Chrononephrotoxicity in rat of a vancomycin and gentamicin combination.
The effect of time of administration on excretion of two brush border enzymes--alanine aminopeptidase (AAP) and gamma-glutamyl transferase (gamma GT), and a lysosomal enzyme, N-acetyl-beta-D-glucosaminidase (NAG) with a single high dose of vancomycin, gentamicin or a combination of vancomycin and gentamicin was studied in male Wistar rats and compared with elimination of a control group. The rats received vancomycin intraperitoneally (200 mg.kg-1), gentamicin intramuscularly (100 mg.kg-1) or the combination of the drugs by the same route. A control group received isotonic NaCl solution. The four groups of animals received a single injection at 8 a.m., 2 p.m., 8 p.m., and 2 a.m. and urine excretion values for AAP, gamma GT and NAG were determined 24 hr later. The results show that the nephrotoxicity of gentamicin + vancomycin is greater than that observed with gentamicin, which again is greater than that observed with vancomycin. Furthermore, circadian variations in renal toxicity were observed, the least occurring at 8 a.m.
Institute of Xenobiotic Studies, Faculty of Pharmacy, Poitiers, France.
B
B
Fauconneau
E
E
De Lemos
C
C
Pariat
S
S
Bouquet
P
P
Courtois
A
A
Piriou
D000118:Acetylglucosaminidase / Q000652:urine; D000626:Aminopeptidases / Q000652:urine; D000818:Animals; D018826:CD13 Antigens; D002940:Circadian Rhythm / Q000187:drug effects; D003404:Creatinine / Q000652:urine; D004334:Drug Administration Schedule; D005839:Gentamicins / Q000633:toxicity*; D007273:Injections, Intramuscular; D007274:Injections, Intraperitoneal; D007687:Kidney Tubules, Proximal / Q000187:drug effects*; D008297:Male; D008871:Microvilli / Q000201:enzymology; D051381:Rats; D011919:Rats, Inbred Strains; D014640:Vancomycin / Q000633:toxicity*; D005723:gamma-Glutamyltransferase / Q000652:urine
D005839:Gentamicins; D014640:Vancomycin; D003404:Creatinine; D005723:gamma-Glutamyltransferase; D000118:Acetylglucosaminidase; D000626:Aminopeptidases; D018826:CD13 Antigens