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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1-6 |
| Number of pages | 6 |
| Journal | Cancer Chemotherapy and Pharmacology |
| DOIs | |
| State | Accepted/In press - Jan 5 2018 |
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Keywords
- Dacarbazine
- Metabolites
- Pharmacokinetics
- Pregnancy
ASJC Scopus subject areas
- Oncology
- Toxicology
- Pharmacology
- Cancer Research
- Pharmacology (medical)
Cite this
Pharmacokinetics of dacarbazine (DTIC) in pregnancy. / Kantrowitz-Gordon, Ira; Hays, Karen; Kayode, Olumide; Kumar, Aditya R.; Kaplan, Henry G.; Reid, Joel M; Safgren, Stephanie L.; Ames, Matthew M.; Easterling, Thomas R.; Hebert, Mary F.
In: Cancer Chemotherapy and Pharmacology, 05.01.2018, p. 1-6.Research output: Contribution to journal › Article
}
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.
PY - 2018/1/5
Y1 - 2018/1/5
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
UR - http://www.scopus.com/inward/record.url?scp=85040064936&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85040064936&partnerID=8YFLogxK
U2 - 10.1007/s00280-017-3511-6
DO - 10.1007/s00280-017-3511-6
M3 - Article
C2 - 29305638
AN - SCOPUS:85040064936
SP - 1
EP - 6
JO - Cancer Chemotherapy and Pharmacology
JF - Cancer Chemotherapy and Pharmacology
SN - 0344-5704
ER -