Statistical analysis of the adverse effects of glycopeptide antibiotics, based on pharmacokinetics and toxicokinetics (PK/TK).
The effects of vancomycin hydrochloride (VCM) and teicoplanin complex (TEIC) on hepatic function and renal function were evaluated in rats. VCM was injected via the jugular vein at doses of 40, 100, and 250 mg/kg, and TEIC was injected via the jugular vein at doses of 10, 30, 40, 50, and 60 mg/kg, both after being dissolved in 1 ml of saline solution. Increased doses of VCM significantly increased the integrated plasma concentrations, from 0 to 8 h, for blood urea nitrogen (BUN(0-8)) and serum creatinine (SCr(0-8)). TEIC gave rise to a slight increase in both BUN(0-8) and SCr(0-8) as its dose was increased. On the other hand, TEIC significantly increased the integrated plasma concentrations, from 0 to 8 h, for aspartate aminotransferase (AST(0-8)), and alanine aminotransferase (ALT(0-8)), at doses from 40 mg/kg to 60 mg/kg, though VCM did not increase these concentrations. This study suggests the importance of paying attention to hepatic function--in addition to renal function--when TEIC is administered to patients with methicillin-resistant Staphylococcus aureus (MRSA).
Yoshida
Makiko
M
Department of Pharmacy, Aoyama Second Hospital, Osaka, Japan.
Matzno
Sumio
S
Namba
Hiromi
H
Nishikata
Mayumi
M
Matsuyama
Kenji
K
D000410:Alanine Transaminase / Q000378:metabolism; D000818:Animals; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics* / Q000633:toxicity*; D001219:Aspartate Aminotransferases / Q000378:metabolism; D016002:Discriminant Analysis; D007668:Kidney / Q000187:drug effects; D007928:Lethal Dose 50; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D017334:Teicoplanin / Q000493:pharmacokinetics* / Q000633:toxicity*; D014640:Vancomycin / Q000493:pharmacokinetics* / Q000633:toxicity*
D000900:Anti-Bacterial Agents; D017334:Teicoplanin; D014640:Vancomycin; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase