Uso de misoprostol em obstetrícia / Misoprostol use in obstetrics

PONTOS-CHAVE O misoprostol é um análogo da prostaglandina E1 (PGE1) que consta na Lista de Medicamentos Essenciais da Organização Mundial da Saúde (OMS) desde 2005 O Brasil possui uma das regulações mais restritivas do mundo relacionadas ao uso do misoprostol, estabelecendo que o misoprostol tem uso hospitalar exclusivo, com controle especial, e venda, compra e propaganda proibidas por lei Atualmente, o misoprostol é a droga de referência para tratamento medicamentoso nos casos de aborto induzido, tanto no primeiro trimestre gestacional quanto em idades gestacionais mais avançadas O misoprostol é uma medicação efetiva para o preparo cervical e indução do parto O misoprostol é um medicamento essencial para o manejo da hemorragia pós-parto

Pharmacokinetics of vaginal versus buccal misoprostol for labor induction at term.

The IMPROVE study (NCT02408315) compared the efficacy and safety of vaginal and buccal administration of misoprostol for full-term, uncomplicated labor induction. This report compares the pharmacokinetics of misoprostol between vaginal and buccal routes. Women greater than or equal to 14 years of age undergoing induction of labor greater than or equal to 37 weeks gestation without significant complications were randomized to vaginal or buccal misoprostol 25 µg followed by 50 µg doses every 4 h. Misoprostol acid concentrations were determined using liquid chromatography-tandem mass spectrometry for the first 8 h in a subgroup of participants. A population pharmacokinetic model was developed using NONMEM. Plasma concentrations (n = 469) from 47 women were fit to a one-compartment nonlinear clearance model. The absorption rate constant (ka ) was dependent on both route and dose of administration: buccal 25 µg 0.724 (95% confidence interval, 0.54-0.92) h-1 ; 50 µg 0.531 (0.37-0.63) h-1 ; vaginal 25 µg 0.507 (0. 2-1. 4) h-1 ; and 50 µg 0.246 (0.103-0.453) h-1 . Relative bioavailability for vaginal compared to buccal route was 2.4 (1.63-4.77). There was no effect of body mass index or age on apparent clearance 705 (431-1099) L/h or apparent volume of distribution 632 (343-1008) L. The area under the concentration-time curve to 4 h following the first 25 µg dose of misoprostol was 16.5 (15.4-17.5) pg h/ml for buccal and 34.3 (32.5-36.1) pg h/ml for vaginal administration. The rate of buccal absorption was two times faster than that of vaginal, whereas bioavailability of vaginal administration was 2.4 times higher than that of buccal. Decreased time to delivery observed with vaginal dosing may be due to higher exposure to misoprostol acid compared to buccal.

Single-dose pharmacokinetics of orally and rectally administered misoprostol in adult horses.

OBJECTIVE: To characterize the pharmacokinetics of a clinically relevant dose of misoprostol administered PO or per rectum (PR) to horses. ANIMALS: 8 healthy adult horses. PROCEDURES: In a randomized 3-way crossover design, horses received a single dose of misoprostol (5 µg/kg) administered PO (with horses fed and unfed) and PR, with a minimum 3-week washout period separating the experimental conditions. Blood samples were obtained before and at various points after drug administration (total, 24 hours), and plasma concentrations of misoprostol free acid were measured. RESULTS: Mean maximum plasma concentration of misoprostol was significantly higher in the PR condition (mean ± SD, 967 ± 492 pg/mL) and unfed PO condition (655 ± 259 pg/mL) than in the fed PO condition (352 ± 109 pg/mL). Mean area under the concentration-versus-time curve was significantly lower in the PR condition (219 ± 131 pg•h/mL) than in the unfed (1,072 ± 360 pg•h/mL) and fed (518 ± 301 pg•h/mL) PO conditions. Mean time to maximum concentration was ≤ 30 minutes for all conditions. Mean disappearance half-life was shortest in the PR condition (21 ± 29 minutes), compared with values for the unfed (170 ± 129 minutes) and fed (119 ± 51 minutes) PO conditions. No adverse effects were noted. CONCLUSIONS AND CLINICAL RELEVANCE: Misoprostol was rapidly absorbed and eliminated regardless of whether administered PO or PR to horses. Rectal administration may be a viable alternative for horses that cannot receive misoprostol PO, but this route may require more frequent administration to maintain therapeutic drug concentrations.

Pharmacokinetics and ex vivo anti-inflammatory effects of oral misoprostol in horses.

BACKGROUND: Misoprostol is an E prostanoid (EP) 2, 3 and 4 receptor agonist that is anecdotally used to treat and prevent NSAID-induced GI injury in horses. Misoprostol elicits anti-inflammatory effects in vivo in men and rodents, and inhibits TNFα production in equine leucocytes in vitro. OBJECTIVE: Define the pharmacokinetic parameters of oral misoprostol in horses, and determine the inhibitory effect of oral misoprostol administration on equine leucocyte TNFα production in an ex vivo inflammation model. STUDY DESIGN: Pharmacokinetic study, ex vivo experimental study. METHODS: Six healthy adult horses of mixed breeds were used. In phase one, horses were given 5 µg/kg misoprostol orally, and blood was collected at predetermined times for determination of misoprostol free acid (MFA) by UHPLC-MS/MS. Pharmacokinetic parameters were calculated. In phase two, horses were dosed as in phase one, and blood was collected at T0, 0.5, 1 and 4 h following misoprostol administration for leucocyte isolation. Leucocytes were stimulated with 100 ng/mL LPS, and TNFα mRNA concentrations were determined via quantitative real-time PCR. RESULTS: About 5 µg/kg oral misoprostol produced a rapid time to maximum concentration (Tmax ) of 23.4 ± 2.4 min, with a maximum concentration (Cmax ) of 0.29 ± 0.07 ng/mL and area under the curve (AUC0-∞ ) of 0.4 ± 0.12 h ng/mL. LPS stimulation of equine leucocytes ex vivo significantly increased TNFα mRNA concentrations, and there was no significant effect of misoprostol even at the Tmax . MAIN LIMITATIONS: Only a single dose was used, and sample size was small. CONCLUSIONS: Misoprostol is rapidly absorbed following oral administration in horses, and a single 5 µg/kg dose had no significant inhibitory effect on ex vivo LPS-stimulated TNFα mRNA production in leucocytes. Further studies analysing different dosing strategies, including repeat administration or combination with other anti-inflammatory drugs, are warranted.

A crossover pharmacokinetic study of misoprostol by the oral, sublingual and buccal routes.

OBJECTIVES: The aim of the study was to compare the pharmacokinetic parameters of 800 µg oral, sublingual and buccal misoprostol in healthy non-pregnant women. METHODS: This was an open-label, randomised study with a three-way crossover design. Eighteen participants were randomly assigned to treatment sequences of 800 µg oral, sublingual and buccal misoprostol administered under fasting conditions, with a 7-day washout period. Ten participants completed all routes. The primary pharmacokinetic parameters measured were the area under the plasma misoprostol acid concentration-time curve (AUC) from dosing to last quantifiable concentration (AUC0-t), the AUC from 0 to infinity (AUC0-∞) and the maximum plasma concentration (Cmax). Secondary parameters included the plasma elimination rate constant (ke), the half-life and the mean residence time (MRT). RESULTS: There were statistically significant differences in AUC0-∞, AUC0-t and Cmax at the p < 0.05 level for the three routes of administration. The sublingual route achieved the highest bioavailability, and the buccal route achieved the lowest peak concentration. The oral and buccal routes had a similar AUC0-∞ and the buccal route had the highest MRT and ke. There were no differences in half-lives, and no serious adverse events were reported. CONCLUSIONS: This study shows variability in Cmax and AUC by three by-mouth routes of misoprostol administration. The dose in this study was 800 µg, which is among the highest doses seen in current guidelines. These data contribute to the understanding of efficacy and safety of different routes and could provide a basis for deciding whether certain routes are preferable for particular indications.

Aborto farmacológico dispensado a través de un servicio de telemedicina a mujeres de América Latina: complicaciones y su tratamiento / Medical abortion provided by telemedicine to women in Latin America: complications and their treatment

Objetivo: Analizar las complicaciones y los tratamientos declarados después de un aborto farmacológico con mifepristona y misoprostol dispensado a través de un servicio de telemedicina a mujeres que viven en América Latina. Métodos: Estudio observacional basado en el registro de consultas médicas de un servicio de telemedicina. Participaron 872 mujeres que usaron el servicio entre 2010 y 2011. Variables dependientes: total de complicaciones, hemorragia, aborto incompleto, total de tratamientos, evacuación quirúrgica y antibióticos. Variables independientes: edad, zona de residencia, privación socioeconómica, tener hijos/as, embarazos y abortos previos, y semana gestacional. Se ajustaron modelos de Poisson con estimación de la varianza robusta para estimar razones de incidencia (RI) y sus intervalos de confianza del 95% (IC95%). Resultados: El 14,6% de las participantes declaró complicaciones (6,2% hemorragia y 6,8% aborto incompleto). El 19,0% tuvo tratamiento postaborto (10,9% evacuación quirúrgica y 9,3% antibióticos). La privación socioeconómica aumentó en un 64% el riesgo de complicaciones (IC95%: 15%-132%), y dentro de estas un 82% el de aborto incompleto (IC95%: 8%-206%) y un 62% el riesgo de intervención quirúrgica (IC95%: 7%-144%). Los embarazos previos aumentaron el riesgo de hemorragia (RI=2,29; IC95%: 1,33-3,95%). Las mujeres con un embarazo de 12 semanas o más tuvieron un riesgo 2,45 veces mayor de tener tratamiento médico y 2,94 veces mayor de tomar antibióticos, comparado con embarazos de 7 semanas o menos. Conclusión: El aborto farmacológico proveído por telemedicina puede ser una opción segura y efectiva para la interrupción voluntaria del embarazo en contextos donde está legalmente restringido (AU)

Objective: To analyze reported complications and their treatment after a medical abortion with mifepristone and misoprostol provided by a telemedicine service to women living in Latin America. Methods: Observational study based on the registry of consultations in a telemedicine service. A total of 872 women who used the service in 2010 and 2011 participated in the study. The dependent variables were overall complications, hemorrhage, incomplete abortion, overall treatments, surgical evacuation, and antibiotics. Independent variables were age, area of residence, socioeconomic deprivation, previous children, pregnancies and abortions, and week of pregnancy. We fitted Poisson regression models with robust variance to estimate incidence ratios and 95% confidence intervals (95%CI). Results: Complications were reported by 14.6% of the participants: 6.2% reported hemorrhage and 6.8% incomplete abortion. Nearly one-fifth (19.0%) received postabortion treatment: 10.9% had a surgical evacuation and 9.3% took antibiotics. Socioeconomic deprivation increased the risk of complications by 64% (95%CI: 15%-132%), and, among these, the risk of incomplete abortion by 82% (95%CI: 8%-206%) and the risk of surgical intervention by 62% (95%CI: 7%-144%). Previous pregnancies increased the risk of complications and, specifically, the risk of hemorrhage by 2.29 times (95%CI: 1.33-3.95%). Women with a pregnancy of 12 or more weeks had a 2.45 times higher risk of receiving medical treatment and a 2.94 times higher risk of taking antibiotics compared with women with pregnancies of 7 or less weeks. Conclusion: Medical abortion provided by telemedicine seems to be a safe and effective alternative in contexts where it is legally restricted (AU)

[Pharmacology of misoprostol (pharmacokinetic data, adverse effects and teratogenic effects)]. / Pharmacologie du misoprostol (données pharmacocinétiques, tolérance et effets tératogènes).

Misoprostol is a synthetic analogue of prostaglandin E1. It is used in gynaecology because of its properties of myometrium smooth muscle cells contraction and its effects on the cervix. Misoprostol oral bioavailability is low and several authors have assessed whether the administration by other routes increased its pharmacodynamic effects. This paper summarizes the pharmacokinetic studies after other routes of administration: vaginal, sublingual, buccal or rectal. It also provides an update on its adverse effects and teratogenic effects.

Bioequivalence of two misoprostol tablets in healthy Chinese female volunteers: a single-dose, two-period, double crossover study.

OBJECTIVE: To assess the bioequivalence of a new generic formulation of misoprostol (CAS 59122-46-2) 0.2 mg tablets (test) and the available branded tablet (reference) for the requirement of state regulatory criteria and the marketing of the test product in China. METHODS: A randomized-sequence, 2-period crossover study was conducted in 20 healthy Chinese female volunteers in the fasted state. Blood samples were collected at baseline and 0.083, 0.17, 0.25, 0.33, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4 and 6 h after a single oral dose of 0.6 mg misoprostol test or reference, followed by a 7-day washout period. Misoprostol acid, the active metabolite of misoprostol, was determined by an HPLC-MS/MS method. Drug And Statistics 2.0 was used to calculate the pharmacokinetics parameters and assess bioequivalence of the 2 formulations. It was considered bioequivalent if the 90% CIs of the mean ratios (test: reference) for Tmax, Cmax and AUC0-t were all within the range from 80% to 125%. Adverse events were monitored throughout the study based on clinical parameters and patient reports. RESULTS: The main pharmacokinetics parameters for the test and reference were as follows: t1/2 was (0.680 ± 0.371) h and (0.650 ± 0.264) h; Tmax was (0.415 ± 0.087) h and (0.399 ± 0.097) h; Cmax was (1.941 ± 0.417) ng/mL and (2.047 ± 0.397) ng/mL; AUC0-t was (1.535 ± 0.419) ng·h/mL and (1.652 ± 0.400)ng·h/mL, and the AUC0-∞ was (1.576 ± 0.465) ng·h/mL and (1.686 ± 0.396) ng·h/mL. The mean ratios (test: reference) for Cmax, AUC0-t, and AUC0-∞ were 95.3% ±13.2%, 92.65% ± 17.31%, and 93.61%±18.97%, respectively. No significant (p>0.05) differences in pharmacokinetic parameters were found between preparations, treatments and periods. CONCLUSIONS: This single-dose study in healthy Chinese fasted volunteers was shown that the misoprostol test and reference met the requirement of US and China regulatory criterion, and the test and reference were bioequivalent.

Effect of bacterial vaginosis on the pharmacokinetics of misoprostol in early pregnancy.

BACKGROUND: Misoprostol has been shown to be an effective agent for cervical ripening and termination of early pregnancy especially when administered vaginally. Our objective was to evaluate whether bacterial vaginosis (BV) affected the pharmacokinetics of vaginally administered misoprostol during early pregnancy. METHODS: Ten women with BV and 10 healthy women requesting medical abortion up to 9 weeks of pregnancy were administered 200 mg mifepristone followed 24-48 h later by a single dose of 800 µg misoprostol vaginally. Blood samples were taken before (0 h) and 0.5, 1, 2, 3 and 4 h after misoprostol administration. Misoprostol acid was determined in serum samples using liquid chromatography/tandem mass spectrometry. RESULTS: All women with BV had a vaginal pH > 4.7. The mean bioavailability measured as the area under the curve (AUC) and maximum concentration (C(max)) appeared higher in the control than in the BV group (1458.7 versus 878.1 pg h/ml) and (630.7 versus 342.5 pg/ml), respectively, but did not achieve statistical significance and there was no other significant difference in the pharmacokinetics between the two groups. However, if two women with vaginal pH > 4.7 were excluded from the control group the difference in AUC240 (1359 versus 878.1 pgh/ml) reached statistical significance (P = 0.048). CONCLUSIONS: BV had an effect on pharmacokinetics of vaginally administered misoprostol in early pregnancy. However, the results should be interpreted with caution due to the small sample size and marked individual variations.

[Developmental toxicity of misoprostol: an update]. / Toxicidad del misoprostol sobre la gestación: Revisión de la literatura.

Misoprostol, a synthetic analog of prostaglandin E1, is currently used in Chile and other countries as an antiulcer medication, mainly for the prevention of non-steroidal anti-inflammatory-induced gastric ulcers. Due to its uterotonic properties, it is also indicated in obstetrics for induction of labor and termination of pregnancy. In this last case, misoprostol is either used alone or in combination with other oxytocic drugs such as methotrexate or mifepristone. The use of misoprostol as an abortifacient agent is considered to be safe since it rarely causes serious side effects. However up to 15 % of misoprostol-induced-abortions may not be successful, even under medical supervision, leading to in utero exposure to the drug and to the induction of a series of birth defects including limb and joints defects and Moebius syndrome. Reports from the nineties failed to show a strong epidemiological association between in utero drug exposure and induction of defects, a situation that has changed now that the number of cases reported has increased. Since the practice of abortion is illegal in Chile, many women turn to off-medical procedures to interrupt their pregnancy and use misoprostol as an easy and cheap alternative, readily available in the INTERNET. The lack of medical supervision in these cases may lead to situations that favor the induction of congenital defects. Here, we present an updated review of scientific data, to evaluate the risk of birth defects in babies exposed to the drug during pregnancy termination failed attempts.

A randomized comparison of pharmacokinetics of a single vaginal dose of dry misoprostol or misoprostol moistened with normal saline or with acetic acid.

BACKGROUND: The pharmacokinetics of vaginal misoprostol as a dry tablet or as a tablet moistened with normal saline or with acetic acid were studied. METHODS: For this study, 42 women requesting termination of pregnancy at gestational age of <12 weeks were recruited and received 400 µg vaginal misoprostol tablets. They were randomized into three groups: (i) dry tablets, (ii) tablets moistened with 3 ml of normal saline and (iii) tablets moistened with 3 ml of 5% acetic acid. Venous blood samples were taken at 0, 15, 30, 45, 60, 90, 120, 150, 180, 210, 240, 270, 300, 330 and 360 min after misoprostol administration. Misoprostol acid (MPA) was determined in serum samples using gas chromatography/tandem mass spectrometry. RESULTS: The serum peak MPA concentration (C(max)) was significantly higher and the time-to-peak concentration (T(max)) was significantly shorter in the normal saline and acetic acid groups, when compared with the dry tablet group. Both areas under the curve at 240 and 360 min (AUC(240) and AUC(360)) of the normal saline and acetic acid groups were also significantly greater than that of the dry tablet group. The coefficients of variation in C(max) and T(max) were highest in the normal saline group, while that of AUC(240) and AUC(360) were highest in the dry tablet group. The C(max) was significantly higher in subjects in the dry tablet group with vaginal pH < 5 than in those with pH 5. There were no significant differences in other pharmacokinetic parameters between subjects with vaginal pH < 5 and those with vaginal pH 5 in all three groups. CONCLUSIONS: Vaginal misoprostol tablets moistened with normal saline or 5% acetic acid achieved better absorption than the dry tablet. The use of vaginal misoprostol tablets moistened with normal saline or 5% acetic acid would potentially improve the clinical efficacy of misoprostol. HKClinicalTrials.com registration: HKCTR-821.

Development and validation of highly sensitive method for determination of misoprostol free acid in human plasma by liquid chromatography-electrospray ionization tandem mass spectrometry: application to a clinical pharmacokinetic study.

A highly sensitive, selective and evaporation free SPE extraction, ESI-LC-MS/MS method has been developed for estimation of misoprostol free acid in human plasma using misoprostol acid-d(5) as an internal standard (IS). The analyte was separated using isocratic mobile phase on reverse phase column and analyzed by MS/MS in the multiple reaction monitoring mode using the respective [M-H] anions, m/z 367-249 for misoprostol acid and m/z 372-249 for the IS. The total run time was 5.0 min and the elution of misoprostol acid and misoprostol acid-d(5) (IS) occurred at 3.6 min. The developed method was validated in human plasma with a lower limit of quantification of 2.5 pg/mL. A linear response function was established for the range of concentrations 2.5-1200 pg/mL (r>0.998) for misoprostol acid in human plasma. The intra and inter-day precision values for misoprostol acid met the acceptance as per FDA guidelines. Misoprostol acid was stable in the battery of stability studies viz., bench-top, auto-sampler and freeze/thaw cycles. The developed assay method was applied to an oral pharmacokinetic study in humans.

Comparison of sublingual versus vaginal misoprostol for second-trimester pregnancy termination: a meta-analysis.

BACKGROUND: The development of safe and effective techniques for second-trimester abortion (associated or not with fetal death) has become a major clinical challenge. AIMS: To compare the efficacy and safety of sublingual versus vaginal misoprostol for mid-trimester pregnancy termination. METHODS: We conducted a meta-analysis of published randomised controlled trials that compared sublingual and vaginal routes. Primary outcome measures were complete abortion rate at 24 and 48 h and induction-abortion interval, and the secondary outcome measures were side effects and patients' preference for the route. Pooled risk ratios were calculated for categorical variables, and continuous variables were compared by means of weighted mean differences. RESULTS: Both routes' efficacy was similar following 24 h of treatment (pooled RR 1.04, 95% CI 0.93-1.7). Successful induction percentage after 24 h was significantly higher in nulliparous women with vaginal misoprostol (pooled RR 0.78; 95% CI 0.71-0.87). The efficacy after 48 h was significantly greater with vaginal misoprostol in the general population (pooled RR 0.96; 95% CI 0.93-0.99) and in nulliparous women (pooled RR 0.89; 95% CI 0.86-0.95). The sublingual route shortened the induction-fetal expulsion interval (WMD -4.54, 95% CI -8.03 to -1.05) and was the route preferred among women. No statistically significant differences between treatment groups were observed for placental retention or for any side effect except for fever, which was more common in the vaginal group. CONCLUSIONS: Sublingual and vaginal misoprostol are safe and effective for mid-trimester pregnancy termination. The differences obtained between both routes probably do not have clinical consequences.

Toxicidad del misoprostol sobre la gestación: Revisión de la literatura / Developmental toxicity of misoprostol: An update

Misoprostol, a synthetic analog of prostaglandin E1, is currently used in Chile and other countries as an antiulcer medication, mainly for the prevention of non-steroidal anti-infammatory-induced gastric ulcers. Due to its uterotonic properties, it is also indicated in obstetrics for induction of labor and termination of pregnancy. In this last case, misoprostol is either used alone or in combination with other oxytocic drugs such as methotrexate or mifepristone. The use of misoprostol as an abortifacient agent is considered to be safe since it rarely causes serious side effects. However up to 15 percent of misoprostol-induced-abortions may not be successful, even under medical supervision, leading to in utero exposure to the drug and to the induction of a series of birth defects including limb and joints defects and Moebius syndrome. Reports from the nineties failed to show a strong epidemiological association between in utero drug exposure and induction of defects, a situation that has changed now that the number of cases reported has increased. Since the practice of abortion is illegal in Chile, many women turn to off-medical procedures to interrupt their pregnancy and use misoprostol as an easy and cheap alternative, readily available in the INTERNET. The lack of medical supervision in these cases may lead to situations that favor the induction of congenital defects. Here, we present an updated review of scientifc data, to evaluate the risk of birth defects in babies exposed to the drug during pregnancy termination failed attempts.

Eficácia de dinoprostone e misoprostol para indução do trabalho de parto em nulíparas / Efficacy of dinoprostone and misoprostol for labor induction in nulliparous women

OBJETIVO: verificar a eficácia e a segurança de dinoprostone e misoprostol para indução do parto vaginal, com ou sem o uso de ocitocina em nulíparas. MÉTODOS: realizou-se estudo retrospectivo, observacional, envolvendo 238 pacientes que foram submetidas à indução do parto de janeiro de 2008 a fevereiro de 2010 com uso de misoprostol 25 mcg via vaginal ou pessário contendo 10 mg de dinoprostone. Desse grupo, foram selecionadas 184 pacientes, que apresentavam as seguintes características: nulíparas, gestação entre 37 e 42 semanas, feto único, apresentação cefálica, membranas íntegras e índice de Bishop < 3. Os resultados obstétricos e neonatais foram analisados e comparados entre ambos os grupos. A análise estatística foi realizada com o teste t, Chi quadrado e exato de Fisher, adotando-se como nível de significância valores p<0,05. RESULTADOS: a taxa de parto vaginal não foi estatisticamente diferente em pacientes que utilizaram misoprostol e dinoprostone (43,2 versus 50 por cento, p=0,35), respectivamente. O amadurecimento do colo foi superior no grupo com misoprostol (87,3 versus 75,6 por cento, p=0,04). Foi necessária a utilização da ocitocina em 58,8 por cento no grupo com misoprostol e 57,3 por cento no grupo com dinoprostone após o amadurecimento do colo. Falha de indução foi a principal indicação do parto cesárea em ambos os grupos, sem diferença estatística significante. Eventos adversos maternos e fetais, como taquissistolia e índices de Apgar foram similares. CONCLUSÃO: dinoprostone e misoprostol são eficazes para indução do parto vaginal, embora seja necessária a associação com ocitocina, apresentando perfil de segurança semelhante, sendo misoprostol mais eficiente no amadurecimento do colo uterino.

PURPOSE: to determine the efficacy and safety of dinoprostone and misoprostol for the induction of vaginal childbirth, with or without the use of oxytocin in nulliparous women. METHODS: in this retrospective observational study, 238 patients were subjected to the induction of delivery from January 2008 to February 2010 with the use of misoprostol 25 mcg by the vaginal route or a pessary containing 10 mg of dinoprostone. A total of 184 patients were selected, with the following characteristics: nulliparous, gestational age of 37-42 weeks, singleton pregnancies, cephalic presentation, intact membranes, and Bishop score < 3. Obstetric and neonatal data were analyzed and compared between groups. The Student t-test, chi-square test and Fisher's exact test were used for statistical analysis, with the level of significance set at p<0.05. RESULTS: the rate of vaginal childbirth did not differ significantly in patients who used misoprostol and dinoprostone (43.2 percent versus 50 percent; p = 0.35, respectively). The ripening of cervix was higher in the group treated with misoprostol (87.3 percent versus 75.6 percent, p=0.04). The use of oxytocin was necessary in 58.8 percent of the misoprostol group and 57.3 percent in the dinoprostone group after the ripening of cervix. Failed induction was the primary indication of caesarean section delivery in both groups, with no significant difference between them. Fetal and maternal adverse events, such as tachysystole and Apgar scores were similar. CONCLUSION: dinoprostone and misoprostol are both effective for vaginal childbirth induction, although they need to be combined with oxytocin. They showed a similar safety profile, with misoprostol being more efficient regarding cervical ripening.

Mononitrato de isosorbide o misoprostol en maduración cervical en embarazos interrumpidos durante el primer trimestre / Isosorbide mononitrate or misoprostol for cervical ripening in missed pregnacies during first trimester

Objetivo Comparar los efectos del mononitrato de isosorbide o el misoprostol en la maduración cervical en embarazos interrumpidos durante el primer trimestre. Método Las pacientes se asignaron al azar para recibir 40mg de mononitrato de isosorbide (grupo A) o 200μg de misoprostol (grupo B) por vía vaginal. Se evaluó la tasa de eficacia, tiempo entre el inicio del tratamiento y la maduración cervical y presencia de efectos adversos. Resultados No se encontraron diferencias estadísticamente significativas entre las características generales de las pacientes de ambos grupos (p=ns). El tiempo entre el inicio del tratamiento y la maduración cervical fue más corto en las pacientes del grupo B que en las pacientes del grupo A, pero esta diferencia no fue estadísticamente significativa (p=ns). Además, se observó un porcentaje similar de pacientes tratadas con mononitrato de isosorbide y con misoprostol que expulsó exitosamente en las primeras 24h de tratamiento (p=ns). Las pacientes del grupo A presentaron una alta frecuencia de cefalea al compararlo con las pacientes del grupo B (p<0,05).Conclusión El mononitrato de isosorbide tiene efectos similares al misoprostol en la maduración cervical en embarazos interrumpidos durante el primer trimestre, pero la frecuencia de cefalea fue significativamente mayor en este grupo de pacientes (AU)

Objective To compare the effects of isosorbide mononitrate and misoprostol for cervical ripening in interrupted pregnancies during the first trimester. Methods Patients were randomly assigned to receive 40mg of isosorbide mononitrate (group A) or 200mcg of misoprostol (group B) vaginally. The efficacy rate, time between treatment start and cervical ripening, and adverse effects were evaluated.ResultsThere were no statistically significant differences in the general characteristics between the two groups (p=ns). The time between treatment start and cervical ripening was shorter in group B than in group A, but this difference was not significant (p=ns). The percentage of patients with a successfully ripened cervix within 24h of treatment was similar in the two groups (p=ns). The frequency of patients with headache was higher in group A than in group B (p<0.05).Conclusion Isosorbide mononitrate has similar effects to misoprostol in cervical ripening in interrupted pregnancies during the first trimester but the frequency of headache is significantly higher in patients receiving isosorbide mononitrate (AU)

Clinical use of misoprostol in nonpregnant women: review article.

Misoprostol, a prostaglandin E1 derivative, has been widely used in nonpregnant women because of its cervical ripening and uterotonic effects. A large number of studies have demonstrated its effectiveness in enhancing ease of cervical dilation. This review article describes its pharmacokinetic profile and the relationship between prostaglandins and cervical ripening and uterine contraction and provides a review of the clinical use of misoprostol in nonpregnant women including cervical priming before hysteroscopy, before insertion of an intrauterine device, in endometrium biopsy, preoperatively in myomectomy, and before intrauterine insemination to improve pregnancy rates. Adverse effects are also described.

Medical and surgical options for induced abortion in first trimester.

Medical abortion has been shown to be an effective alternative to surgery for termination of pregnancy in the late as well as the early first trimester of pregnancy. This review discusses the development, application and the current issues with medical and surgical abortion in the first trimester. Studies comparing the two approaches are also assessed as well as potential research directions in this area.