MORPHINE PHARMACOKINETICS AND EFFECTS ON SALIVATION AND CONTINUOUS REACTION-TIMES IN HEALTHY-VOLUNTEERS
MORPHINE PHARMACOKINETICS AND EFFECTS ON SALIVATION AND CONTINUOUS REACTION-TIMES IN HEALTHY-VOLUNTEERS
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DOI：
10.1097/00007691-199310000-00003
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发表时间：
1993-10-01
影响因子：
2.5
通讯作者：
HOGLUND, P
中科院分区：
文献类型：
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作者：
WESTERLING, D;FRIGREN, L;HOGLUND, P
10名健康志愿者在三个不同的场合以完全交叉设计静脉输注10 mg盐酸吗啡、20 mg盐酸吗啡口服溶液或30 mg硫酸吗啡新控释片剂。连续收集静脉血样14-24 h，并使用高效液相色谱法（HPLC）分析吗啡。重复测量所有受试者的连续反应时间（CRT）和流涎。整个手术过程中血氧饱和度保持正常。5例受试者至少发生1次恶心。使用二室模型计算的药代动力学参数与先前静脉注射和口服吗啡溶液的结果一致。吗啡口服溶液的绝对生物利用度为21.6%（15.4-27.7%; 95% CI），控释片的绝对生物利用度为17.1%（12.621; 95% CI）。6%; CI）。血浆浓度曲线中的第二峰强烈表明吗啡的肠肝循环（EHC）。进行替代药代动力学计算（包括EHC），并用于药代动力学-药效学模型，其中研究的效应与吗啡浓度良好相关。
Ten healthy volunteers were given an i.v. infusion of 10 mg morphine HCl, an oral solution of 20 mg morphine HCl, or a new controlled release tablet of 30 mg morphine sulphate on three separate occasions in a complete crossover design. Venous blood samples were collected serially for 14-24 h and analyzed for morphine using high-performance liquid chromatography (HPLC). Continuous reaction times (CRTs) and salivation were measured repeatedly in all subjects. Oxygen saturation remained normal throughout the procedure. Five subjects experienced nausea on at least one occasion. Pharmacokinetic parameters, calculated using a two-compartment model, were in accordance with previous results for i.v. and oral administration of morphine solutions. The absolute bioavailability of morphine in the oral solution was 21.6% (15.4-27.7%; 95% CI) and in the controlled release tablet, 17.1% (12.621. 6%; CI). Secondary peaks in the plasma concentration curves strongly indicated an enterohepatic circulation (EHC) of morphine. Alternative pharmacokinetic calculations, including EHC, were performed and used in a pharmacokinetic-pharmacodynamic model, in which the studied effects were well correlated to the concentrations of morphine.