Effect of co-administration of BRL-37344 and tadalafil on reduction of overactive bladder symptoms after induction of detrusor overactivity in mice

Abstract Purpose: To evaluate the impact of the combination of BRL 37344 and tadalafil (TDF) on the reduction of overactive bladder (OB) symptoms. Methods: Thirty mice were randomized into 5 groups (G) of 6 animals each. L-NAME was used to induce DO. G1: Control; G2: L-NAME; G3: L-NAME + TDF; G4: L-NAME + BRL 37344; G5: L-NAME + TDF + BRL 37344. After 30 days of treatment, the animals were submitted to cystometry to evaluate non-voiding contractions (NVC), threshold pressure (TP), baseline pressure (BP), frequency of micturition (FM) and threshold volume (TV). Differences between the groups were analyzed with ANOVA followed by the Tukey test. Results: NVC increased in G2 (4.33±2.58) in relation to G1 (1.50±0.55). NVC decreased in G3 (2.00±1.10), G4 (1.50±1.52) and G5 (2.00±1.26) compared to G2 (p<0.05). FM decreased in G3 (0.97±0.71), G4 (0.92±0.38) and G5 (1.05±0.44) compared to G2 (p<0.05). However, the combination of TDF and BRL37344 was not more effective at increasing NVC and improving FM than either drug alone. The five groups did not differ significantly with regard to TV. Conclusion: The combination of BRL 37344 and TDF produced no measurable additive effect on reduction of OB symptoms.

Efficacy and safety of the single-capsule combination of fluticasone/formoterol in patients with persistent asthma: a non-inferiority trial / Eficácia e segurança da associação fluticasona/formoterol em cápsula única em pacientes com asma persistente: estudo de não inferioridade

OBJECTIVE: Fluticasone and formoterol are effective in the treatment of asthma. When a corticosteroid alone fails to control asthma, combination therapy is the treatment of choice. The objective of this study was to compare the efficacy and safety of formulations containing budesonide/formoterol (BUD/FOR), fluticasone alone (FLU), and the single-capsule combination of fluticasone/formoterol (FLU/FOR) on lung function in patients with mild-to-moderate persistent asthma. METHODS: This was a randomized, multicenter, open phase III trial conducted in Brazil. The primary efficacy analysis was the assessment of non-inferiority between FLU/FOR and BUD/FOR combinations regarding FEV1 (in L) at the final visit. The secondary analyses were PEF, level of asthma control, serum cortisol levels, frequency of adverse events, adherence to treatment, and appropriate inhaler use. RESULTS: We randomized 243 patients to three groups: FLU/FOR (n = 79), BUD/FOR (n = 83), and FLU (n = 81). In terms of the mean FEV1 after 12 weeks of treatment, the difference between the FLU/FOR and BUD/FOR groups was 0.22 L (95% CI: −0.06 to 0.49), whereas the difference between the FLU/FOR and FLU groups was 0.26 L (95% CI: −0.002 to 0.52). Non-inferiority was demonstrated by the difference between the lower limits of the two 95% CIs (−0.06 vs. −0.002). The level of asthma control and PEF were significantly greater in the FLU/FOR and BUD/FOR groups than in the FLU group. There were no significant differences among the groups regarding patient adherence, patient inhaler use, or safety profile of the formulations. CONCLUSIONS: The single-capsule combination of FLU/FOR showed non-inferiority to the BUD/FOR and FLU formulations regarding efficacy and ...

OBJETIVO: A fluticasona e o formoterol são efetivos no tratamento da asma. A terapia combinada é o tratamento de escolha quando o corticosteroide isolado não controla a asma. O objetivo deste estudo foi comparar a eficácia e segurança de formulações contendo budesonida/formoterol (BUD/FOR), fluticasona (FLU) e fluticasona/formoterol (FLU/FOR) em cápsula única sobre a função pulmonar em pacientes com asma persistente leve e moderada. MÉTODOS: Estudo de fase III multicêntrico brasileiro, aleatorizado e aberto. A análise primária de eficácia foi a avaliação de não inferioridade da combinação FLU/FOR perante a combinação BUD/FOR em relação ao VEF1 (em L) na visita final. As análises secundárias foram PFE, nível de controle da asma, nível de cortisol sérico, frequência de eventos adversos, aderência ao tratamento e uso adequado do inalador. RESULTADOS: Foram randomizados 243 pacientes nos grupos FLU/FOR (n = 79), BUD/FOR (n = 83) e FLU (n = 81). Após 12 semanas de tratamento, a média da diferença do VEF1 foi de 0,22 L (IC95%: −0,06 a 0,49) entre os grupos FLU/FOR e BUD/FOR e de 0,26 L (IC95%: −0,002 a 0,52) entre os grupos FLU/FOR e FLU. A não inferioridade ficou demonstrada pela diferença de limite inferior do IC95% (−0,06 vs. −0,002). O nível de controle da asma e o PFE foram significativamente maiores nos grupos FLU/FOR e BUD/FOR em comparação com o grupo FLU. Não houve diferenças significativas em relação a adesão, uso do inalador e perfil de segurança entre os grupos. CONCLUSÕES: ...

Equivalência farmacêutica da formulação combinada de budesonida e formoterol em cápsula única com dispositivo inalador de pó / Pharmaceutical equivalence of the combination formulation of budesonide and formoterol in a single capsule with a dry powder inhaler

OBJETIVO: Avaliar a equivalência farmacêutica da formulação teste (associação fixa de budesonida e fumarato de formoterol em cápsula única dispensada com o dispositivo Aerocaps®) em relação a uma formulação referência (budesonida e fumarato de formoterol em duas cápsulas distintas dispensadas com o dispositivo Aerolizer®). MÉTODOS: Estudo in vitro no qual foram realizadas identificação/quantificação dos ingredientes ativos por HPCL e determinação da uniformidade da dose liberada e da distribuição aerodinâmica das partículas das formulações teste e referência. RESULTADOS: Na formulação teste, o teor de budesonida e de formoterol foi de 111,0% e 103,8%, respectivamente, enquanto esse foi de 110,5% e 104,5% na formulação referência. Na formulação teste, a uniformidade das doses de budesonida e de formoterol foi de 293,2 µg e 10,2 µg, respectivamente, enquanto essa foi de 353,0 µg e 11,1 µg na formulação referência. Esses resultados estão dentro da faixa recomendada para esse tipo de formulação (75-125% da dose rotulada). A fração de partículas finas (< 5 µm) para budesonida e formoterol foi de, respectivamente, 45% e 56% na formulação teste e de 54% e 52% na formulação referência. CONCLUSÕES: As formulações teste e referência apresentaram níveis de ingredientes ativos, uniformidade de doses e diâmetros aerodinâmicos apropriados ao uso com seus respectivos dispositivos inalatórios de pó.

OBJECTIVE: To evaluate the pharmaceutical equivalence of a test formulation (fixed-dose combination of budesonide and formoterol fumarate in a single capsule dispensed in an Aerocaps® inhaler) in relation to a reference formulation (budesonide and formoterol fumarate in two separate capsules dispensed in an Aerolizer® inhaler). METHODS: This was an in vitro study in which we performed the identification/quantification of the active ingredients by HPLC and determined dose uniformity and aerodynamic particle size distribution in the test and reference formulations. RESULTS: In the test formulation, the content of budesonide and formoterol was 111.0% and 103.8%, respectively, compared with 110.5% and 104.5%, respectively, in the reference formulation. In the test formulation, dose uniformity regarding budesonide and formoterol was 293.2 µg and 10.2 µg, respectively, whereas it was 353.0 µg and 11.1 µg in the reference formulation. These values are within the recommended range for this type of formulation (75-125% of the labeled dose). The fine particle fraction (< 5 µm) for budesonide and formoterol was 45% and 56%, respectively, in the test formulation and 54% and 52%, respectively, in the reference formulation. CONCLUSIONS: For both of the formulations tested, the levels of active ingredients, dose uniformity, and aerodynamic diameters were suitable for use with the respective dry powder inhalers.

Artesunate + amodiaquine versus artemether-lumefantrine for the treatment of uncomplicated Plasmodium falciparum malaria in the Colombian Pacific region: a noninferiority trial / Artesunato + amodiaquina versus artemether-limefantrina para o tratamento da malaria não complicada por Plamodium falciparum no Pacifico Colombiano: um estudo de não inferioridade

INTRODUCTION: In Colombia, there are no published studies for the treatment of uncomplicated Plasmodium falciparum malaria comparing artemisinin combination therapies. Hence, it is intended to demonstrate the non-inferior efficacy/safety profiles of artesunate + amodiaquine versus artemether-lumefantrine treatments. METHODS: A randomized, controlled, open-label, noninferiority (Δ≤5%) clinical trial was performed in adults with uncomplicated P. falciparum malaria using the 28‑day World Health Organization validated design/definitions. Patients were randomized 1:1 to either oral artesunate + amodiaquine or artemether-lumefantrine. The primary efficacy endpoint: adequate clinical and parasitological response; secondary endpoints: - treatment failures defined per the World Health Organization. Safety: assessed through adverse events. RESULTS: A total of 105 patients was included in each group: zero censored observations. Mean (95%CI - Confidence interval) adequate clinical and parasitological response rates: 100% for artesunate + amodiaquine and 99% for artemether-lumefantrine; the noninferiority criteria was met (Δ=1.7%). There was one late parasitological therapeutic failure (1%; artemether-lumefantrine group), typified by polymerase chain reaction as the MAD20 MSP1 allele. The fever clearance time (artesunate + amodiaquine group) was significantly shorter (p=0.002). Respectively, abdominal pain for artesunate + amodiaquine and artemether-lumefantrine was 1.9% and 3.8% at baseline (p=0.68) and 1% and 13.3% after treatment (p<0.001). CONCLUSIONS: Uncomplicated P. falciparum malaria treatment with artesunate + amodiaquine is noninferior to the artemether-lumefantrine standard treatment. The efficacy/safety profiles grant further studies in this and similar populations.

INTRODUÇÃO: Na Colômbia não existem estudos publicados sobre o tratamento da malária não complicada por Plasmodium falciparum comparando as terapias combinadas com artemisinina. Destarte, quer se demonstrar a não inferioridade dos perfis de eficácia/segurança dos tratamentos com artesunato+amodiaquina versus artemeter-lumefantrina. MÉTODOS: Foi realizado um estudo clínico de não inferioridade (∆≤5%), aleatório, controlado, aberto, em adultos com malária não complicada por P. falciparum usando o desenho validado de 28 dias e os desenhos validados/definidos pela Organização Mundial da Saúde. Os pacientes foram aleatorizados (1:1) para ambos artesunato+amodiaquina ou artemeter-lumefantrina orais. Critérios primários de eficácia: resposta clínica e parasitológica adequada; Criterios de eficácia secundários: as falhas de tratamento definidos pela Organização Mundial da Saúde. A segurança: avaliada através de eventos adversos. RESULTADOS: Foram incursos 105 pacientes em cada grupo: zero observações censuradas. As taxas médias da resposta clínica e parasitológica adequada (95% IC - intervalo de confiança): 100% para artesunato+amodiaquina e 99% para artemeter-lumefantrina; atingiu-se o critério de não inferioridade (∆=1.7%). Houve uma falha terapêutica parasitológica tardia (1%; grupo artemeter-lumefantrina), caracterizada mediante reação em cadeia da polimerase como o alelo MAD20 MSP1. Tempo de remissão da febre (grupo artesunato+amodiaquina), foi significativamente mais curto (p=0.002). Dor abdominal, para artesunato+amodiaquina e artemeter-lumefantrina, respectivamente, 1.9% e 3.8% (p=0.68) na linha de base, 1% e 13.3% pós-tratamento (p<0.001). CONCLUSÕES: O tratamento com artesunato+amodiaquina da malária não complicada por P. falciparum é não inferior ao tratamento normal com artemeter-lumefantrina. Os perfis de eficácia/segurança justificam estudos adicionais nesta e outras populações semelhantes.

Avaliação da eficácia e segurança da associação de budesonida e formoterol em dose fixa e cápsula única no tratamento de asma não controlada: ensaio clínico randomizado, duplo-cego, multicêntrico e controlado / Evaluation of the efficacy and safety of a fixed-dose, single-capsule budesonide-formoterol combination in uncontrolled asthma: a randomized, double-blind, multicenter, controlled clinical trial

OBJETIVO: Avaliar a eficácia e a segurança da associação de budesonida e formoterol em dose fixa e cápsula única, em comparação ao uso de budesonida isolada em pacientes com asma não controlada. MÉTODOS: Ensaio clínico randomizado, duplo-cego, multicêntrico, de fase III, com grupos paralelos, comparando a eficácia de curto prazo e a segurança da formulação em pó de budesonida (400 µg) e formoterol (12 µg) com a formulação em pó de budesonida (400 µg) em 181 participantes com asma não totalmente controlada. A idade dos participantes variou de 18-77 anos. Após um período de run-in de 4 semanas, durante o qual todos os participantes receberam budesonida duas vezes por dia, houve a randomização para um dos tratamentos do estudo. O tratamento foi administrado duas vezes ao dia por 12 semanas. Os principais desfechos foram VEF1, CVF e PFE matinal. Os dados foram analisados por intenção de tratar. RESULTADOS: O grupo tratado com a associação, quando comparado ao grupo budesonida isolado, teve uma melhora significativa no VEF1 (0,12 L vs. 0,02 L; p = 0.0129) e no PFE matinal (30,2 L/min vs. 6,3 L/min; p = 0,0004). Esses efeitos foram acompanhados por boa tolerabilidade e segurança, como demonstrado pela baixa frequência de eventos adversos menores. CONCLUSÕES: A associação em cápsula única de budesonida e formoterol mostrou ser eficaz e segura. Os resultados demonstram que essa formulação é uma opção terapêutica válida para a obtenção e manutenção do controle da asma.

OBJECTIVE: To evaluate the efficacy and safety of a fixed-dose, single-capsule budesonide-formoterol combination, in comparison with budesonide alone, in patients with uncontrolled asthma. METHODS: This was a randomized, double-blind, multicenter, phase III, parallel clinical trial, comparing the short-term efficacy and safety of the combination of budesonide (400 µg) and formoterol (12 µg), with those of budesonide alone (400 µg), both delivered via a dry powder inhaler, in 181 patients with uncontrolled asthma. The age of the patients ranged from 18 to 77 years. After a run-in period of 4 weeks, during which all of the patients received budesonide twice a day, they were randomized into one of the treatment groups. for 12 weeks. The treatment consisted of the administration of the medications twice a day for 12 weeks. The primary outcome measures were FEV1, FVC, and morning PEF. We performed an intention-to-treat analysis of the data. RESULTS: In comparison with the budesonide-only group patients, those treated with the budesonide-formoterol combination showed a significant improvement in FEV1 (0.12 L vs. 0.02 L; p = 0.0129) and morning PEF (30.2 L/min vs. 6.3 L/min; p = 0.0004). These effects were accompanied by good tolerability and safety, as demonstrated by the low frequency of adverse events, only minor adverse events having occurred. CONCLUSIONS: The single-capsule combination of budesonide and formoterol appears to be efficacious and safe. Our results indicate that this formulation is a valid therapeutic option for obtaining and maintaining asthma control. (ClinicalTrials.gov Identifier: NCT01676987 [http://www.clinicaltrials.gov/]).

Involvement of β3-adrenergic receptors in the control of food intake in rats

This study examined the food intake changes evoked by intracerebroventricular (icv) injection of a selective agonist (BRL37344, 2 and 20 nmol) or antagonist (SR59230A, 10 and 50 nmol) of β3-adrenergic receptors in 24-h fasted rats (adult male Wistar rats, 200-350 g, N = 6/treatment). The animals were also pretreated with saline icv (SAL) or SR59230A (50 nmol) followed by BRL37344 (20 nmol) or SAL in order to determine the selectivity of the effects evoked by BRL37344 on food intake or the selectivity of the effects evoked by SR59230A on risk assessment (RA) behavior. The highest dose of BRL37344 (N = 7) decreased food intake 1 h after the treatment (6.4 ± 0.5 g in SAL-treated vs 4.2 ± 0.8 g in drug-treated rats). While both doses of SR59230A failed to affect food intake (5.1 ± 1.1 g for 10 nmol and 6.0 ± 1.8 g for 50 nmol), this treatment reduced the RA frequency (number/30 min) (4 ± 2 for SAL-treated vs 1 ± 1 for 10 nmol and 0.5 ± 1 for 50 nmol SR59230A-treated rats), an ethological parameter related to anxiety. While pretreatment with SR59230A (7.0 ± 0.5 g) abolished the hypophagia induced by BRL37344 (3.6 ± 0.9 g), BRL37344 suppressed the reduction in RA frequency caused by SR59230A. These results show that the hypophagia caused by BRL37344 is selectively mediated by β3-adrenergic receptors within the central nervous system. Moreover, they suggest the involvement of these receptors in the control of anxiety.

Comparative effects of conventional B-blockers and nebivolol on psychomotor performances in healthy volunteers: a preliminary report.

The present study was under taken to assess the comparative effects of nebivolol with propranolol and atenolol on psychomotor performances. Thirty healthy volunteers were randomized into three groups with n=10 in each group. Each subject received single dose of one of the three medications (nebivolol 5 mg, atenolol 50 mg and propranolol 40 mg) in morning (9:00 AM). Just before administering the drug, the pre-drug scores were taken, followed by post drug score obtained for consecutive six hours. Psychomotor assessment was carried out by three tests Simple Reaction Timer (SRT), Critical Flicker Fusion Frequent Threshold (CFFT) and Digit Cancellation Test (DCT). The results of present study indicate that single doses of atenolol and propranolol produced significant impairment of psychomotor performance. Nebivolol also impaired psychomotor performance tests in the similar fashion to atenolol and propranolol. Hence, the findings of the present study correlate with the lipophilic nature of the nebivolol.

Eficácia do formoterol na reversão imediata do broncoespasmo / Efficacy of inhaled formoterol in reversing bronchoconstriction

OBJETIVO: Avaliar efetividade e rapidez de ação do formoterol liberado através de inalador para pó seco na reversão de broncoespasmo induzido pela metacolina. MÉTODOS: Avaliaram-se prospectivamente 84 pacientes com queda do volume expiratório forçado no primeiro segundo 20 por cento após inalação de metacolina. Todos estavam sob investigação de sintomas respiratórios de etiologia não definida. Foram randomizados 41 pacientes para receber 200 mcg de fenoterol spray e 43 para receber 12 mcg de formoterol sob a forma de inalador de pó seco para reversão imediata do broncoespasmo. Avaliaram-se a queda no volume expiratório forçado no primeiro segundo inicial, dose provocadora de queda de 20 por cento do volume expiratório forçado no primeiro segundo inicial, e volume expiratório forçado no primeiro segundo após cinco e dez minutos da administração dos fármacos. RESULTADOS: Não houve diferença significativa entre os grupos em relação ao sexo, idade, peso, altura, dose provocadora de queda de 20 por cento do volume expiratório forçado no primeiro segundo, volume expiratório forçado no primeiro segundo inicial e pós-metacolina. A melhora do volume expiratório forçado no primeiro segundo após uso do broncodilatador foi de 34 por cento (cinco minutos) e 50,1 por cento (dez minutos) no primeiro grupo, e 46,5 por cento (cinco minutos) e 53,2 por cento (dez minutos) no segundo. CONCLUSÃO: O efeito broncodilatador do formoterol após cinco e dez minutos da indução de broncoespasmo pela metacolina foi similar ao do fenoterol. O formoterol, além de ser um broncodilatador de longa duração, tem também rápido início de ação, sugerindo que possa ser empregado como medicação de resgate nas crises de broncoespasmo.

OBJECTIVE: To evaluate the effectiveness and onset of action of formoterol delivered by dry-powder inhaler in reversing methacholine-induced bronchoconstriction. METHODS: Patients presenting a drop in forced expiratory volume in one second > 20 percent after methacholine inhalation were included. A total of 84 patients were evaluated. All of the participating patients presented respiratory symptoms of unknown origin, which were being investigated. The patients were randomized to receive 200 æg of spray fenoterol (n = 41) or 12 æg of dry-powder inhaler formoterol (n = 43), both administered in order to achieve immediate reversal of methacholine-induced bronchoconstriction. We evaluated the decrease in forced expiratory volume in one second (in relation to the baseline value) after methacholine challenge and the dose of methacholine required to provoke a drop of 20 percent in forced expiratory volume in one second, as well as the increase in forced expiratory volume in one second (in relation to the baseline value) at five and ten minutes after bronchodilator use. RESULTS: There were no significant differences related to gender, age, weight, height or dose of methacholine required to provoke a drop of 20 percent in forced expiratory volume in one second. Nor were there any significant differences in terms of baseline or post-methacholine forced expiratory volume in one second. In the fenoterol group, the mean postbronchodilator increase in forced expiratory volume in one second increase was 34 percent (at five minutes) and 50.1 percent (at ten minutes), compared with 46.5 percent (at five minutes) and 53.2 percent (at ten minutes) in the formoterol group. CONCLUSION: The bronchodilator effect of formoterol at five and ten minutes after methacholine-induced bronchoconstriction was similar to that of fenoterol. Despite being a long-acting bronchodilator, formoterol also has a rapid onset of action, which suggests that it could be employed ...

Inhaled formoterol versus ipratropium bromide in chronic obstructive pulmonary disease.

BACKGROUND: Short-acting anticholinergic bronchodilator, ipratropium bromide has been recommended as first-line drug in chronic obstructive pulmonary disease (COPD). More recently, long acting beta2-agonist (LABA) bronchodilators such as formoterol have been shown to be useful in COPD. Limited information is available on the relative efficacy of these two drugs in COPD. METHODOLOGY: A randomised, double-blind, cross-over, placebo-controlled study was carried out. Forty-four stable patients with COPD received single doses of formoterol (12 microg), ipratropium bromide (40 microg) or placebo, administered through a metered-dose inhaler on three consecutive days in a random order. Spirometry, static lung volumes, pulse rate and blood pressure, and assessment of sensation of dyspnoea at rest using a visual analog scale (Borg Scale) were recorded at baseline. Subsequently, these were repeated for assessment of response: spirometry at 5, 30 and 60 minutes and static lung volumes, pulse rate, blood pressure and dyspnoea measurement at 60 minute. RESULTS: Formoterol resulted in greater immediate improvement in lung function, with the change in FEV1 at 5 min being greater than that observed with ipratropium. The changes in static lung volumes were similar between the two but superior to placebo. Both the drugs reduced dyspnoea. Formoterol produced a significantly greater increase in heart rate and systolic blood pressure as compared to ipratropium, although the magnitude of these changes was small and clinically unimportant. CONCLUSIONS: Single therapeutic doses of formoterol and ipratropium bromide are equally effective in improving lung function and reducing dyspnoea. However, formoterol appears to be a better bronchodilator producing a faster improvement in lung function.

Improving quality of life in asthmatic children.

OBJECTIVE: To assess quality of life changes in pediatric asthmatic patients switched into a single inhaler device of Budesonide/Formoterol. METHODS: Thirty pediatric patients (ages 6-15 years) with moderate to severe chronic asthma previously treated with inhaled beclometasone dipropionate at a daily dose of 400 g were selected to participate in an open label study. At the baseline- phase (one month), pulmonary function tests (PFTs), indicators of asthma control, and a quality of life assessment (using a special questionnaire) were evaluated. Patients were initiated on a single inhaler device containing budesonide 160 g/formoterol 4.5 microg, one inhalation twice daily instead of their previous inhaled corticosteroid and followed for two months. PFTs, indicators of asthma control, and a quality of life assessment were evaluated at each visit. RESULTS: After switching to the new therapy, patients showed significant changes towards better quality of life in all aspects. The overall score dropped from 1.75+/- 0.04 to 0.80 +/- 0.07 (mean +/- SEM), p< 0.001 (Score scale varies between 0: excellent to 2: very bad Health related quality of life). There was an improvement in the PFTs, where the FEV1% improved from 62.7+/- 2.8 to 87.4 +/- 4.6 (mean +/- SEM), and the FVC% improved from 83.2 +/- 3.5 to 101.9 +/- 5.3 (mean +/-SEM), p < 0.001, and better control of asthma. CONCLUSION: Switching treatment from beclomethasone dipropionate to budesonide/formoterol combination appeared to improve quality of life in the patient population evaluated and in the appropriate clinical indices.

Monitoring the therapeutic efficacy of antimalarials against uncomplicated falciparum malaria in Thailand.

Increasing antimalarial drug-resistance is an important problem in Thailand. The results of monitoring the antimalarial efficacy are used in decision-making about using antimalarials to treat uncomplicated falciparum malaria in Thailand. In 2002, 552 patients with uncomplicated malaria were treated according to the Thai National Drug Policy, with mefloquine 25 mg/kg plus artesunate 12 mg/kg and primaquine 30 mg in divided doses for 2 days in high-mefloquine-resistant areas; mefloquine 15 mg/kg plus primaquine 30 mg in non- or low-mefloquine-resistant areas; mefloquine 15 mg/kg plus artesunate 12 mg/kg and primaquine 30 mg in divided doses for 2 days or Coartem (6-dose regimen for adult contains 480 mg artemether and 2880 mg lumefantrine) plus primaquine 30 mg given over 3 days in moderate-mefloquine-resistant areas. The study shows that mefloquine, artesunate plus mefloquine, and artemether plus lumefantrine are effective in the treatment of uncomplicated malaria in most areas of Thailand except for Ranong and Kanchanaburi, where the first-line treatment regimen should be revised.

Comparative clinical trial of two-fixed combinations dihydroartemisinin-napthoquine-trimethoprim (DNP) and artemether-lumefantrine (Coartem/Riamet) in the treatment of acute uncomplicated falciparum malaria in Thailand.

An open randomized comparison of two-fixed dose artemisinin derivative-containing combination regimens was conducted in adults with acute uncomplicated multidrug resistant falciparum malaria in Thailand. DNP, a combination of dihydroartemisinin with napthoquine and trimethoprim developed recently in China, has been evaluated in China, Vietnam, Cambodia and Thailand. This study was performed to compare the safety, tolerability and efficacy of DNP and artemether-lumefantrine/Coartem. One hundred and thirty eligible uncomplicated falciparum malaria patients were enrolled into the study. Patients were randomly assigned in a 2:1 ratio into group A, which received DNP one tablet twice a day for one day; and group B, which received Coartem/Riamet four tablets twice a day for 3 days. The cure rates at 28-day were 99% and 97% in group A and group B, respectively. No serious adverse events occurred. We concluded that both DNP and Coartem/ Riamet were safe, well tolerated and highly efficacious in the treatment of acute uncomplicated falciparum malaria in Thailand.

Metabolic markers following beta-adrenoceptor agonist infusion in footshock-stressed rats

Stress hormones can alter metabolic functions in adipose tissue and liver, as well as the sensitivity of rat white adipocytes and rat atrial responses to ß-adrenergic agonists. In this study, we examined the effects of three daily footshock stress sessions on the plasma corticosterone, glucose, glycerol and triacylglycerol levels of fed, conscious male rats, and on the plasma glucose, glycerol and triacylglycerol levels of the same rats following iv infusions of ß-adrenergic agonists (isoproterenol: 0.4 nmol kg-1 min-1, noradrenaline: 5.0 æg kg-1 day-1, and BRL 37344 ([+ or -]-[4-(2-[(2-[3-chlorophenyl]-2-hydroxyethyl)amino]propyl)phenoxy]acetic acid), a selective ß3-adrenoceptor agonist: 0.4 nmol kg-1 min-1). Plasma corticosterone levels increased significantly after each stress session, while triacylglycerol levels increased after the first session and glucose increased after the second and third sessions. Glycerol levels were unaltered after stress. These results suggest that repeated footshock stress may induce a metabolic shift from triacylglycerol biosynthesis to glucose release by hepatic tissue, with glycerol serving as one of the substrates in both pathways. Stressed rats were more sensitive to infusion of noradrenaline plus prazosin and to infusion of isoproterenol, with elevated plasma glucose, glycerol and triacylglycerol levels. The higher sensitivity of stressed rats to isoproterenol and noradrenaline was probably related to the permissive effect of plasma corticosterone. Only BRL 37344 increased plasma glycerol levels in stressed rats, probably because ß3-adrenoceptors are not involved in hepatic triacylglycerol synthesis, thus allowing glycerol to accumulate in plasma

Formoterol en polvo seco, dos veces al día versus salbutamol aerosol, cuatro veces al día, en pacientes con asma estable / Inhaled formoterol (dry powder) twice daily versus salbutamol spray fourfold daily in patients with bronchial asthma

Material y método. Con un diseño abierto, aleatorio y multicéntrico, se compararon los efectos de formoterol en polvo seco inhalado con el sistema ISF, dos veces al día (12 mcg cada 12 h) contra salbutamol (200 mcg cuatro veces al día) en pacientes con asma bronquial. Se estudiaron 160 pacientes con este diagnóstico en cuatro centros especilaizados. La variable principal fue la medición del flujo espiratorio máximo (FEM) matutino y vespertino, evaluados antes de la medicación, así como la capacidad vital (CV), volumen espiratorio fozado en 1 segundo (VEF-1), otras variables para seguridad. Resultados. La administración de formoterol demostró ser superior en la evaluación del FEM matutino p<0.05, así como también en el VEF-1 matutino p<0.05 desde el primer mes. La frecuencia de experiencias adversas fue similar en ambos grupos. Además, se encontró un menor número de despertares nocturnos en el grupo con formoterol. Conclusiones. El formoterol es un agonista beta 2 seguro, eficaz y de larga acción que permite su adminsitración cada 12 h, que ofrece beneficios clínicos importantes sobre salbutamol

Bronchodilatation effects of dry powder formoterol fumarate in asthmatic patients.

Ten asthmatic patients were enrolled in our study of the effects of dry powder formoterol fumarate. The onset was 2-5 minutes and a long duration of action (over 12 hours) appeared. The mean baseline FEV1 was 1.67 liters (49-74%). Mean reversibility was 17 per cent (range 15-19%). There was no adverse effect in this study.

Maximum bronchodilator effect of pirbuterol and procaterol administered as sprays with and without an aerochamber

Objective of the study: To determine the maximal bronchodilator dose of procaterol and pirbuterol administered by inhalation with an without an aerochamber (Aerocâmera) to children with acute brinchial asthma attacks. Type of study: Prospective. 18 children (6-15 years of age) with acute bronchial asthma attacks (FEV1 < 80 per cents of the predicted value) received pirbuterol (N = 10) or procaterol (N = 8) by metered-dose inhaler, one puff every 5 minutes, for a total of five doses. During another acute attack, the same patient received the same medication with the aid of a spacer (Aerocâmera). Clinical evaluation and pulmonary function tests were performed 5 minutes after each inhaled dose. Results: For both drugs, maximal bronchodilation was obtained after the second dose. No significant side effects were observed even after procaterol doses of 50 µg or pirbuterol doses of 1000 µg. The results were unaffected by the use of the spacer. Conclusions: The doses that induced maximal bronchodilation were 400 µg pirbuterol and 20 µg procaterol Although the spacer did not change the results, it is a valuable aid for patients who have difficulty in using the metered-dose inhaler (M.D.I.)