Pharmacokinetics of dacarbazine (DTIC) in pregnancy.

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Kantrowitz-Gordon I, Hays K, Kayode O, Kumar AR, Kaplan HG, Reid JM, Safgren SL, Ames MM, Easterling TR, Hebert MF

Pharmacokinetics of dacarbazine (DTIC) in pregnancy.

Cancer Chemother Pharmacol. 2018 Mar;81(3):455-460. doi: 10.1007/s00280-017-3511-6. Epub 2018 Jan 5.

PubMed ID

29305638 [ View in PubMed

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Abstract

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.

DrugBank Data that Cites this Article

Drug Enzymes

Drug	Enzyme	Kind	Organism	Pharmacological Action	Actions
Dacarbazine	Cytochrome P450 1A2	Protein	Humans	Unknown	Substrate	Details