Wang Jiping, Nation Roger L, Evans Allan M, Cox Susan
Centre for Pharmaceutical Research, School of Pharmacy and Medical Sciences, University of South Australia, North Terrace, Adelaide, SA 5000, Australia.
Pharm Res. 2004 Jun;21(6):982-8. doi: 10.1023/b:pham.0000029287.56914.42.
To investigate the effects of potential inhibitors of membrane transport on the tubular secretion of AM188, an antiviral guanosine analog, in the isolated perfused rat kidney (IPK).
AM188 was administered to the IPK perfusate as a bolus/infusion regimen. In inhibitor groups, probenecid, p-aminohippuric acid (PAH), cimetidine, or nitrobenzylthioinosine was added to the perfusing medium.
In control IPKs, the ratio of renal clearance of AM188 (CLR) to GFR was 7.7 +/- 0.51 (mean +/- SD). The CL(R)/GFR ratio for AM188 was 6.20 +/- 0.41*, 2.85 +/- 0.20*, 1.45 +/- 0.07*, and 0.80 +/- 0.01* when the concentration of probenecid in perfusate was 10, 50, 100, and 1000 microM, respectively (p < 0.05 compared to control group); the ratio was 7.71 +/- 0.38, 6.02 +/- 0.42, 1.71 +/- 0.15*, and 0.91 +/- 0.07* for the PAH group and 6.42 +/- 1.70*, 5.33 +/- 1.53*, 3.16 +/- 0.81*, and 1.21 +/- 0.20* for the cimetidine group when the concentrations were 10, 100, 1000 and 10,000 microM, respectively; and the ratio was 5.33 +/- 0.21* when the concentration of nitrobenzylthioinosine was 5 microM.
These results suggest that renal tubular secretion of AM188 involves organic anion and cation transport systems.
研究膜转运潜在抑制剂对离体灌注大鼠肾脏（IPK）中抗病毒鸟苷类似物AM188肾小管分泌的影响。
将AM188以推注/输注方案给予IPK灌注液。在抑制剂组中，将丙磺舒、对氨基马尿酸（PAH）、西咪替丁或硝基苄硫肌苷添加到灌注介质中。
在对照IPK中，AM188的肾清除率（CLR）与肾小球滤过率（GFR）之比为7.7±0.51（平均值±标准差）。当灌注液中丙磺舒浓度分别为10、50、100和1000微摩尔时，AM188的CL(R)/GFR比值分别为6.20±0.41*、2.85±0.20*、1.45±0.07和0.80±0.01（与对照组相比，p<0.05）；PAH组在浓度分别为10、100、1000和10000微摩尔时，该比值分别为7.71±0.38、6.02±0.42、1.71±0.15和0.91±0.07；西咪替丁组在浓度分别为10、100、1000和10000微摩尔时，该比值分别为6.42±1.70*、5.33±1.53*、3.16±0.81和1.21±0.20；当硝基苄硫肌苷浓度为5微摩尔时，该比值为5.33±0.21*。
这些结果表明，AM188的肾小管分泌涉及有机阴离子和阳离子转运系统。
