Depression of vitamin B6 levels due to gentamicin.
The renal toxicity of gentamicin is altered by dietary protein modifications, bicarbonate and acetazolamide administration, magnesium supplementation, polyaspartic acid, piperacillin, hypercalcemia and calcium channel blockers. Renal tissue gentamicin levels have an undetermined role. Reduction of renal pyridoxal 5'-phosphate (PLP- by gentamicin has been shown, as has protection from nephrotoxicity by administration of vitamin B6. To explore an interaction between gentamicin and vitamin B6, gentamicin (5 mg/kg) was given to rabbits by ip injection, with either pyridoxine (10 mg) or isovolemic saline for 3 weeks. There was not a difference between gentamicin levels for animals given gentamicin and pyridoxine versus those given gentamicin and saline. Gentamicin administration led to a 47% fall (p = .0001) in plasma PLP levels. Three days after the last gentamicin administration, the animals maintained a 32% decrease from the pre-gentamicin baseline values (p = 0.02). When pyridoxine was administered concurrently with gentamicin, the PLP rise of 49% was significant (p = 0.001). The mean level after the study (6%) was not significantly lower than baseline (p = .6). We believe that gentamicin interfers with vitamin B6 metabolism, but that vitamin B6 status does not affect levels of gentamicin. A number of drugs affect B6 levels, creating the potential for hypovitaminosis B6 to be an important mechanism of drug-drug interaction in seriously ill patients, particularly in sick newborns or the elderly with lower average PLP levels.
Weir
M R
MR
Department of Pediatrics, Madigan Army Medical Center, Tacoma, WA 98431-5406.
Keniston
R C
RC
Enriquez
J I
JI
McNamee
G A
GA
D000818:Animals; D001682:Biological Availability; D004032:Diet; D004347:Drug Interactions; D005839:Gentamicins / Q000097:blood / Q000494:pharmacology*; D007668:Kidney / Q000187:drug effects / Q000378:metabolism*; D009752:Nutritional Status / Q000187:drug effects*; D011736:Pyridoxine / Q000097:blood / Q000378:metabolism*; D011817:Rabbits; D026681:Vitamin B 6 Deficiency / Q000139:chemically induced*
D005839:Gentamicins; D011736:Pyridoxine