在健康受试者群体药代动力学分析lanreotide Autogel:证据注射间隔2个月。

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Troconiz如果Cendros JM, Peraire C。拉米斯J,加里多MJ, Boscani PF, Obach R

在健康受试者群体药代动力学分析lanreotide Autogel:证据注射间隔2个月。

Pharmacokinet。2009年,48 (1):51 - 62。doi: 10.2165 / 0003088-200948010-00004。

PubMed ID

19071884 (在PubMed

]

文摘

背景和目的:Lanreotide是生长抑素类似物用于治疗肢端肥大症和神经内分泌肿瘤。本研究的目的是开发一种缓释制剂的药代动力学模型lanreotide Autogel深层皮下后政府在健康受试者,并探讨协变量的潜在影响,尤其是性和剂量。对象和方法:这是一个开放的,只有,随机、dose-ranging与这些相应平行的组织研究,随访4 - 7个月后在健康受试者药物管理局。包括健康白种人成熟女性受试者年龄在18 - 45年。受试者接受的快速静脉注射丸7 microg /公斤的速释lanreotide (lanreotide IRF)。在为期3天的洗脱期之后,参与者被随机分配接受一个深入皮下注射lanreotide Autogel剂量的60,90或120毫克。药代动力学和统计分析:血液样本为lanreotide决心获得第一次静脉注射丸后12小时后,在4 - 7月龄随访期间深入皮下管理lanreotide Autogel。数据在静脉注射和皮下安装同时使用NONMEM人口的方法((R))第六版软件。该模型验证使用数据从外部肢端肥大症患者。结果:总体而言,50名健康受试者(妇女和男性26日)24日收到一个lanreotide IRF的静脉注射剂量。 Of these, 38 subjects (18 women and 20 men) received a single subcutaneous dose of lanreotide Autogel 3 days after intravenous lanreotide IRF. The disposition of lanreotide was described by a three-compartment open model. The estimates of the total volume of distribution and serum clearance were 15.1 L and 23.1 L/h, respectively. The estimates of interindividual variability were <40%. To evaluate lanreotide Autogel pharmacokinetics, the absorption rate was modelled to decrease exponentially as a function of the natural logarithm of time. The absolute bioavailability after deep subcutaneous administration of lanreotide Autogel was 63%. The rate of absorption and bioavailability of lanreotide Autogel were independent of the administered dose in the range from 60 to 120 mg, and no significant effect of covariates (sex, dose, age or bodyweight) was found (p > 0.05). CONCLUSIONS: Population analysis allows a full description of the disposition of lanreotide after rapid intravenous bolus administration of lanreotide IRF (7 microg/kg) and the pharmacokinetics of lanreotide Autogel after a single deep subcutaneous injection (60, 90 or 120 mg) in healthy subjects. The model-based simulations provide support for the feasibility of extending the dosing interval for lanreotide Autogel to 56 days when given at 120 mg. The absorption profile of lanreotide Autogel was independent of the dose and was not affected by sex.

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药物

Lanreotide