Dieperink H, Kemp E, Leyssac P P, Starklint H, Wanscher M, Nielsen J, Jørgensen K A, Faber V, Flachs H
Clin Nephrol. 1986;25 Suppl 1:S137-43.
The effects of ketoconazole (Kcnz) on cyclosporine A (CyA) serum levels and CyA-nephrotoxicity were studied. To rats later anesthetized with pentobarbital sodium, CyA 12.5 and Kcnz 20 mg/kg/day (n = 20), or CyA 12.5 mg/kg and Kcnz-vehicle (n = 21), was dosed. To rats anesthetized with etomidate (n = 14), CyA 12.5 mg/kg and Kcnz-carrier was dosed. S-CyA was monitored during 14 days, and then the rats were investigated with clearance (C) methods (inulin [(in), lithium (Li)], sodium, and potassium), and liver (L) and kidney (K) CyA was measured. Kcnz increased S-CyA, L-CyA and K-CyA (+50 -80%). There were significant (p less than 0.05) correlations between S- and L- or K-CyA. Kcnz increased CyA nephrotoxicity: Mean Cin was 1.012 ml/min/gKW (kidney weight) after CyA treatment (a subnormal value), but decreased to 0.556 ml/min/gKW in the group also given Kcnz (p less than 0.001). CLi decreased from 0.135 to 0.048 ml/min/gKW (p less than 0.001), and absolute proximal tubular reabsorption decreased from 0.877 to 0.508 ml/min/gKW (p less than 0.001), while the fractional reabsorption in the proximal tubule (FPR), expressed as a percentage of GFR, increased from 86.9 to 91.6% (p less than 0.005). Thus, after Kcnz treatment to rats given CyA 12.5 mg/kg/day, their renal function was indistinguishable from that in rats given CyA 25 mg/kg/day.(ABSTRACT TRUNCATED AT 250 WORDS)
研究了酮康唑（Kcnz）对环孢素A（CyA）血清水平及CyA肾毒性的影响。给戊巴比妥钠麻醉后的大鼠分别给予CyA 12.5mg/kg及Kcnz 20mg/kg/天（n = 20），或CyA 12.5mg/kg及Kcnz溶媒（n = 21）。给依托咪酯麻醉的大鼠（n = 14）给予CyA 12.5mg/kg及Kcnz载体。在14天内监测血清CyA（S-CyA），然后用清除率（C）方法（菊粉[(in)、锂(Li)]、钠和钾）进行研究，并测定肝脏（L）和肾脏（K）中的CyA。Kcnz使S-CyA、L-CyA和K-CyA增加（+50 - 80%）。S-CyA与L-CyA或K-CyA之间存在显著（p<0.05）相关性。Kcnz增加了CyA肾毒性：CyA治疗后平均肌酐清除率（Cin）为1.012ml/min/gKW（肾脏重量，低于正常水平），但在同时给予Kcnz的组中降至0.556ml/min/gKW（p<0.001）。锂清除率（CLi）从0.135降至0.048ml/min/gKW（p<0.001），近端肾小管绝对重吸收从0.877降至0.508ml/min/gKW（p<0.001），而近端肾小管分数重吸收（FPR，以肾小球滤过率的百分比表示）从86.9%增至91.6%（p<0.005）。因此，给每天给予12.5mg/kg CyA的大鼠用Kcnz治疗后，其肾功能与每天给予25mg/kg CyA的大鼠无异。（摘要截短于250字）
