Tokumura T, Horie T
Tsukuba Research Laboratories, Eisai Co., Ltd., Ibaraki, Japan.
Biol Pharm Bull. 1997 May;20(5):577-80. doi: 10.1248/bpb.20.577.
The stability of nikkomycin Z in aqueous solution at various pH values and in the plasma of several kinds of experimental animals was studied. The degradation of nikkomycin Z in aqueous solution at pH 4 to 11.5 and in plasma was an apparent first-order reaction. The degradation rate at 37 degrees C increased with increasing pH, from 4.0 to 7.5, and decreased with increasing pH from 7.5 to 10.2. Above pH 10.2, the degradation rate was constant. The maximal rate of nikkomycin Z degradation was observed in pH 7.5 buffer solution, in which the apparent first-order rate constant (k(obs)) was 8.08 x 10(-2) h(-1) (t1/2 = 8.6 h). The degradation rate of nikkomycin Z in dog plasma at 37 degrees C was the almost same as that in pH 7.5 buffer. The rates in rat, mouse, and rabbit plasma were much greater than that in pH 7.5 buffer; the k(obs) values for rat, mouse, rabbit, and dog plasma at 37 degrees C were 1.74 x 10(-1) min(-1), 3.64 x 10(-2) min(-1), 5.10 x 10(-1) h(-1), and 6.14 x 10(-2) h(-1), respectively. The degradation rate of nikkomycin Z in rat plasma was markedly decreased when NaF, an esterase inhibitor, was added to the plasma. The findings of faster degradation rates in rat, mouse, and rabbit plasma compared with that in pH 7.5 buffer were considered to be due to an esterase in the plasma. This notion was supported by results showing the degradation rate of nikkomycin Z in porcine liver esterase solution.
研究了多抗霉素Z在不同pH值的水溶液以及几种实验动物血浆中的稳定性。多抗霉素Z在pH值为4至11.5的水溶液及血浆中的降解为表观一级反应。在37℃时，降解速率随pH值从4.0升至7.5而增加，随pH值从7.5升至10.2而降低。在pH值高于10.2时，降解速率恒定。在pH 7.5缓冲溶液中观察到多抗霉素Z的最大降解速率，其中表观一级速率常数（k(obs)）为8.08×10⁻² h⁻¹（t1/2 = 8.6 h）。37℃时多抗霉素Z在犬血浆中的降解速率与在pH 7.5缓冲溶液中的几乎相同。在大鼠、小鼠和兔血浆中的降解速率远高于在pH 7.5缓冲溶液中的降解速率；37℃时大鼠、小鼠、兔和犬血浆的k(obs)值分别为1.74×10⁻¹ min⁻¹、3.64×10⁻² min⁻¹、5.10×10⁻¹ h⁻¹和6.14×10⁻² h⁻¹。当向大鼠血浆中添加酯酶抑制剂氟化钠时，多抗霉素Z在大鼠血浆中的降解速率显著降低。与pH 7.5缓冲溶液相比，大鼠、小鼠和兔血浆中降解速率更快的结果被认为是由于血浆中的酯酶所致。多抗霉素Z在猪肝酯酶溶液中的降解速率结果支持了这一观点。
