Evidence map›Paper›PMID 29305638›Full record

ArticleCancer chemotherapy and pharmacology2018

Pharmacokinetics of dacarbazine (DTIC) in pregnancy.

Ira Kantrowitz-Gordon, Karen Hays, Olumide Kayode, Aditya R Kumar, Henry G Kaplan, Joel M Reid, Stephanie L Safgren, Matthew M Ames, Thomas R Easterling, Mary F Hebert

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PubMed Full text at PMC Publisher
In one paragraph

Article in Cancer chemotherapy and pharmacology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
0.8field-weighted citation impact, top 24% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

4 citing papers in PubMed, 15 citations in OpenAlex.

  1. Article
  2. Review
  3. Review
  4. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 4 institutions in 1 country.

Ira Kantrowitz-GordonDepartment of Family and Child Nursing, University of Washington, 1959 NE Pacific Street, Seattle, WA, 98195, USA.
Karen HaysDepartment of Pharmacy, University of Washington, 1959 NE Pacific Street, Seattle, WA, 98195, USA.
Olumide KayodeCenter for Cancer Research, National Cancer Institute, 8560 Progress Drive, Fredrick, MD, 21702, USA.
Aditya R KumarDepartment of Pharmacy, University of Washington, 1959 NE Pacific Street, Seattle, WA, 98195, USA.
Henry G KaplanSwedish Cancer Institute, Swedish Medical Center, 1221 Madison St #500, Seattle, WA, 98104, USA.
Joel M ReidDepartment of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic Graduate School of Biomedical Sciences, 200 First St SW, Rochester, MN, 55905, USA.
Stephanie L SafgrenDepartment of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic Graduate School of Biomedical Sciences, 200 First St SW, Rochester, MN, 55905, USA.
Matthew M AmesDepartment of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic Graduate School of Biomedical Sciences, 200 First St SW, Rochester, MN, 55905, USA.
Thomas R EasterlingDepartment of Pharmacy, University of Washington, 1959 NE Pacific Street, Seattle, WA, 98195, USA.
Mary F HebertDepartment of Pharmacy, University of Washington, 1959 NE Pacific Street, Seattle, WA, 98195, USA. mhebert@u.washington.edu.
University of Washington · USMayo Clinic · USNational Cancer Institute · USSwedish Medical Center · US

Funding

Transform Dissemination and Implementation Science in CTSA ProgramsUL1TR002319 · NCATS · UNIVERSITY OF WASHINGTON · PI John K. Amory · 2017 to 2026
$100.0M
Institute of Translational Health SciencesUL1TR000423 · NCATS · UNIVERSITY OF WASHINGTON · PI DISIS, MARY L. · 2012 to 2016
$49.4M
UW Obstetric-Fetal Pharmacology Research UnitU10HD047892 · NICHD · UNIVERSITY OF WASHINGTON · PI EASTERLING, THOMAS R, HEBERT, MARY F · 2004 to 2014
$9.4M
NCATS NIH HHS UL1 TR000423NCATS NIH HHS UL1 TR002319NICHD NIH HHS U10 HD047892
6 · The paper itself

Abstract

purposeThe 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).

methodsNon-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.

resultsIn 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.

conclusionsBased 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.

Indexed as

DacarbazineHodgkin DiseasePregnancy Complications, NeoplasticAdministration, IntravenousAdultAntineoplastic Agents, AlkylatingAntineoplastic Combined Chemotherapy ProtocolsArea Under CurveBleomycinDoxorubicinDrug MonitoringFemaleHumansInfant, NewbornNeoplasm StagingPregnancy5-(3-hydroxymethyl-3-methyl-1-triazeno)imidazole-4-carboxamide5-(3-methyl-1-triazeno)imidazole-4-carboxamideAntineoplastic Agents, AlkylatingBleomycinDacarbazineDoxorubicinVinblastineDacarbazineMetabolitesPharmacokineticsPregnancy

Identifiers

PMID29305638
PMCPMC5828904
OpenAlexW2782535318

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.