TY - JOUR
T1 - Trimethoprim: novel reactive intermediates and bioactivation pathways by cytochrome p450s
AU - Damsten, M.C.
AU - de Vlieger, J.S.B.
AU - Niessen, W.M.A.
AU - Irth, H.
AU - Vermeulen, N.P.E.
AU - Commandeur, J.N.M.
PY - 2008
Y1 - 2008
N2 - Trimethoprim (TMP) is a widely used antibacterial agent that is usually considered as a safe drug. TMP has, however, been implicated in rare adverse drug reactions (ADRs) in humans. Bioactivation to a reactive iminoquinone methide intermediate has been proposed as a possible cause for the toxicity of the drug. However, little is known about the cytochrome P450s (P450s) involved in this bioactivation and in the metabolism of TMP in general. In this study, we have investigated the metabolism and bioactivation of TMP by human liver microsomes (HLM) and rat liver microsomes, by recombinant human cytochrome P450s, and by the bacterial P450 BM3 mutant M11
AB - Trimethoprim (TMP) is a widely used antibacterial agent that is usually considered as a safe drug. TMP has, however, been implicated in rare adverse drug reactions (ADRs) in humans. Bioactivation to a reactive iminoquinone methide intermediate has been proposed as a possible cause for the toxicity of the drug. However, little is known about the cytochrome P450s (P450s) involved in this bioactivation and in the metabolism of TMP in general. In this study, we have investigated the metabolism and bioactivation of TMP by human liver microsomes (HLM) and rat liver microsomes, by recombinant human cytochrome P450s, and by the bacterial P450 BM3 mutant M11
UR - https://www.scopus.com/pages/publications/57449084682
UR - https://www.scopus.com/inward/citedby.url?scp=57449084682&partnerID=8YFLogxK
U2 - 10.1021/tx8002593
DO - 10.1021/tx8002593
M3 - Article
SN - 0893-228X
VL - 21
SP - 2181
EP - 2187
JO - Chemical Research in Toxicology
JF - Chemical Research in Toxicology
IS - 11
ER -
