Swart P J, de Zeeuw R A
Department of Analytical Chemistry and Toxicology, University Centre for Pharmacy, Groningen, The Netherlands.
J Pharm Sci. 1993 Feb;82(2):200-3. doi: 10.1002/jps.2600820217.
The pharmacokinetics of the dopamine D2 agonist S(-)-2-(N-propyl-N-2-thienylethylamino)-5-hydroxytetralin (1, N-0923) after intravenous, intraperitoneal, and oral administration was studied in freely moving male and female albino Wistar rats. In all cases, the dose was 10 mumol.kg-1. Levels of 1 in plasma were monitored up to 6 h after dosing by high-performance liquid chromatography. A biphasic disappearance pattern with a rapid distribution phase was observed in the curve of concentration in plasma versus time. Pharmacokinetic analysis based on a two-compartment model with elimination from the central compartment yielded the following parameters for male rats (mean +/- standard deviation, n = 3): elimination half-life was 108 +/- 7 min, apparent volume of distribution of the central compartment was 397 +/- 44 mL.kg-1, the plasma clearance was 32 +/- 4 mL.min-1.kg-1, and the apparent volume of distribution at steady state was 2.29 +/- 0.25 L.kg-1. No significant difference (analysis of variance p value > 0.25) was found in the pharmacokinetic data between male and female rats. An extremely fast absorption was found after intraperitoneal administration. Maximal concentrations in plasma were often observed at the first time point 5 min after dosing. The bioavailability (mean +/- standard deviation, n = 3) was 7.9 +/- 2.7% for male rats and 6.5 +/- 2.1% for female rats. An increase of the elimination half-life of at least 40% for male rats and 300% for female rats was observed, indicating dose-dependent kinetics after intraperitoneal administration.(ABSTRACT TRUNCATED AT 250 WORDS)
在自由活动的雄性和雌性白化Wistar大鼠中，研究了多巴胺D2激动剂S(-)-2-(N-丙基-N-2-噻吩基乙氨基)-5-羟基四氢萘(1，N-0923)静脉注射、腹腔注射和口服给药后的药代动力学。在所有情况下，剂量均为10 μmol·kg-1。通过高效液相色谱法监测给药后6小时内血浆中1的水平。血浆浓度与时间曲线呈现出具有快速分布相的双相消失模式。基于从中央室消除的二室模型进行药代动力学分析，得出雄性大鼠的以下参数(平均值±标准差，n = 3)：消除半衰期为108±7分钟，中央室的表观分布容积为397±44 mL·kg-1，血浆清除率为32±4 mL·min-1·kg-1，稳态时的表观分布容积为2.29±0.25 L·kg-1。雄性和雌性大鼠的药代动力学数据之间未发现显著差异(方差分析p值> 0.25)。腹腔注射后发现吸收极快。给药后5分钟的第一个时间点经常观察到血浆中的最大浓度。雄性大鼠的生物利用度(平均值±标准差，n = 3)为7.9±2.7%，雌性大鼠为6.5±2.1%。观察到雄性大鼠的消除半衰期至少增加40%，雌性大鼠增加300%，表明腹腔注射后存在剂量依赖性动力学。(摘要截断于250字)
