Emanuelsson B M, Beermann B, Paalzow L K
Eur J Clin Pharmacol. 1987;32(4):395-401. doi: 10.1007/BF00543976.
Six healthy volunteers were given probenecid 0.5, 1 and 2 g p.o. and 0.5 g i.v. The protein binding of probenecid at different concentrations in human plasma was estimated by equilibrium dialysis. The free fraction was found to increase nonlinearly with increasing total probenecid concentration, up to a maximum free fraction of 26%. The plasma concentration-time data after the oral doses were described by a one-compartment open model with first-order absorption and Michaelis-Menten elimination. The mean absorption rate constant 0.0072 min-1 was dose-independent, and the maximal rate of elimination (mean 1429 micrograms/min) did not differ between doses whether calculated from the total or free concentrations. The Michaelis-Menten constant constant decreased significantly from 67.1 to 55.5 micrograms/ml as the dose increased from 1 g to 2 g, while the unbound Michaelis-Menten constant remained unchanged. The elimination of probenecid after the 0.5 g dose was in the linear region of the Michaelis-Menten elimination when calculated from the total and the free concentrations. The volume of distribution increased only slightly from 9.5 to 11.41 as the dose increased from 0.5 to 2 g, but the unbound volume of distribution decreased significantly from 164 to 99 1. Absorption was complete and was independent of the dose administered.
六名健康志愿者口服丙磺舒0.5克、1克和2克以及静脉注射0.5克。通过平衡透析法估算了丙磺舒在人血浆中不同浓度下的蛋白结合率。发现游离分数随丙磺舒总浓度的增加呈非线性增加，最高游离分数达26%。口服剂量后的血浆浓度-时间数据用具有一级吸收和米氏消除的一室开放模型进行描述。平均吸收速率常数0.0072分钟-1与剂量无关，无论从总浓度还是游离浓度计算，最大消除速率（平均1429微克/分钟）在不同剂量之间无差异。随着剂量从1克增加到2克，米氏常数从67.1微克/毫升显著降至55.5微克/毫升，而未结合的米氏常数保持不变。从总浓度和游离浓度计算，0.5克剂量后丙磺舒的消除处于米氏消除的线性区域。随着剂量从0.5克增加到2克，分布容积仅略有增加，从9.5升增至11.41升，但未结合分布容积从164升显著降至99升。吸收完全且与给药剂量无关。
