Elevated plasma cysteinylglycine levels caused by cilastatin-associated antibiotic treatment.
Imipenem (thienamycin formamidine), a broad-spectrum beta-lactam antibiotic, is always used in combination with cilastatin in order to avoid the premature breakdown of imipenem by renal tubular dipeptidase. As this dipeptidase also hydrolyzes the glutathione metabolite cysteinylglycine, the therapeutic association of imipenem and cilastatin might cause an accumulation of the aminothiol cysteinylglycine. We demonstrate here that when patients are treated with imipenem-cilastatin, their plasma levels of cysteinylglycine are significantly and specifically increased, while cysteine levels are decreased and homocysteine levels are unaffected. We conclude that antibiotic treatment using imipenem-cilastatin induces important metabolic changes that should not remain unrecognized.
Badiou
Stéphanie
S
Department of Biochemistry, Intensive Care and Transplantation Unit (DAR B), University Hospital, Montpellier, France. s-badiou@chu-montpellier.fr
Bellet
Hélène
H
Lehmann
Sylvain
S
Cristol
Jean-Paul
JP
Jaber
Samir
S
D000900:Anti-Bacterial Agents / Q000009:adverse effects*; D015377:Cilastatin / Q000009:adverse effects*; D003545:Cysteine / Q000097:blood / Q000187:drug effects; D004150:Dipeptidases / Q000037:antagonists & inhibitors; D004151:Dipeptides / Q000097:blood* / Q000187:drug effects; D005260:Female; D006801:Humans; D015378:Imipenem / Q000009:adverse effects*; D007700:Kinetics; D008297:Male; D008875:Middle Aged
D000900:Anti-Bacterial Agents; D004151:Dipeptides; D015377:Cilastatin; C028505:cysteinylglycine; D015378:Imipenem; D004150:Dipeptidases; C038937:dipeptidase; D003545:Cysteine