Hageman R J, de Zeeuw R A, Greving J E, Krann J J, Koëter G H
Department of Toxicology, State University, Groningen, The Netherlands.
Biopharm Drug Dispos. 1988 May-Jun;9(3):301-14. doi: 10.1002/bod.2510090308.
Three healthy volunteers received single doses of reproterol (D 1959) by means of intravenous infusion, oral and aerosol application, respectively. Administrations were separated by at least 1 week. Plasma levels were measured by means of high performance liquid chromatography. After infusion, plasma levels showed a steep decline, indicative for a rapid distribution. Even though relatively large amounts of drug were given (up to 540 micrograms), this phenomenon caused reproterol levels to drop to values near or below the limit of reliable quantitation (1 ng ml-1) within 60 to 90 min. After oral administration of one or two tablets (containing 20 mg reproterol HCl per tablet), a very short lag time could be observed, indicating fast absorption. After one tablet, plasma level maxima (of plateau-type) were 5-6 ng ml-1 and 2-3 ng ml-1 in two subjects, respectively. After two tablets, plateau level maxima around 18 ng ml-1 and 9 ng ml-1 were found, respectively. After inhalation of a metered aerosol (two puffs of 500 micrograms each) the drug appeared in plasma within minutes, albeit at very low levels, and usually remained detectable at the sub-nanogram level during the time of the experiment (2 h). Due to the very low levels and to some oscillations in the plasma concentration-time curves, a detailed pharmacokinetic assessment could not be carried out. Effects on heart rate and blood pressure were negligible. Only during the infusion of high doses (540 micrograms) was there an increase in heart rate of about 50 to 120 beats min-1. Other side-effects were also negligible.
三名健康志愿者分别通过静脉输注、口服和气雾剂吸入的方式接受了单次剂量的瑞普特罗（D 1959）。给药间隔至少为1周。血浆水平通过高效液相色谱法测定。输注后，血浆水平呈急剧下降，表明分布迅速。尽管给予了相对大量的药物（高达540微克），但这种现象导致瑞普特罗水平在60至90分钟内降至接近或低于可靠定量限（1纳克/毫升）的值。口服一或两片（每片含20毫克盐酸瑞普特罗）后，可观察到非常短的滞后时间，表明吸收迅速。服用一片后，两名受试者的血浆水平最大值（平台型）分别为5 - 6纳克/毫升和2 - 3纳克/毫升。服用两片后，分别发现平台水平最大值约为18纳克/毫升和9纳克/毫升。吸入定量气雾剂（每次两喷，每喷500微克）后，药物在数分钟内出现在血浆中，尽管水平非常低，并且在实验期间（2小时）通常在亚纳克水平仍可检测到。由于水平非常低以及血浆浓度 - 时间曲线存在一些波动，无法进行详细的药代动力学评估。对心率和血压的影响可忽略不计。仅在输注高剂量（540微克）期间，心率增加约50至120次/分钟。其他副作用也可忽略不计。
