Kramer W G, Feldman S, Broughton A, Strong J E, Hall S W, Holoye P Y
J Clin Pharmacol. 1978 Jul;18(7):346-52. doi: 10.1002/j.1552-4604.1978.tb01604.x.
A series of studies were carried out to investigate the pharmacokinetics of the antineoplastic antibiotic bleomycin in patients with neoplastic disorders. Drug was administered by long (four to five days) and short (10 minutes) zero-order infusions, and serial plasma and urine samples were collected. Serum and urine bleomycin concentrations were determined by radioimmunoassay. The disposition of bleomycin after the 10-minute infusion was described by a two-compartment open model. However, following multiple-day infusion estimates were obtained that were inconsistent with those from the short infusion. Parameters from the long infusions agreed with those from the short infusion when terminal plasma bleomycin levels less than 10 microunits/ml were excluded. The time to reach steady state following the long infusion (ca. 12 hours) was consistent with the half-life (3 hours) predicted by the short infusion and the long infusion excluding levels less than 10 microunits/ml. Possible explanations include assay interference by an unknown metabolite or strong binding of drug to tissues with release at a rate much less than the apparent rate of elimination of drug from the body.
开展了一系列研究以调查抗肿瘤抗生素博来霉素在肿瘤疾病患者体内的药代动力学。通过长时间（四至五天）和短时间（10分钟）零级输注给药，并采集系列血浆和尿液样本。通过放射免疫分析法测定血清和尿液中的博来霉素浓度。10分钟输注后博来霉素的处置情况由二室开放模型描述。然而，多日输注后的估计值与短时间输注的估计值不一致。当排除终末血浆博来霉素水平低于10微单位/毫升的情况时，长时间输注的参数与短时间输注的参数一致。长时间输注后达到稳态的时间（约12小时）与短时间输注以及排除低于10微单位/毫升水平后的长时间输注所预测的半衰期（3小时）一致。可能的解释包括未知代谢物的检测干扰或药物与组织的强烈结合，其释放速率远低于药物从体内消除的表观速率。
