RESUMO
Vascular and angiogenic processes provide an important target for novel cancer therapeutics. Dynamic contrast-enhanced magnetic resonance imaging is being used increasingly to noninvasively monitor the action of these therapeutics in early-stage clinical trials. This publication reports the outcome of a workshop that considered the methodology and design of magnetic resonance studies, recommending how this new tool might best be used.
Assuntos
Inibidores da Angiogênese/uso terapêutico , Antineoplásicos/uso terapêutico , Imageamento por Ressonância Magnética , Neoplasias/irrigação sanguínea , Neoplasias/tratamento farmacológico , Ensaios Clínicos como Assunto , Estudos de Avaliação como Assunto , Reprodutibilidade dos Testes , Terminologia como AssuntoAssuntos
Inibidores da Angiogênese/uso terapêutico , Ensaios Clínicos como Assunto/métodos , Angiografia por Ressonância Magnética/métodos , Neoplasias/irrigação sanguínea , Neovascularização Patológica/tratamento farmacológico , Desenho de Fármacos , Humanos , Neoplasias/tratamento farmacológico , Reprodutibilidade dos TestesRESUMO
Healthy human volunteers orally ingested escalating doses of up to 6 g nicotinamide in capsule form on an empty stomach. Some side-effects were seen although these were mild and transient. HPLC analysis of blood samples showed peak plasma levels, typically within 45 min after ingestion, which were linearly dependent on dose ingested. The elimination half-life and AUC were also found to increase with drug dose, although these increases were non-linear. Pharmacokinetic studies were also performed in female CDF1 mice with C3H mammary carcinomas grown in the right rear foot. Analysis of blood and tumour samples taken from mice injected i.p. with nicotinamide doses between 100-1000 mg/kg showed similar characteristics as the human data, although the elimination half-lives were not dose-dependent. The average peak plasma concentration of 160 micrograms/ml measured in humans after taking 6 g of nicotinamide was equivalent to that seen in mice after injecting 171 mg/kg. Using a regrowth delay assay the enhancement of radiation damage by nicotinamide in this mouse tumour was found to be independent of drug dose from 100-1000 mg/kg, resulting in a constant 1.3-fold increase in radiation response. Doses of nicotinamide that can be tolerated clinically should therefore produce adequate enhancements of radiation damage in human tumours.