidomine, the nitrate-active substance sydnonimine (SIN-1) or to serum concentrations of nitrate/nitrite (NOx) as a stable end-product of volatile nitric oxide.


METHODS
We performed a double blind controlled crossover trial in 8 healthy male volunteers. Plasma concentrations of molsidomine, SIN-1 and serum concentrations of NOx as well as esophageal manometry were determined.


RESULTS
Mean basal LESP was significantly decreased from 25.4 +/- 2.8 mmHg to 21.9 +/- 2.7 mmHg and 21.4 +/- 2.6 mmHg 2 and 3 hours after molsidomine administration, respectively (mean +/- SEM; n = 8; p < 0.05). The maximum decrease of LESP from the baseline within 1-4 hours after molsidomine administration was 7.6 +/- 1.5 mmHg (mean +/- SEM; n = 8; p < 0.01). The decrease of the LESP correlated significantly with plasma concentrations of SIN-1 (r = -0.53; p = 0.002). NOx levels remained unchanged.


CONCLUSIONS
Molsidomine decreases the LESP and plasma concentrations of the active metabolite SIN-1 may predict the potency of molsidomine to lower LESP. NOx was useless as a control metabolite to measure the LESP in response to molsidomine in healthy volunteers.
Stoschus
B
B
Medizinische Klinik-Allgemeine Innere Medizin, University of Bonn, Germany.
Fernandez
I
I
Heller
J
J
Neubrand
M
M
Sauerbruch
T
T
D000284:Administration, Oral; D000328:Adult; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004943:Esophagogastric Junction / Q000187:drug effects*; D006801:Humans; D008297:Male; D008365:Manometry; D008981:Molsidomine / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D009569:Nitric Oxide / Q000097:blood; D010528:Peristalsis / Q000187:drug effects
D009569:Nitric Oxide; C002385:linsidomine; D008981:Molsidomine