Bioavailability of oral trimetrexate in patients with acquired immunodeficiency syndrome.
AUTOR(ES)
Rogers, P
RESUMO
The combination of the lipophilic antifolate trimetrexate and the rescue agent leucovorin has shown promise in the treatment of Pneumocystis carinii pneumonia in patients with acquired immunodeficiency syndrome. The pharmacokinetic behavior of trimetrexate administered either by intravenous bolus or orally was studied in six patients with acquired immunodeficiency syndrome with a reversed-phase high-pressure liquid chromatography assay. The mean clearance following bolus injection was 38 ml/min per m2, with a range of 15 to 55 ml/min per m2. The postdistributive half-life ranged from 6 to 16 h. With oral administration, the mean bioavailability was 44% (range, 19 to 67%). An oral dose of 60 mg/m2 (162 mumol/m2) resulted in concentrations in plasma that approximated those achieved with a 30-mg/m2 (81-mumol/m2) intravenous dose. The toxicity of this combination regimen was minimal. It appears that the oral route is a practical route of administration for trimetrexate in patients with acquired immunodeficiency syndrome requiring long-term outpatient treatment or prophylaxis for P. carinii pneumonia.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=172168Documentos Relacionados
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