RESUMO
A HPLC method was validated for quantification of (+)-calanolide A (1), a novel anti-HIV agent, in rat, dog and human plasma. The synthetic intermediate (+/-)-12-oxocalanolide A (2) was found to be a suitable internal standard. Compounds were extracted from plasma using a solid-phase C(18) cartridge and quantified over the assay range of 12.5 to 800 ng/ml. The method was utilized to determine (+)-calanolide A pharmacokinetics in rats, dogs and humans. This is the first report of a validated HPLC assay for determination of (+)-calanolide A concentrations in rat and dog plasma as well as human plasma obtained from clinical trials. There was no evidence of in vivo epimerization of (+)-calanolide A to its inactive epimer (+)-calanolide B (3).
Assuntos
Fármacos Anti-HIV/sangue , Cromatografia Líquida de Alta Pressão/métodos , Cumarínicos/sangue , Administração Oral , Animais , Fármacos Anti-HIV/administração & dosagem , Fármacos Anti-HIV/farmacocinética , Área Sob a Curva , Estudos de Coortes , Cumarínicos/administração & dosagem , Cumarínicos/farmacocinética , Cães , Feminino , Soronegatividade para HIV , Humanos , Masculino , Piranocumarinas , Ratos , Padrões de Referência , Reprodutibilidade dos Testes , Espectrometria de FluorescênciaRESUMO
Human intrusion into pristine habitats increases the likelihood of acquiring infectious agents from potentially infective ticks. As part of a larger human serological investigation into tick-borne illnesses, 3,000 ixodid ticks were collected during May, August, and November 1990 at Fort Chaffee, Arkansas. Ticks were examined to determine whether they harbor rickettsiae, ehrlichiae, and Borrelia burgdorferi, and to assess relationship to human exposure to tick-borne infections at Fort Chaffee, Ark. The overall tick infection rates with SFG rickettsiae, B. burgdorferi, and ehrlichiae were 4.8, 0.1, and 0.3%, respectively.