RESUMO
The human inflammatory response can result in the alteration of drug clearance through effects on metabolizing enzymes or transporters. In this article we briefly review the theory of how cancer can lead to indirect changes in drug metabolism, review acute phase proteins and cytokines as markers of changes in cytochrome P450 (CYP) activity in cancer patients, and provide clinical case examples of how the inflammation in advanced cancer patients can lead to altered CYP-mediated drug clearance.
Assuntos
Neoplasias/metabolismo , Proteínas de Fase Aguda/metabolismo , Sistema Enzimático do Citocromo P-450/metabolismo , Citocinas/metabolismo , Interações Medicamentosas , Humanos , Imidazóis/farmacologia , Indóis/farmacocinética , Inflamação/metabolismo , Metanálise como Assunto , Midazolam/farmacocinética , Neoplasias/imunologia , Proteína Quinase C beta/antagonistas & inibidores , Piridinas/farmacologia , Proteínas Quinases p38 Ativadas por Mitógeno/antagonistas & inibidores , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismoRESUMO
The objective of this study was to measure the steady-state cerebrospinal fluid (CSF) concentration of LY450108 and LY451395 (positive modulators of AMPA receptors) in healthy subjects after the administration of 1 mg and 5 mg. Secondary objectives included the evaluation of safety, pharmacokinetics, and steady-state ratio of plasma:CSF concentrations of LY450108 and LY451395 after multiple dosing. This study was an open-label, multiple oral dose study evaluating 1 mg and 5 mg LY450108 and 1 mg and 5 mg LY451395 in 12 (3 subjects per dosing group) healthy subjects, aged 18 to 49 years. Twelve healthy male subjects completed the study. LY450108 and LY451395 were quantifiable in CSF after 1-mg and 5-mg multiple-dose administrations with plasma:CSF ratio of 82:1 and 44:1, respectively. LY450108 and LY451395 1 mg and 5 mg were measured in the CSF. Single and multiple oral doses of LY450108 and LY451395 were determined to be safe and well tolerated in healthy subjects.
Assuntos
Compostos de Bifenilo/efeitos adversos , Compostos de Bifenilo/farmacocinética , Receptores de AMPA/agonistas , Sulfonamidas/efeitos adversos , Sulfonamidas/farmacocinética , Adulto , Área Sob a Curva , Compostos de Bifenilo/líquido cefalorraquidiano , Relação Dose-Resposta a Droga , Meia-Vida , Humanos , Masculino , Taxa de Depuração Metabólica , Sulfonamidas/líquido cefalorraquidianoRESUMO
Studies were designed to evaluate the amaranth method for measuring chlorine dioxide in water. Specifically, the effects of pH and temperature are examined for the amaranth method. The results of interference studies are reported for free available chlorine species, chlorite ion, chlorate ion, iron (III) ion, oxidized manganese, and monochloramine. Additional research focused on selectivity enhancement for chlorine dioxide over free available chlorine using ammonia/ammonium chloride buffer and gas diffusion-flow injection analysis. The results of method detection limit and accuracy and precision studies are reported for measuring chlorine dioxide in the presence of free available chlorine.
