ABSTRACT
BACKGROUND: Irritable bowel syndrome with constipation (IBS-C) significantly decreases quality of life and the ability to perform daily living activities. AIM: To demonstrate the long-term safety, tolerability and patient outcomes of lubiprostone in patients with IBS-C. METHODS: This extension study enrolled 522 IBS-C patients who had completed one of two randomised phase 3 studies. All enrolled patients received open-label lubiprostone orally for 36-weeks (8 mcg, twice daily). The primary objective was the assessment of long-term safety and tolerability, monitored via adverse events (AEs), laboratory parameters and vital signs. Additional outcome endpoints included monthly responder rates and patient evaluations of IBS-C symptom severity and impact on quality of life. RESULTS: The evaluable safety population comprised of 520 patients; 476 of which had patient reported outcome data available. The overall safety profile of lubiprostone during this study was similar to that observed in the preceding phase 3 studies. The most common AEs were diarrhoea (11.0%), nausea (11.0%), urinary tract infection (9.0%), sinusitis (9.0%) and abdominal distention (5.8%). Diarrhoea and nausea were the most common treatment-related AEs. No serious AEs were considered treatment-related. Seventeen patients discontinued due to a treatment-related AE, of which diarrhoea and nausea accounted for six (1.2%) and three (0.6%) respectively. For responder rates and patient-evaluated parameters (n = 476), all groups experienced significant improvements from baseline, with initial improvements maintained throughout the study. CONCLUSION: In patients with irritable bowel syndrome with constipation, lubiprostone 8 mcg twice daily was found to be safe and well tolerated over 9-13 months of treatment.
Subject(s)
Alprostadil/analogs & derivatives , Constipation/drug therapy , Gastrointestinal Agents/adverse effects , Irritable Bowel Syndrome/drug therapy , Activities of Daily Living , Adult , Alprostadil/adverse effects , Chloride Channel Agonists , Chloride Channels/adverse effects , Defecation/drug effects , Female , Humans , Lubiprostone , Male , Middle Aged , Quality of Life/psychology , Time Factors , Treatment OutcomeABSTRACT
AIM: The influence of niflumic acid (NFA), a Cl(-)channel antagonist, on the membrane potentials in smooth muscle cells (SMC) of the cochlear spiral modiolar artery (SMA) in guinea pigs was examined. METHODS: The intracellular recording and whole-cell recording technique were used to record the NFA-induced response on the acutely-isolated SMA preparation. RESULTS: The SMC had 2 stable but mutually convertible levels of resting potentials (RP), that is, one was near -45 mV and the other was approximately -75 mV, termed as low and high RP, respectively. The bath application of NFA could cause a hyperpolarization in all the low RP cells, but had little effect on high RP cells. The induced responses were concentration-dependent. Large concentrations of NFA (>or=100 micromol/L) often induced a shift of a low RP to high RP in cells with an initial RP at low level, and NFA (up to 100 micromol/L) had little effect on the membrane potentials of the high RP cells. However, when the high RP cells were depolarized to a level beyond -45 mV by barium and ouabain, NFA hyperpolarized these cells with the similar effect on those cells initially being the low RP. The NFA-induced response was almost completely blocked by charybdotoxin, iberiotoxin, tetraethylammonium, 1,2-bis(2- aminophenoxy) ethane-N,N,N',N'-tetraacetic acid tetrakis acetoxymethyl ester, but not by 4-aminopyridine, barium, glipizide, apamin, ouabain, and CdCl2. CONCLUSION: NFA induces a concentration-dependent reversible hyperpolarization in SMC in the cochlear SMA via activation of the Ca2+-activated potassium channels.
