Once-a-month treatment with a combination of mifepristone and the prostaglandin analogue misoprostol. (1/308)

In this two centre study, the efficacy of 200 mg mifepristone orally followed 48 h later by 0.4 mg misoprostol orally for menstrual regulation was investigated. The dose of mifepristone was taken the day before the expected day of menstruation. Each volunteer was planned to participate for up to 6 months. A plasma beta human chorionic gonadotrophin (HCG) was measured on the day of mifepristone intake. The study was disrupted prematurely due to low efficacy. In 125 treatment cycles the overall pregnancy rate was 17.6% (22 pregnancies) and the rate of continuing pregnancies (failure) was 4.0%. Eight women discontinued the study due to bleeding irregularities which were seen in 15 cycles (12%). These effects on bleeding pattern made the timing of treatment day difficult. Late luteal phase treatment with a combination of mifepristone and misoprostol is not adequately effective for menstrual regulation.  (+info)

Prevention of nonsteroidal anti-inflammatory drug-induced gastropathy: clinical and economic implications of a single-tablet formulation of diclofenac/misoprostol. (2/308)

Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used to manage arthritis. While controlling symptoms and improving quality of life, NSAID use is associated with gastroduodenal injury and a 2%-4% annual risk for symptomatic gastroduodenal ulceration, hemorrhage, and perforation. This requires clinicians to balance the efficacy of NSAIDs against the potential risk of serious gastrointestinal events. Identification and stratification of risk can help guide the optimal approach for arthritis management of individual patients or large populations such as managed care organizations. NSAID-induced gastroenteropathy carries considerable economic consequences; 46% of arthritis costs are related to managing serious adverse events. It is reasonable to assume that these costs may not be incurred if high-risk patients are recognized and optimally managed. Newer therapies with proven safety margins present an attractive option, especially for patients at higher risk. The single-tablet formulations of diclofenac and misoprostol (Arthrotec) offer an alternative in managing NSAID patients because of their inherent safety profile. Studies with diclofenac/misoprostol indicate its effectiveness in treating signs and symptoms of arthritis and in reducing the incidence of NSAID-induced gastroenteropathy. As such, this agent may provide improved medical and economic outcomes. This review discusses the clinical aspects of NSAID-induced gastroenteropathy, including available preventive therapies. Approaches to assessing patients' risk for developing complications, and the relationship of medical risk and economic outcomes, are also examined. Although not all patients require preventive therapy, patients with heightened risk may benefit clinically and economically from gastroprotective NSAIDs. Additional research or modeling may provide further insight into the economic implications of managing and preventing NSAID-induced gastroenteropathy.  (+info)

A randomized double-blind placebo-controlled study to assess the effect of oral contraceptive pills on the outcome of medical abortion with mifepristone and misoprostol. (3/308)

This was a randomized double-blind placebo-controlled trial to determine the effect of oral contraceptive (OC) pills taken immediately after medical abortion on the duration of bleeding and complete abortion rate. Two hundred women in the first 49 days of pregnancy were given 200 mg mifepristone orally followed by 400 microg misoprostol vaginally 48 h later. One day later, they were randomized to receive either OC pills (30 microg of ethinyl oestradiol and 0.15 mg of levonorgestrel per tablet) or placebo for 21 days. The complete abortion rates were 98% in the OC group and 99% in the placebo group. The median duration of bleeding was similar: 17 (range: 5-57) days in the OC group and 16 (range: 6-55) days in the placebo group. In the OC group there was a small but significant fall in the haemoglobin concentration by 14 days (5.3 g/dl) after administration of mifepristone. The incidence of side-effects was similar in the two groups. We conclude that the use of OC pills does not decrease the duration of bleeding after medical abortion nor does it affect the abortion rate.  (+info)

Protection against aspirin-induced human gastric mucosal injury by bosentan, a new endothelin-1 receptor antagonist. (4/308)

BACKGROUND: Gastric ulceration induced by aspirin and by non-steroidal anti-inflammatory drugs (NSAIDs) is a major clinical problem. The mechanism of injury is unclear. There is evidence that NSAID-induced injury may cause endothelin activation. Endothelin-induced vasoconstriction has been shown to be capable of causing gastric ulceration. AIM: To investigate whether acute gastroduodenal injury induced in humans by aspirin can be prevented by the endothelin-1 antagonist, bosentan. METHODS: Eighteen healthy volunteers each received 5 x 900 mg aspirin every 12 h on three separate occasions (with either placebo, bosentan 700 mg or misoprostol 400 mg). Treatment order was randomized by Latin square design. Subjects were endoscoped and erosions counted before and 90 min after the first and last dose of aspirin. Plasma concentrations of bosentan were measured up to 5 h post-dose. RESULTS: There was a significant reduction in the mean number of erosions in the aspirin plus bosentan and aspirin plus misoprostol groups after the first dose of aspirin, compared with controls (aspirin plus placebo) (P<0.05). This was not sustained after the fifth dose of aspirin in the aspirin plus placebo and aspirin plus bosentan groups, but was still present in the aspirin plus misoprostol group. The mean plasma concentration of bosentan measured 3.5 h post-dose fell from 4510 (95% CI: 2791-6230) ng/mL after the 1st dose to 2508 (95% CI: 1733-3283) ng/mL after the 5th dose (P = 0.02). CONCLUSION: Endothelin receptor antagonism by bosentan can protect the gastric mucosa against aspirin damage. After five doses, bosentan levels fell, possibly because of enzyme induction, and protection was no longer evident. Further investigation is needed to assess whether higher doses would be effective.  (+info)

Effect of glutamine on the intestinal permeability changes induced by indomethacin in humans. (5/308)

BACKGROUND: Long-term non-steroidal anti-inflammatory drug (NSAID) intake may induce increased intestinal permeability, eventually resulting in enteropathy. Because increased permeability might be related to cell damage resulting from energy depletion, it was hypothesized that glutamine--the major energy source of the intestinal mucosal cell--might prevent permeability changes. METHODS: The 6-h urinary excretion of 51Cr-EDTA after an oral load of 51Cr-EDTA was used in this study as a measure for intestinal permeability. Healthy volunteers underwent a series of permeability tests: (i) basal test; (ii) test following NSAID (indomethacin); (iii) test following NSAID in combination with glutamine and/or misoprostol. RESULTS: The NSAID induced increased permeability in all volunteers. Pre-treatment with glutamine (3x7 g daily, 1 week before NSAID-dosing) did not prevent the NSAID-induced increase in permeability. Multiple doses of glutamine close in time to NSAID-dosing resulted in significantly lower permeability compared to the NSAID without glutamine. Co-administration of misoprostol with the multiple-dose scheme of glutamine resulted in a further reduction in the NSAID-induced increase in permeability. CONCLUSIONS: Glutamine decreases the permeability changes caused by NSAID-dosing when it is administered close in time, and misoprostol has a synergistic effect.  (+info)

Does an acidic medium enhance the efficacy of vaginal misoprostol for pre-abortion cervical priming? (6/308)

Absorption pharmacokinetics reveal a relationship between plasma concentrations of misoprostol and its therapeutic effect. To achieve a constant plasma profile and optimal efficacy, it is important to develop a medium that ensures complete dissolution of vaginal misoprostol tablets. Vaginal misoprostol is said to liquefy better in an acidic medium; thus, the aim of this study was to determine whether a 200 microg misoprostol tablet dissolved in acetic acid would be more efficacious than 200 microg misoprostol dissolved in water for pre-abortion cervical priming. A total of 120 healthy nulliparous women requesting legal termination of pregnancy between 6-12 weeks gestation were allocated randomly to either of the study groups. Vacuum aspiration was performed 3-4 h after insertion of the misoprostol tablet. Using Hegar's dilator, the degree of cervical dilatation before operation was measured. Of 60 women, 14 (23%) achieved a cervical dilatation of >/=8 mm when the misoprostol dose was dissolved in acetic acid; 12 (20%) achieved a similar cervical dilatation when the dose was dissolved in water. The mean cervical dilatation for the acid and water media used was 6.3 mm and 6.2 mm respectively; these differences were not statistically significant, neither were pre-operative and intra-operative blood losses statistically different between the two groups. Twenty-four (40%) and four (7%) respectively of women in whom a water medium was used experienced vaginal bleeding and abdominal pain; 20 (33%) and 0 women respectively among those in whom an acetic acid medium was used experienced vaginal bleeding and abdominal pain. These differences in side effects were not statistically significant. Our study shows that the use of acetic acid to dissolve vaginal misoprostol does not improve the efficacy in achieving successful cervical dilatation for pre-abortion cervical priming.  (+info)

The use of misoprostol for pre-operative cervical dilatation prior to vacuum aspiration: a randomized trial. (7/308)

Misoprostol is effective for cervical priming prior to vacuum aspiration for first trimester termination of pregnancy. Previous studies showed that the oral route was more acceptable to patients but there were higher incidences of side-effects when compared with the vaginal route. This study is to determine the optimal dosage and route of administration of misoprostol for pre-operative cervical dilatation. A double-blind, randomized trial was undertaken for 225 nulliparous women with 8-12 weeks amenorrhoea. They were randomly assigned to groups given 0 (placebo), 200 or 400 microg oral or vaginal misoprostol 3 h prior to vacuum aspiration. In misoprostol-treated groups the baseline cervical dilatation was significantly increased when compared with the placebo group; the effect was dose-related in the oral but not in the vaginal group. The cumulative force and blood loss was significantly decreased in the misoprostol-treated groups. The incidences of side-effects were more frequent in misoprostol groups but were not related to the route and dosage of medication. The duration of procedure, incidences of post-operative complications, the duration of post-operative bleeding and the interval to the first period were similar in the five treatment groups. We conclude that a 3 h pre-treatment interval is effective for both oral and vaginal routes. When given orally, 400 microg is more effective than 200 microg. The efficacy was otherwise similar when compared with the vaginal route. We recommend 400 microg oral misoprostol 3 h prior to vacuum aspiration for cervical dilatation.  (+info)

Cyclooxygenase inhibitors increase Na-K-2Cl cotransporter abundance in thick ascending limb of Henle's loop. (8/308)

Cyclooxygenase inhibitors, such as indomethacin and diclofenac, have well-described effects to enhance renal water reabsorption and urinary concentrating ability. Concentrating ability is regulated in part at the level of the thick ascending limb of Henle's loop, where active NaCl absorption drives the countercurrent multiplication mechanism. We used semiquantitative immunoblotting to test the effects of indomethacin and diclofenac, given over a 48-h period, on the expression levels of the ion transporters responsible for active NaCl transport in the thick ascending limb. Both agents strongly increased the expression level of the apical Na-K-2Cl cotransporter in both outer medulla and cortex. Neither agent significantly altered outer medullary expression levels of other thick ascending limb proteins, namely, the type 3 Na/H exchanger (NHE-3), Tamm-Horsfall protein, or alpha1- or beta1-subunits of the Na-K-ATPase. Administration of the EP3-selective PGE(2) analog, misoprostol, to indomethacin-treated rats reversed the stimulatory effect of indomethacin on Na-K-2Cl cotransporter expression. We conclude that cyclooxygenase inhibitors enhance urinary concentrating ability in part through effects to increase Na-K-2Cl cotransporter expression in the thick ascending limb of Henle's loop. This action is most likely due to elimination of an EP3-receptor-mediated tonic inhibitory effect of PGE(2) on cAMP production.  (+info)