Fromm M F, Botsch S, Heinkele G, Evers J, Kroemer H K
Dr. Margarete Fischer-Bosch-Institut für Klinische Pharmakologie, Stuttgart, Germany.
Eur J Clin Pharmacol. 1995;48(3-4):279-83. doi: 10.1007/BF00198312.
The aim of this study was to investigate the disposition of propafenone and its Phase I and II metabolites in relation to kidney function under steady-state conditions. The mechanism of the renal handling of propafenone glucuronides (filtration, secretion) was also examined. Racemic (R/S) propafenone was administered to 7 young volunteers, to 5 older patients with a normal glomerular filtration rate and to 4 patients with chronic renal failure. No difference was found in the plasma concentrations of propafenone and 5-hydroxypropafenone between the three groups. The propafenone glucuronide (PPFG) concentration was elevated in the older compared to the younger subjects (S-PPFG: 544 vs. 222 nmol.ml-1.mol-1; R-PPFG: 576 vs. 304 nmol.ml-1.mol-1). Although Glomerular filtration rate did not differ, the renal clearance of propafenone glucuronides was reduced in the former group, which could be attributed to their impaired renal secretion. A dramatic increase in propafenone glucuronide concentration was observed in the patients with renal failure (S-PPFG: 2783 nmol.ml-1.mol-1; R-PPFG: 7340 nmol.ml-1.mol-1). In summary, the disposition of propafenone and of its active metabolite 5-hydroxypropafenone was not affected by kidney dysfunction, indicating that no dose adjustment is necessary in patients with renal failure. The accumulation of drug glucuronides in older patients with apparently normal kidney function should be taken into account as a possible factor modifying drug therapy.
本研究的目的是在稳态条件下研究普罗帕酮及其Ⅰ相和Ⅱ相代谢产物与肾功能相关的处置情况。还研究了普罗帕酮葡糖醛酸苷的肾脏处理机制（滤过、分泌）。消旋（R/S）普罗帕酮分别给予7名年轻志愿者、5名肾小球滤过率正常的老年患者和4名慢性肾衰竭患者。三组之间普罗帕酮和5-羟基普罗帕酮的血浆浓度未发现差异。与年轻受试者相比，老年受试者中普罗帕酮葡糖醛酸苷（PPFG）浓度升高（S-PPFG：544 vs. 222 nmol·ml⁻¹·mol⁻¹；R-PPFG：576 vs. 304 nmol·ml⁻¹·mol⁻¹）。尽管肾小球滤过率无差异，但前一组中普罗帕酮葡糖醛酸苷的肾清除率降低，这可能归因于其肾脏分泌受损。肾衰竭患者中观察到普罗帕酮葡糖醛酸苷浓度急剧升高（S-PPFG：2783 nmol·ml⁻¹·mol⁻¹；R-PPFG：7340 nmol·ml⁻¹·mol⁻¹）。总之，普罗帕酮及其活性代谢产物5-羟基普罗帕酮的处置不受肾功能障碍的影响，表明肾衰竭患者无需调整剂量。在肾功能看似正常的老年患者中药物葡糖醛酸苷的蓄积应作为可能影响药物治疗的一个因素加以考虑。
