Kinetics of Nikkomycin Z Degradation in Aqueous Solution and in Plasma

• Published in: Biological & pharmaceutical bulletin Vol. 20; no. 5; pp. 577 - 580
• Main Authors: TOKUMURA, Tadakazu, HORIE, Toru
• Format: Journal Article
• Language: English
• Published: Tokyo The Pharmaceutical Society of Japan 01.05.1997; Maruzen; Japan Science and Technology Agency
• Subjects: Aminoglycosides; Animals; Anti-Bacterial Agents - blood; Anti-Bacterial Agents - pharmacokinetics; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antifungal agents; Antifungal Agents - blood; Antifungal Agents - pharmacokinetics; apparent first-order reaction; aqueous solution; Biological and medical sciences; Chromatography, High Pressure Liquid; Dogs; Drug Stability; Esterases - metabolism; Hydrogen-Ion Concentration; Male; Medical sciences; Mice; Mice, Inbred ICR; nikkomycin Z; Pharmacology. Drug treatments; plasma; Rabbits; Rats; Rats, Sprague-Dawley; Solutions; Species Specificity; stability; Rat; Liver; Rabbit; Variations; Esterases; Blood plasma; Degradation; Antifungal agent; Enzymatic activity; pH; Antiinfectious; Dog; Ungulata; Fissipedia; Carnivora; Enzyme; Digestive system; Interspecific comparison; Rodentia; Lagomorpha; Metabolism; In vitro; Pig; Vertebrata; Mammalia; Mouse; Animal; Hydrolases; Artiodactyla; Kinetics; Aqueous solution
• ISSN: 0918-6158; 1347-5215
• 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°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 (kobs) was 8.08×10-2h-1 (t1/2=8.6 h). The degradation rate of nikkomycin Z in dog plasma at 37°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 kobs values for rat, mouse, rabbit, and dog plasma at 37°C were 1.74×10-1min-1, 3.64×10-2 min-1, 5.10×10-1 h-1, and 6.14×10-2 h-1, respectively. The degradation rate of nikkomycin Z in rat plasma was remarkedly 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.