Zimmerman C L, O'Connell M B, Soria I
College of Pharmacy, University of Minnesota, Minneapolis 55455.
Pharm Res. 1990 Jan;7(1):96-102. doi: 10.1023/a:1015852012968.
To determine whether urinary alkalinization had an effect on the plasma pharmacokinetics and pharmacodynamics of phenylpropanolamine, a double-blind crossover study was conducted in four healthy, normotensive male volunteers. The subjects received 25 mg immediate-release phenylpropanolamine and either placebo or sodium bicarbonate in a balanced randomized order. The bicarbonate treatment consisted of 6 g sodium bicarbonate 30 min prior to the phenylpropanolamine and then 3 g sodium bicarbonate every 4 hr for the next 16 hr. During the control treatment, phenylpropanolamine and a placebo for bicarbonate (lactose) were given on the same schedule. Blood and urine samples were collected over 24 hr and analyzed by HPLC. A supine blood pressure and pulse were obtained before each blood sample. The bicarbonate treatment significantly increased the urine pH throughout the study period and decreased phenylpropanolamine renal clearance by 33.5%. The apparent total-body clearance was also decreased by 31.5% and resulted in higher postabsorptive plasma phenylpropanolamine concentrations in each subject as compared to the control treatment. Both systolic and diastolic blood pressures changed significantly from baseline in both treatments. The bicarbonate treatment was accompanied by significantly higher diastolic blood pressures than in the control treatment, but there was no effect on systolic blood pressures. Generally, when the blood pressure-concentration pairs were plotted chronologically, clockwise hysteresis curves resulted. Heart rates did not change significantly from baseline values for either treatment. In this small group of normotensive healthy male volunteers, urinary alkalinization significantly depressed the renal clearance of phenylpropanolamine, producing higher postabsorptive phenylpropanolamine plasma concentrations and a small but significant increase in the diastolic blood pressure.
为确定尿液碱化是否对苯丙醇胺的血浆药代动力学和药效学有影响，对4名健康、血压正常的男性志愿者进行了一项双盲交叉研究。受试者以平衡随机顺序接受25mg速释苯丙醇胺以及安慰剂或碳酸氢钠。碳酸氢钠治疗方案为在服用苯丙醇胺前30分钟给予6g碳酸氢钠，随后在接下来的16小时内每4小时给予3g碳酸氢钠。在对照治疗期间，按照相同的时间表给予苯丙醇胺和碳酸氢盐的安慰剂（乳糖）。在24小时内采集血液和尿液样本，并通过高效液相色谱法进行分析。在采集每个血样前测量仰卧位血压和脉搏。在整个研究期间，碳酸氢钠治疗显著提高了尿液pH值，并使苯丙醇胺的肾脏清除率降低了33.5%。表观全身清除率也降低了31.5%，与对照治疗相比，每个受试者吸收后血浆苯丙醇胺浓度更高。两种治疗中收缩压和舒张压均较基线有显著变化。碳酸氢钠治疗组的舒张压显著高于对照治疗组，但对收缩压没有影响。一般来说，当按时间顺序绘制血压-浓度对时，会得到顺时针滞后曲线。两种治疗的心率与基线值相比均无显著变化。在这一小群血压正常的健康男性志愿者中，尿液碱化显著降低了苯丙醇胺的肾脏清除率，使吸收后苯丙醇胺血浆浓度升高，并使舒张压有小幅但显著的升高。
