PubMed Health⌕ Search
Home/Archive/PubMed

PubMed · 14727963

Bosentan.

Amitabh Prakash·Caroline M Perry
View original source ↗Export metadata ↓

Abstract

Bosentan is a nonpeptide, specific, competitive, dual antagonist at both endothelin receptor subtypes (ET(A) and ET(B)). Orally administered bosentan effectively prevents endothelin 1-induced vasoconstriction in pulmonary vessels in patients with pulmonary arterial hypertension. Improvement in exercise capacity from baseline was significantly greater with bosentan than with placebo in two phase III trials in patients with WHO functional class III or IV pulmonary arterial hypertension (primary or associated with connective tissue disease) despite treatment with vasodilators, diuretics, anticoagulants, cardiac glycosides, or supplemental oxygen. The beneficial effects of bosentan on exercise capacity were maintained for at least 20 weeks. Compared with placebo, bosentan led to a significantly greater improvement from pretreatment values in secondary efficacy endpoints such as the Borg dyspnea index, WHO functional class, and cardiopulmonary hemodynamic parameters (cardiac index, pulmonary vascular resistance, pulmonary artery pressure, pulmonary capillary wedge pressure, mean right atrial pressure). Bosentan significantly reduced the incidence, and delayed the onset, of clinical worsening of pulmonary arterial hypertension compared with placebo. In published clinical trials, adverse events that occurred with similar or greater frequency with bosentan 125 mg twice daily than with placebo included headache, syncope, flushing and abnormal hepatic function. Those that occurred less frequently with bosentan 125 mg twice daily than with placebo included dizziness, worsening of symptoms of pulmonary arterial hypertension, cough and dyspnea.

Explore related subjects

Administration, OralAntihypertensive AgentsBosentanDose-Response Relationship, DrugDrug Administration ScheduleDrug InteractionsHumansHypertension, PulmonaryRandomized Controlled Trials as TopicSulfonamidesComparative StudyJournal ArticleReview

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Amitabh Prakash, Caroline M Perry. 2002. Bosentan.. https://doi.org/10.2165/00129784-200202050-00006

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

PubMed2007

Successful treatment with voriconazole of Aspergillus brain abscess in a boy with medulloblastoma.

Invasive aspergillosis is an increasing problem in immuno-incompetent patients after prolonged steroid therapy, cancer radio-chemotherapy, and bone marrow or solid organ transplantation. Cerebral aspergillosis is a well-described complication of the invasive aspergillosis but only in rare cases, the brain is the sole site of infection. Despite increasing availability of antifungal drugs, the prognosis of cerebral aspergillosis is poor. We report on an 11-year-old boy with medulloblastoma in the area of the fourth ventricle. Following tumor surgery and radio-chemotherapy, several abscess-like structures occurred in the operating field. After incomplete abscess, resection histology and culture confirmed a localized Aspergillus fumigatus infection. The initial treatment of the Aspergillus fumigatus infection with conventional amphotericin B failed, and treatment with the triazole voriconazole was started. Intravenous treatment with voriconazole resulted in a reduction of the Aspergillus fumigatus abscess. After switching to oral ambulatory therapy, the Aspergillus fumigatus abscess increased in size. To improve treatment, voriconazole dosage was adapted to reach drug concentrations in cerebrospinal fluid (CSF) above the minimal fungicidal concentration and plasma specimens. During the concentration-controlled voriconazole therapy for a period of 18 months, a complete response was achieved.

Administration, Oral↗
PubMed2007

Temozolomide and intravenous irinotecan for treatment of advanced Ewing sarcoma.

BACKGROUND: Preclinical models show sequence-dependent synergy with the combination of temozolomide and irinotecan, and a Phase I trial has demonstrated the combination to be tolerable and active in children with relapsed solid tumors. Because responses were seen in patients with Ewing sarcoma (ES) on that trial, additional patients were treated with this combination following study completion. PROCEDURE: We reviewed data from all ES patients treated with temozolomide and irinotecan at four institutions, including seven patients treated on the above Phase I trial. RESULTS: Sixteen patients received a total of 95 courses, with a median of five courses per patient. All patients had either progressive disease (PD) during initial therapy (n = 5) or relapse within 2 years of diagnosis (n = 11). Twelve patients had metastatic disease at diagnosis, including 5 with bone and/or marrow metastases. Patients received oral temozolomide 100 mg/m(2)/day on days 1-5 plus intravenous irinotecan 10-20 mg/m(2)/day on days 1-5 and 8-12, with courses repeated every 21-28 days. We observed 1 complete, 3 partial, and 3 minor responses in 14 evaluable patients, with a median duration of response of 30 weeks. Planned 21-day courses were tolerable and no more toxic than 28-day courses. Myelosuppression was minimal despite heavy pretreatment. Grade 3-4 diarrhea occurred in 11% of courses and was related to higher irinotecan doses. Over 600 irinotecan doses were administered uneventfully at home. CONCLUSIONS: Temozolomide and protracted intravenous irinotecan given in 21-day courses was tolerable and active in patients with advanced ES. Home administration of irinotecan with temozolomide was safe and is reasonable palliative therapy. A formal Phase II study using a uniform dose and schedule is warranted to better define activity.

Administration, Oral↗
PubMed2007

Medical and non-medical barriers to outpatient treatment of fever and neutropenia in children with cancer.

BACKGROUND: A number of clinical trials have employed clinical criteria that can identify pediatric patients at low-risk for complicated episodes of fever and neutropenia (F&N) and have successfully treated low-risk patients in the outpatient setting. Despite this, inpatient management remains the standard of care. This trial tested the hypothesis that a strategy of initial hospitalization followed by continuation of therapy in the outpatient setting could be practically implemented in the majority of episodes. PROCEDURE: Patients presenting with F&N were initially evaluated to determine if they had high-risk clinical criteria that would exclude them from this approach. Eligible patients were then hospitalized and treated with iv antibiotics. On subsequent days the attending physician determined whether the patient had exhibited improvement and could continue therapy in the outpatient setting with oral antibiotics. Outpatients were seen three times weekly and continued antibiotics until recovery from F&N. RESULTS: Outpatient oral antibiotic therapy was practically implemented in less than one-quarter of episodes of pediatric F&N. Forty-nine percent of episodes were excluded from study by medical and social protocol exclusion criteria. One hundred five episodes were enrolled and among these 59 episodes included outpatient management. Common barriers to outpatient care included serious medical comorbidities, non-medical barriers including language and distance of residence from the medical center, and lack of interest. The average duration of outpatient care was 3.6 days following an average of 3.5 days of hospitalization. Ninety percent did not require rehospitalization. They experienced no complications. CONCLUSIONS: In only a minority of episodes can outpatient antibiotic management be implemented. Medical comorbidities and social barriers can make the transition to outpatient care difficult. However, initial hospitalization followed by oral antibiotic outpatient management appears safe and effective for low-risk patients who exhibit good responses to initial antibiotic therapy in hospital.

Administration, Oral↗