TY - JOUR
T1 - Pharmacokinetics of dacarbazine (DTIC) in pregnancy
AU - Kantrowitz-Gordon, Ira
AU - Hays, Karen
AU - Kayode, Olumide
AU - Kumar, Aditya R.
AU - Kaplan, Henry G.
AU - Reid, Joel M.
AU - Safgren, Stephanie L.
AU - Ames, Matthew M.
AU - Easterling, Thomas R.
AU - Hebert, Mary F.
N1 - Publisher Copyright:
© 2018, Springer-Verlag GmbH Germany, part of Springer Nature.
PY - 2018/3/1
Y1 - 2018/3/1
N2 - Purpose: The purpose of this report is to describe, for the first time, the pharmacokinetics of dacarbazine (DTIC) and its metabolites [5-[3-methyl-triazen-1-yl]-imidazole-4-carboxamide (MTIC), 5-[3-hydroxymethyl-3-methyl-triazen-1-yl]-imidazole-4-carboxamide (HMMTIC) and 5-aminoimidazole-4-carboxamide (AIC)] during pregnancy (n = 2) and postpartum (n = 1). Methods: Non-compartmental DTIC, MTIC, HMMTIC, and AIC pharmacokinetics (PK) were estimated in one case at 29 week gestation and 18 day postpartum and a second case at 32 week gestation, in women receiving DTIC in combination with doxorubicin, bleomycin, and vinblastine for treatment of Hodgkin’s lymphoma. Drug concentrations were measured by HPLC. Results: In the subject who completed both pregnancy and postpartum study days, DTIC area under the concentration–time curve (AUC) was 27% higher and metabolite AUCs were lower by 27% for HMMTIC, 38% for MTIC, and 83% of AIC during pregnancy compared to postpartum. At 7 and 9 year follow-up, both subjects were in remission of their Hodgkin’s lymphoma. Conclusions: Based on these two case reports, pregnancy appears to decrease the metabolism of the pro-drug dacarbazine, likely through inhibition of CYP1A2 activity. Lower concentrations of active metabolites and decreased efficacy may result, although both these subjects experienced long-term remission of their Hodgkin’s lymphoma.
AB - Purpose: The purpose of this report is to describe, for the first time, the pharmacokinetics of dacarbazine (DTIC) and its metabolites [5-[3-methyl-triazen-1-yl]-imidazole-4-carboxamide (MTIC), 5-[3-hydroxymethyl-3-methyl-triazen-1-yl]-imidazole-4-carboxamide (HMMTIC) and 5-aminoimidazole-4-carboxamide (AIC)] during pregnancy (n = 2) and postpartum (n = 1). Methods: Non-compartmental DTIC, MTIC, HMMTIC, and AIC pharmacokinetics (PK) were estimated in one case at 29 week gestation and 18 day postpartum and a second case at 32 week gestation, in women receiving DTIC in combination with doxorubicin, bleomycin, and vinblastine for treatment of Hodgkin’s lymphoma. Drug concentrations were measured by HPLC. Results: In the subject who completed both pregnancy and postpartum study days, DTIC area under the concentration–time curve (AUC) was 27% higher and metabolite AUCs were lower by 27% for HMMTIC, 38% for MTIC, and 83% of AIC during pregnancy compared to postpartum. At 7 and 9 year follow-up, both subjects were in remission of their Hodgkin’s lymphoma. Conclusions: Based on these two case reports, pregnancy appears to decrease the metabolism of the pro-drug dacarbazine, likely through inhibition of CYP1A2 activity. Lower concentrations of active metabolites and decreased efficacy may result, although both these subjects experienced long-term remission of their Hodgkin’s lymphoma.
KW - Dacarbazine
KW - Metabolites
KW - Pharmacokinetics
KW - Pregnancy
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U2 - 10.1007/s00280-017-3511-6
DO - 10.1007/s00280-017-3511-6
M3 - Article
C2 - 29305638
AN - SCOPUS:85040064936
SN - 0344-5704
VL - 81
SP - 455
EP - 460
JO - Cancer chemotherapy and pharmacology
JF - Cancer chemotherapy and pharmacology
IS - 3
ER -