Jaehde U, Sörgel F, Reiter A, Sigl G, Naber K G, Schunack W
IBMP-Institute for Biomedical and Pharmaceutical Research, Nürnberg-Heroldsberg, Germany.
Clin Pharmacol Ther. 1995 Nov;58(5):532-41. doi: 10.1016/0009-9236(95)90173-6.
Probenecid-sensitive anion transport systems may be involved in distribution and elimination processes of anionic drugs. The aim of this study was to determine the effect of multiple probenecid treatment on the pharmacokinetic disposition of the zwitterionic fluoroquinolone ciprofloxacin in 12 healthy volunteers.
A single intravenous dose of 200 mg ciprofloxacin was given with and without multiple oral administration of probenecid in a randomized crossover fashion. Serial plasma, urine, saliva, tear, and sweat samples were drawn and analyzed for ciprofloxacin and its 2-aminoethylamino-metabolite (M1) by reversed-phase HPLC.
Plasma area under the concentration-time curve and elimination half-life of ciprofloxacin were increased (p < 0.05), and urinary recovery and total and renal clearance decreased (p < 0.05) in the presence of probenecid. Nonrenal clearance and volume of distribution did not differ significantly with and without coadministration of probenecid. Peak plasma concentration, plasma area under the concentration-time curve, and elimination half-life of M1 were increased (p < 0.05) because of the higher amount of M1 formed and the reduced renal clearance (p < 0.05) of the metabolite. Saliva, tear, and sweat exposure were elevated (p < 0.05), but the alterations can be attributed primarily to the different kinetics of ciprofloxacin in plasma.
Coadministration of probenecid altered the renal excretion and hence the plasma concentrations of ciprofloxacin. Metabolite kinetics and distribution into saliva, tears, and sweat were affected accordingly, but there was no direct effect of probenecid on these processes. This type of drug-drug interaction might be of clinical relevance when ciprofloxacin is combined with drugs eliminated by the organic anion transport system in the kidney tubules.
丙磺舒敏感的阴离子转运系统可能参与阴离子药物的分布和消除过程。本研究的目的是确定多次给予丙磺舒对12名健康志愿者中两性离子氟喹诺酮环丙沙星药代动力学处置的影响。
采用随机交叉方式，在给予和不给予多次口服丙磺舒的情况下，静脉注射单剂量200mg环丙沙星。采集系列血浆、尿液、唾液、泪液和汗液样本，通过反相高效液相色谱法分析环丙沙星及其2-氨基乙胺代谢物（M1）。
在存在丙磺舒的情况下，环丙沙星的血浆浓度-时间曲线下面积和消除半衰期增加（p<0.05），尿回收率以及总清除率和肾清除率降低（p<0.05）。丙磺舒合用时与不合用时，非肾清除率和分布容积无显著差异。由于形成的M1量增加以及该代谢物的肾清除率降低（p<0.05），M1的血浆峰浓度、血浆浓度-时间曲线下面积和消除半衰期增加（p<0.05）。唾液、泪液和汗液中的暴露量升高（p<0.05），但这些变化主要可归因于环丙沙星在血浆中的不同动力学。
丙磺舒合用改变了环丙沙星的肾排泄，从而改变了其血浆浓度。代谢物动力学以及在唾液、泪液和汗液中的分布也相应受到影响，但丙磺舒对这些过程没有直接影响。当环丙沙星与通过肾小管有机阴离子转运系统消除的药物合用时，这种类型的药物相互作用可能具有临床相关性。
