Effects of maternal obesity on the pharmacokinetics of misoprostol during labor induction

Mulheres com obesidade são mais propensas a complicações médicas, cirúrgicas e obstétricas, tais como maiores índices de indução do trabalho de parto e falha na indução. O misoprostol é um análogo sintético da prostaglandina E1 utilizado para a indução do trabalho de parto. O presente trabalho visa avaliar os efeitos da obesidade materna sobre a farmacocinética do misoprostol em parturientes, bem como a avaliação da influência da obesidade na resposta clínica da indução do trabalho de parto. Foram investigadas 40 parturientes, assim distribuídas, Grupo 1: 10 parturientes não obesas, Grupo 2: 10 com obesidade grau 1, Grupo 3: 10 com obesidade grau 2 e Grupo 4: 10 com obesidade grau 3. Após a internação das pacientes, leitura e assinatura do Termo de Consentimento Livre e Esclarecido, foi avaliado o comprimento do colo do útero, o índice de Bishop foi determinado e uma amostra de sangue foi colhida para avaliação dos exames laboratoriais, genótipo e tempo zero da farmacocinética. Após a administração do comprimido de misoprostol 25µg via vaginal, foram colhidas amostras seriadas de sangue nos tempos 15 a 360 minutos. As concentrações plasmáticas do ácido misoprostólico foram analisadas em plasma empregando UPLC-MS/MS. Os parâmetros farmacocinéticos foram calculados com base nas curvas de concentração plasmática total versus tempo empregando o programa Winnonlin. Todas as parturientes realizaram o pré-natal satisfatoriamente e nenhuma havia se submetido a cesárea anterior. As parturientes do grupo 1 apresentaram uma taxa de sucesso de indução de 60%, com uma média de 1,10 dias de indução e 2,50 comprimidos de misoprostol. No grupo 2, houve uma taxa de sucesso de 70%, em 1,40 dias de indução, utilizando 2,80 comprimidos. No grupo 3, a taxa de sucesso foi de 60%, em 1,70 dias de indução e também utilizou 2,80 comprimidos. Entretanto no grupo 4, a taxa de sucesso foi de apenas 30%, em 2,40 dias e utilizando quase o dobro de comprimidos (4,80). Houve uma diferença significativa da falha de indução entre os grupos, a taxa de falha de indução no grupo 4 foi de 70%, enquanto nos demais grupos foi de apenas 10%. O método para análise do ácido misoprostólico em plasma seguiu o preconizado pela legislação vigente, com LIQ de 2,0 pg/mL. Não houve diferença significativa entre os parâmetros farmacocinéticos dos grupos. A AUC variou de 56,77 a 83,89 pg.h/mL; o Cmax de 14,29 a 21,89 pg/mL; o tmaxde 2,25 a 4,5 h; o t1/2 de 0,96 a 1,31 h. Não houve diferença entre o IMC e os parâmetros farmacocinéticos, entretanto houve influência do peso na AUC. Também houve uma relação entre a baixa exposição ao misoprostol (AUC) e maior taxa de falha de indução. Conclui-se que A obesidade influencia a biodisponibilidade (AUC) do fármaco, sugerindo que o regime posológico do misoprostol possa ser alterado. A obesidade também influenciou a taxa de falha de indução, quanto maior o IMC, maior a taxa de falha de indução, maior o tempo de internação, maior o número de comprimidos utilizadosWomen with obesity are more prone to medical, surgical and obstetric complications, such as higher rates of labor induction and failure to induce. Misoprostol is a synthetic analogue of prostaglandin E1 used to induce labor. The present study aims to evaluate the effects of maternal obesity on the pharmacokinetics of misoprostol in parturients, as well as the evaluation of the influence of obesity on the clinical response of labor induction. Group 1: 10 non-obese parturients, Group 2: 10 with obesity grade 1, Group 3: 10 with obesity grade 2 and Group 4: 10 with obesity grade 2. After the patients\' hospitalization, reading and signing of the Informed Consent Term, the length of the cervix was evaluated, the Bishop\'s index was determined and a sample was collected to evaluate the laboratory tests, genotype and time of pharmacokinetics. Following administration of the 25?g misoprostol vaginal tablet, serial blood samples were collected at times of 15 to 360 minutes. Plasma concentrations of misoprostolic acid were analyzed in plasma using UPLC-MS / MS. Pharmacokinetic parameters were calculated based on the total plasma concentration versus time curves using the Winnonlin program. All the parturients performed prenatal satisfactorily and none had undergone previous caesarean section. The parturients of group 1 had an induction success rate of 60%, with a mean of 1.10 days of induction and 2.50 tablets of misoprostol. In group 2, there was a success rate of 70%, at 1.40 days of induction, using 2.80 tablets. In group 3, the success rate was 60% at 1.70 days of induction and also used 2.80 tablets. However, in group 4, the success rate was only 30%, in 2.40 days and using almost twice as many tablets (4.80). There was a significant difference in induction failure between groups, the rate of induction failure in group 4 was 70%, while in the other groups it was only 10%. The method for the analysis of misoprostolic acid in plasma followed the prevailing legislation, with LIQ of 2.0 pg / mL. There was no significant difference between the pharmacokinetic parameters of the groups. AUC ranged from 56.77 to 83.89 pg.h / mL; C max from 14.29 to 21.89 pg / mL; or tmax of 2.25 to 4.5 h; or t1 / 2 from 0.96 to 1.31 h. There was no difference between BMI and pharmacokinetic parameters, however, there was weight influence in AUC. There was also a relationship between low misoprostol exposure (AUC) and higher rate of induction failure. It is concluded that obesity influences the bioavailability (AUC) of the drug, suggesting that the dosage regimen of misoprostol can be altered. Obesity also influenced the rate of induction failure, the higher the BMI, the higher the rate of induction failure, the longer the hospital stay, the greater the number of tablets use

Effects of maternal obesity on the pharmacokinetics of misoprostol during labor induction

Mulheres com obesidade são mais propensas a complicações médicas, cirúrgicas e obstétricas, tais como maiores índices de indução do trabalho de parto e falha na indução. O misoprostol é um análogo sintético da prostaglandina E1 utilizado para a indução do trabalho de parto. O presente trabalho visa avaliar os efeitos da obesidade materna sobre a farmacocinética do misoprostol em parturientes, bem como a avaliação da influência da obesidade na resposta clínica da indução do trabalho de parto. Foram investigadas 40 parturientes, assim distribuídas, Grupo 1: 10 parturientes não obesas, Grupo 2: 10 com obesidade grau 1, Grupo 3: 10 com obesidade grau 2 e Grupo 4: 10 com obesidade grau 3. Após a internação das pacientes, leitura e assinatura do Termo de Consentimento Livre e Esclarecido, foi avaliado o comprimento do colo do útero, o índice de Bishop foi determinado e uma amostra de sangue foi colhida para avaliação dos exames laboratoriais, genótipo e tempo zero da farmacocinética. Após a administração do comprimido de misoprostol 25µg via vaginal, foram colhidas amostras seriadas de sangue nos tempos 15 a 360 minutos. As concentrações plasmáticas do ácido misoprostólico foram analisadas em plasma empregando UPLC-MS/MS. Os parâmetros farmacocinéticos foram calculados com base nas curvas de concentração plasmática total versus tempo empregando o programa Winnonlin. Todas as parturientes realizaram o pré-natal satisfatoriamente e nenhuma havia se submetido a cesárea anterior. As parturientes do grupo 1 apresentaram uma taxa de sucesso de indução de 60%, com uma média de 1,10 dias de indução e 2,50 comprimidos de misoprostol. No grupo 2, houve uma taxa de sucesso de 70%, em 1,40 dias de indução, utilizando 2,80 comprimidos. No grupo 3, a taxa de sucesso foi de 60%, em 1,70 dias de indução e também utilizou 2,80 comprimidos. Entretanto no grupo 4, a taxa de sucesso foi de apenas 30%, em 2,40 dias e utilizando quase o dobro de comprimidos (4,80). Houve uma diferença significativa da falha de indução entre os grupos, a taxa de falha de indução no grupo 4 foi de 70%, enquanto nos demais grupos foi de apenas 10%. O método para análise do ácido misoprostólico em plasma seguiu o preconizado pela legislação vigente, com LIQ de 2,0 pg/mL. Não houve diferença significativa entre os parâmetros farmacocinéticos dos grupos. A AUC variou de 56,77 a 83,89 pg.h/mL; o Cmax de 14,29 a 21,89 pg/mL; o tmaxde 2,25 a 4,5 h; o t1/2 de 0,96 a 1,31 h. Não houve diferença entre o IMC e os parâmetros farmacocinéticos, entretanto houve influência do peso na AUC. Também houve uma relação entre a baixa exposição ao misoprostol (AUC) e maior taxa de falha de indução. Conclui-se que A obesidade influencia a biodisponibilidade (AUC) do fármaco, sugerindo que o regime posológico do misoprostol possa ser alterado. A obesidade também influenciou a taxa de falha de indução, quanto maior o IMC, maior a taxa de falha de indução, maior o tempo de internação, maior o número de comprimidos utilizadosWomen with obesity are more prone to medical, surgical and obstetric complications, such as higher rates of labor induction and failure to induce. Misoprostol is a synthetic analogue of prostaglandin E1 used to induce labor. The present study aims to evaluate the effects of maternal obesity on the pharmacokinetics of misoprostol in parturients, as well as the evaluation of the influence of obesity on the clinical response of labor induction. Group 1: 10 non-obese parturients, Group 2: 10 with obesity grade 1, Group 3: 10 with obesity grade 2 and Group 4: 10 with obesity grade 2. After the patients\' hospitalization, reading and signing of the Informed Consent Term, the length of the cervix was evaluated, the Bishop\'s index was determined and a sample was collected to evaluate the laboratory tests, genotype and time of pharmacokinetics. Following administration of the 25?g misoprostol vaginal tablet, serial blood samples were collected at times of 15 to 360 minutes. Plasma concentrations of misoprostolic acid were analyzed in plasma using UPLC-MS / MS. Pharmacokinetic parameters were calculated based on the total plasma concentration versus time curves using the Winnonlin program. All the parturients performed prenatal satisfactorily and none had undergone previous caesarean section. The parturients of group 1 had an induction success rate of 60%, with a mean of 1.10 days of induction and 2.50 tablets of misoprostol. In group 2, there was a success rate of 70%, at 1.40 days of induction, using 2.80 tablets. In group 3, the success rate was 60% at 1.70 days of induction and also used 2.80 tablets. However, in group 4, the success rate was only 30%, in 2.40 days and using almost twice as many tablets (4.80). There was a significant difference in induction failure between groups, the rate of induction failure in group 4 was 70%, while in the other groups it was only 10%. The method for the analysis of misoprostolic acid in plasma followed the prevailing legislation, with LIQ of 2.0 pg / mL. There was no significant difference between the pharmacokinetic parameters of the groups. AUC ranged from 56.77 to 83.89 pg.h / mL; C max from 14.29 to 21.89 pg / mL; or tmax of 2.25 to 4.5 h; or t1 / 2 from 0.96 to 1.31 h. There was no difference between BMI and pharmacokinetic parameters, however, there was weight influence in AUC. There was also a relationship between low misoprostol exposure (AUC) and higher rate of induction failure. It is concluded that obesity influences the bioavailability (AUC) of the drug, suggesting that the dosage regimen of misoprostol can be altered. Obesity also influenced the rate of induction failure, the higher the BMI, the higher the rate of induction failure, the longer the hospital stay, the greater the number of tablets use

Influence of type 2 diabetes mellitus on pharmacokinetics of nifedipine in hypertensive pregnant women

A nifedipina é uma dihidropiridina, antagonista de canal de cálcio utilizada no tratamento hipertensão arterial na gravidez. O presente estudo visa avaliar a influência do DM2 na farmacocinética da nifedipina em gestantes hipertensas. Foram avaliadas 12 gestantes hipertensas (grupo controle) e 10 gestantes hipertensas portadoras de DM 2 controlado (grupo DM), em uso de nifedipina retard (20 mg, 12/12 horas). A partir da 34ª semana de gestação foram coletadas amostras seriadas de sangue para a análise farmacocinética nos tempos zero, 10, 20, 30, 60, 90, 120, 150, 180, 240, 300, 360, 420, 480, 540, 600, 660 e 720 minutos após a administração do medicamento. Na resolução da gravidez coletou-se sangue materno e fetal para determinar a taxa de transferência placentária da nifedipina. Foram coletadas também alíquotas de sangue do espaço interviloso e de líquido amniótico para a determinação da distribuição do fármaco nestes compartimentos. As concentrações de nifedipina em plasma e líquido amniótico foram analisadas por LC-MS/MS. Os parâmetros farmacocinéticos e de transferência placentária da nifedipina, reportados como mediana foram comparados usando o teste Mann-Whitney, com nível de significância fixado em p<0,05. Os parâmentros encontrados para o grupo controle foram Cmax 26,41 ng/mL; tmax 1,79h; AUC0-12 235,99 ng.h/mL; Kel 0,16 h-1; t1/2 4,34 h; Vd/F 560,96 L; ClT/F 84,77 L/h. Para o grupo DM, foram encontrados os seguintes parâmetros Cmax 23,52 ng/mL; tmax 1,48h; AUC0-12 202,23 ng.h/mL; Kel 0,14 h-1; t1/2 5,00 h; Vd/F 609,40 L; ClT/F 98,94 L/h. As razões da concentração plasmática da nifedipina na veia umbilical, artéria umbilical, espaço interviloso e líquido amniótico pela concentração plasmática na veia materna foram para o grupo controle e para o grupo DM 0,53 e 0,44; 0,46 e 0,33; 0,78 e 0,87, respectivamente, e 0,05 para ambos os grupos. A razão da concentração plasmática da artéria umbilical pela veia umbilical foi 0,82 para o grupo controle e 0,88 para o grupo DM. Não houve influência do DM2 na farmacocinética e transferência placentária da nifedipina em gestantes hipertensas portadoras de diabetes controlado. O estudo sugere que o regime de dose da nifedipina não precisa ser modificado.Nifedipine is a dihydropyridine calcium channel blocker used in the treatment of hypertension in pregnant women. The present study aims to evaluate de effect of T2DM on the pharmacokinetics of nifedipine in hypertensive pregnant women.12 hypertensive pregnant women (control group) and 10 hypertensive pregnant women with controlled T2DM, using nifedipine retard (20 mg, 12/12h) were evaluated. From 34th week of gestation, serial blood samples were collected for pharmacokinetics analysis at times zero, 10, 20, 30, 60, 90, 120, 150, 180, 240, 300, 360, 420, 480, 540, 600, 660 e 720 minutes after drug administration. At delivery, maternal blood, umbilical vein and umbilical artery were collected to determine the rate of placental transfer of nifedipine. Aliquots from placental intervillous space and amniotic fluid were also collected to determine the drug distribution in these compartments. The concentrations of nifedipine in plasma and amniotic fluid were analyzed by LC-MS/MS. Pharmacokinetics and transplacental transfer parameters of nifedipine, reported as median, were compared using Mann-Whitney test, with the level of significance set at p<0.05. The parameters presented for control group were Cmax 26.41 ng/mL; tmax 1.79h; AUC0-12 235.99 ng.h/mL; Kel 0.16 h-1; t1/2 4.34 h; Vd/F 560.96 L; ClT/F 84.77 L/h. For T2DM group the parameters presented were Cmax 23.52 ng/mL; tmax 1.48h; AUC0-12 202.23 ng.h/mL; Kel 0.14 h-1; t1/2 5.00 h; Vd/F 609.40 L; ClT/F 98.94 L/h. The ratios of plasma concentration of nifedipine in umbilical vein, umbilical artery, intervillous space and amniotic fluid for plasma concentration of maternal vein for control group and T2DM group were 0.53 and 0.44; 0.46 and 0.33; 0.78 and 0.87, respectively, and 0.05 for both groups. The ratios of plasma concentration of umbilical artery and umbilical vein were 0.82 for control group and 0.88 for T2DM group. T2DM does not influence the pharmacokinetics of nifedipine in hypertensive pregnant women with controlled diabetes. The study suggests that the nifedipine dose regimen doesnt need to be modified

Analysis of rocuronium in human plasma by liquid chromatography-tandem mass spectrometry with application in clinical pharmacokinetics

Rocuronium (ROC) is a neuromuscular blocking agent used in surgical procedures which is eliminated primarily by biliary excretion. A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for analysis of ROC in human plasma. Separation of ROC and IS (verapamil) was performed using an endcapped C-18 column and a mixture of water:acetonitrile:trifluoracetic acid (50:50:0.1, v/v) as mobile phase. Aliquots of 100 mu L of human plasma were extracted at pH 3, using dichloromethane. The lower limit of quantification of 5 ng/mL shows the high sensitivity of this method. Intra- and inter-assay precision (as relative standard deviation) was all <= 14.2% and accuracy (as relative standard error) did not exceed 10.1%. The validated method was successfully applied to quantify ROC concentrations in patients under surgical procedures up to 6 h after the administration of the 0.4-0.9 mg/kg ROC. The pharmacokinetic parameter estimations of ROC showed AUC/dose of 563 mu g min/mL, total clearance of 2.5 mL/min/kg, volume of distribution at steady state of 190 mL/kg and mean residence time of 83 min. (C) 2013 Elsevier B.V. All rights reserved

Características clínicas e laboratoriais de gestantes com pré-eclâmpsia versus hipertensão gestacional

Purpose: To compare clinical and laboratory characteristics, obstetric and perinatal outcomes of patients with pre-eclampsia versus gestational hypertension. Methods: A retrospective study was carried out to analyze medical records of patients diagnosed with pre-eclampsia and gestational hypertension whose pregnancies were resolved within a period of 5 years, for a total of 419 cases. We collected clinical and laboratory data, obstetric and perinatal outcomes. Comparisons between groups were performed using the test suitable for the variable analyzed: unpaired t test, Mann-Whitney U test or χ2test, with the level of significance set at p<0.05. Results: Were evaluated 199 patients in the gestational hypertension group (GH) and 220 patients in the pre-eclampsia group (PE). Mean body mass index was 34.6 kg/m2 in the GH group and 32.7 kg/m2 in the PE group, with a significant difference between groups. The PE group showed higher systolic and diastolic blood pressure and higher rates of abnormal values in the laboratory tests, although the mean values were within the normal range. Cesarean section was performed in 59.1% of cases of PE and in 47.5% of the GH group; and perinatal outcomes in terms of gestational age and birth weight were significantly lower in the PE group. Conclusion: Women with gestational hypertension exhibit epidemiological characteristics of patients at risk for chronic diseases. Patients with pre-eclampsia present clinical and laboratory parameters of greater severity, higher rates of cesarean delivery and worse maternal and perinatal outcomes.Objetivo: Comparar as características clínicas e laboratoriais, os resultados maternos e perinatais de gestantes com pré-eclâmpsia versushipertensão gestacional. Métodos: Análise retrospectiva dos prontuários médicos de pacientes com diagnóstico de pré-eclâmpsia e hipertensão gestacional, cujas gestações foram resolvidas em um período de cinco anos. Foram coletadas informações laboratoriais, resultados obstétricos e perinatais. As comparações entre os grupos foram realizadas com o uso do teste adequado para a variável analisada: testet não pareado, teste U de Mann-Whitney, ou teste do χ2. Consideramos p<0,05 como nível de significância estatística. Resultados: Foram avaliadas 199 pacientes no grupo com hipertensão gestacional (HG) e 220 pacientes no grupo com pré-eclâmpsia (PE). No grupo HG o índice de massa corpórea médio foi 34,6 kg/m2 e no grupo PE, 32,7 kg/m2, com diferença significativa. O grupo PE apresentou valores de pressão arterial sistólica superiores ao grupo HG. Em relação aos exames laboratoriais, a média de valores denotou, de uma forma geral, maior gravidade no grupo PE. Pacientes submetidas à cesárea foram 59,1% dos casos no grupo PE e 47,5% no grupo HG. Em relação aos resultados perinatais, a idade gestacional e o peso ao nascer foram significativamente inferiores no grupo PE. Cconclusão: As mulheres com hipertensão gestacional apresentam características epidemiológicas de pacientes com risco de doenças crônicas. As pacientes com pré-eclâmpsia apresentam parâmetros clínicos e laboratoriais de maior gravidade, taxas superiores de cesárea e piores resultados maternos e perinatais

Endothelium-dependent vasorelaxant effect of butanolic fraction from Caryocar brasiliense Camb. leaves in rat thoracic aorta

Submitted by Luciana Ferreira ([email protected]) on 2018-08-21T12:09:23Z No. of bitstreams: 2 Artigo - Lais Moraes de Oliveira Porfírio - 2012.pdf: 1716886 bytes, checksum: 886f1bf7e4913f2c97cc0f417c294764 (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5)Approved for entry into archive by Luciana Ferreira ([email protected]) on 2018-08-22T13:09:12Z (GMT) No. of bitstreams: 2 Artigo - Lais Moraes de Oliveira Porfírio - 2012.pdf: 1716886 bytes, checksum: 886f1bf7e4913f2c97cc0f417c294764 (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5)Made available in DSpace on 2018-08-22T13:09:12Z (GMT). No. of bitstreams: 2 Artigo - Lais Moraes de Oliveira Porfírio - 2012.pdf: 1716886 bytes, checksum: 886f1bf7e4913f2c97cc0f417c294764 (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Previous issue date: 2012Caryocar brasiliense Camb. “pequi” is a native plant from the Cerrado region of Brazil that contains bioactive components reported to be antioxidant agents. Previous work has demonstrated that dietary supplementation with pequi decreased the arterial pressure of volunteer athletes. We found that the crude hydroalcoholic extract (CHE) of C. brasiliense leaves relaxed, in a concentration- dependent manner, rat aortic rings precontracted with phenylephrine, and that the butanolic fraction (BF) produced an effect similar to that of the CHE. Aortic relaxation induced by BF was abolished by endothelium removal, by incubation of the nitric oxide synthase inhibitor L-NAME, or the soluble guanylatecyclase inhibitor ODQ. However, incubation with atropine and pyrilamine had no effect on the BF-induced vasorelaxation. Moreover, this effect was not inhibited by indomethacin and tetraethylammonium. The concentration-response curve to calcium in denuded-endothelium rings was not modified after incubation with BF, and the vasorelaxation by BF in endothelium-intact rings precontracted with KCl was abolished after incubation with L-NAME. In addition, administration of BF in anesthetized rats resulted in a reversible hypotension. The results reveal that C. brasiliense possesses both in vivo and in vitro activities and that the vascular effect of BF involves stimulation of the nitric oxide/cyclic GMP pathway

Endothelium-Dependent Vasorelaxant Effect of Butanolic Fraction from Caryocar brasiliense Camb. Leaves in Rat Thoracic Aorta

Caryocar brasiliense Camb. “pequi” is a native plant from the Cerrado region of Brazil that contains bioactive components reported to be antioxidant agents. Previous work has demonstrated that dietary supplementation with pequi decreased the arterial pressure of volunteer athletes. We found that the crude hydroalcoholic extract (CHE) of C. brasiliense leaves relaxed, in a concentration-dependent manner, rat aortic rings precontracted with phenylephrine, and that the butanolic fraction (BF) produced an effect similar to that of the CHE. Aortic relaxation induced by BF was abolished by endothelium removal, by incubation of the nitric oxide synthase inhibitor L-NAME, or the soluble guanylatecyclase inhibitor ODQ. However, incubation with atropine and pyrilamine had no effect on the BF-induced vasorelaxation. Moreover, this effect was not inhibited by indomethacin and tetraethylammonium. The concentration-response curve to calcium in denuded-endothelium rings was not modified after incubation with BF, and the vasorelaxation by BF in endothelium-intact rings precontracted with KCl was abolished after incubation with L-NAME. In addition, administration of BF in anesthetized rats resulted in a reversible hypotension. The results reveal that C. brasiliense possesses both in vivo and in vitro activities and that the vascular effect of BF involves stimulation of the nitric oxide/cyclic GMP pathway

Endothelium-Dependent Vasorelaxant Effect of Butanolic Fraction from Caryocar brasiliense Camb. Leaves in Rat Thoracic Aorta

Caryocar brasiliense Camb. "pequi" is a native plant from the Cerrado region of Brazil that contains bioactive components reported to be antioxidant agents. Previous work has demonstrated that dietary supplementation with pequi decreased the arterial pressure of volunteer athletes. We found that the crude hydroalcoholic extract (CHE) of C. brasiliense leaves relaxed, in a concentration-dependent manner, rat aortic rings precontracted with phenylephrine, and that the butanolic fraction (BF) produced an effect similar to that of the CHE. Aortic relaxation induced by BF was abolished by endothelium removal, by incubation of the nitric oxide synthase inhibitor L-NAME, or the soluble guanylatecyclase inhibitor ODQ. However, incubation with atropine and pyrilamine had no effect on the BF-induced vasorelaxation. Moreover, this effect was not inhibited by indomethacin and tetraethylammonium. The concentration-response curve to calcium in denuded-endothelium rings was not modified after incubation with BF, and the vasorelaxation by BF in endothelium-intact rings precontracted with KCl was abolished after incubation with L-NAME. In addition, administration of BF in anesthetized rats resulted in a reversible hypotension. The results reveal that C. brasiliense possesses both in vivo and in vitro activities and that the vascular effect of BF involves stimulation of the nitric oxide/cyclic GMP pathway