Chemical: Drug
thiotepa

PharmGKB contains no dosing guidelines for this . To report known genotype-based dosing guidelines, or if you are interested in developing guidelines, click here.



PharmGKB contains no Clinical Variants that meet the highest level of criteria.

To see more Clinical Variants with lower levels of criteria, click the button at the bottom of the page.

Disclaimer: The PharmGKB's clinical annotations reflect expert consensus based on clinical evidence and peer-reviewed literature available at the time they are written and are intended only to assist clinicians in decision-making and to identify questions for further research. New evidence may have emerged since the time an annotation was submitted to the PharmGKB. The annotations are limited in scope and are not applicable to interventions or diseases that are not specifically identified.

The annotations do not account for individual variations among patients, and cannot be considered inclusive of all proper methods of care or exclusive of other treatments. It remains the responsibility of the health-care provider to determine the best course of treatment for a patient. Adherence to any guideline is voluntary, with the ultimate determination regarding its application to be made solely by the clinician and the patient. PharmGKB assumes no responsibility for any injury or damage to persons or property arising out of or related to any use of the PharmGKB clinical annotations, or for any errors or omissions.

? = Mouse-over for quick help

The table below contains information about pharmacogenomic variants on PharmGKB. Please follow the link in the "Variant" column for more information about a particular variant. Each link in the "Variant" column leads to the corresponding PharmGKB Variant Page. The Variant Page contains summary data, including PharmGKB manually curated information about variant-drug pairs based on individual PubMed publications. The PMIDs for these PubMed publications can be found on the Variant Page.

The tags in the first column of the table indicate what type of information can be found on the corresponding Variant Page.

Links in the "Gene" column lead to PharmGKB Gene Pages.

List of all variant annotations for thiotepa

Gene ? Variant?
(147)
Alternate Names ? Chemicals ? Alleles ?
(+ chr strand)
Function ? Amino Acid?
Translation
No VIP available CA VA
rs1138272 NC_000011.10:g.67586108C>T, NC_000011.9:g.67353579C>T, NG_012075.1:g.7514C>T, NM_000852.3:c.341C>T, NP_000843.1:p.Ala114Val, XM_005273958.1:c.338C>T, XP_005274015.1:p.Ala113Val, rs11553894, rs17434783, rs1799811, rs1804665, rs3202011, rs4134657, rs52800258, rs61323549
C > T
SNP
A114V
No VIP available No Clinical Annotations available VA
rs2228100 NC_000017.10:g.19642952G>C, NC_000017.11:g.19739639G>C, NG_012251.1:g.13795C>G, NM_000691.4:c.985C>G, NM_001135167.1:c.985C>G, NM_001135168.1:c.985C>G, NP_000682.3:p.Pro329Ala, NP_001128639.1:p.Pro329Ala, NP_001128640.1:p.Pro329Ala, XM_005256522.1:c.1336C>G, XM_005256523.1:c.1336C>G, XM_005256523.2:c.1336C>G, XM_005256524.1:c.1336C>G, XM_005256524.3:c.1336C>G, XM_005256525.1:c.1336C>G, XM_005256526.1:c.766C>G, XM_011523730.1:c.766C>G, XM_011523731.1:c.766C>G, XP_005256579.1:p.Pro446Ala, XP_005256580.1:p.Pro446Ala, XP_005256581.1:p.Pro446Ala, XP_005256582.1:p.Pro446Ala, XP_005256583.1:p.Pro256Ala, XP_011522032.1:p.Pro256Ala, XP_011522033.1:p.Pro256Ala, rs3744696, rs56956419
G > C
SNP
P329A
No VIP available CA VA
rs6151031 NC_000009.11:g.75568383_75568384insCTGGTGAGGAGAGAACC, NC_000009.12:g.72953467_72953468insCTGGTGAGGAGAGAACC, NG_012249.1:g.4586_4587insGGTTCTCTCCTCACCAG, NM_000689.4:c.-468_-467insGGTTCTCTCCTCACCAG, XM_005251800.1:c.-14-454_-14-453insGGTTCTCTCCTCACCAG, rs142856037
- > CTGGTGAGGAGAGAACC
indel
Alleles, Functions, and Amino Acid Translations are all sourced from dbSNP 147

Overview

Generic Names
Trade Names
Brand Mixture Names

PharmGKB Accession Id

PA451668

Type(s):

Drug

Description

N,N'N'triethylenethiophosphoramide (ThioTEPA) is a cancer chemotherapeutic member of the alkylating agent group, now in use for over 50 years. It is a stable derivative of N,N',N'' triethylenephosphoramide (TEPA). It is mostly used to treat breast cancer, ovarian cancer and bladder cancer. It is also used as conditioning for Bone marrow transplantation. Its main toxicity is myelosuppression.

Source: Drug Bank

Indication

ThioTEPA is used a as conditioning treatment prior to allogeneic or autologous haematopoietic progenitor cell transplantation (HPCT) in haematological diseases in adult and paediatric patients. Also, when high dose chemotherapy with HPCT support it is appropriate for the treatment of solid tumours in adult and paediatric patients.

Source: Drug Bank

Other Vocabularies

Information pulled from DrugBank has not been reviewed by PharmGKB.

Pharmacology, Interactions, and Contraindications

Mechanism of Action

The alkyl group is attached to the guanine base of DNA, at the number 7 nitrogen atom of the imidazole ring. They stop tumor growth by crosslinking guanine nucleobases in DNA double-helix strands, directly attacking DNA. This makes the strands unable to uncoil and separate. As this is necessary in DNA replication, the cells can no longer divide. These drugs act nonspecifically.

Source: Drug Bank

Pharmacology

The unstable nitrogen-carbon groups alkylate with DNA causing irrepairable DNA damage. They stop tumor growth by crosslinking guanine nucleobases in DNA double-helix strands, directly attacking DNA. This makes the strands unable to uncoil and separate. As this is necessary in DNA replication, the cells can no longer divide. These drugs act nonspecifically.

Source: Drug Bank

Absorption, Distribution, Metabolism, Elimination & Toxicity

Half-Life

1.5 to 4.1 hours

Source: Drug Bank

Route of Elimination

Urinary excretion of 14C-labeled thiotepa and metabolites in a 34-year old patient with metastatic carcinoma of the cecum who received a dose of 0.3 mg/kg intravenously was 63%.

Source: Drug Bank

Chemical Properties

Chemical Formula

C6H12N3PS

Source: Drug Bank

Isomeric SMILES

S=P(N1CC1)(N1CC1)N1CC1

Source: Drug Bank

Canonical SMILES

S=P(N1CC1)(N1CC1)N1CC1

Source: Drug Bank

Average Molecular Weight

189.218

Source: Drug Bank

Monoisotopic Molecular Weight

189.048954601

Source: Drug Bank

SMILES

S=P(N1CC1)(N1CC1)N1CC1

Source: Drug Bank

InChI String

InChI=1S/C6H12N3PS/c11-10(7-1-2-7,8-3-4-8)9-5-6-9/h1-6H2

Source: Drug Bank

Genes that are associated with this drug in PharmGKB's database based on (1) variant annotations, (2) literature review, (3) pathways or (4) information automatically retrieved from DrugBank, depending on the "evidence" and "source" listed below.

Curated Information ?

Drug Interactions

Interaction Description
fosphenytoin - thiotepa Possible increase in thiotepa levels (source: Drug Bank)
phenytoin - thiotepa Possible increase in thiotepa levels (source: Drug Bank)
phenytoin - thiotepa Possible increase in thiotepa levels (source: Drug Bank)
thiotepa - bupropion Thiotepa, a strong CYP2B6 inhibitor, may decrease the metabolism and clearance of Bupropion, a CYP2B6 substrate. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of Bupropion if Thiotepa is initiated, discontinued or dose changed. (source: Drug Bank)
thiotepa - cyclophosphamide Thiotepa, a strong CYP2B6 inhibitor, may decrease the metabolism and clearance of Cyclophosphamide, a CYP2B6 substrate. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of Cyclophosphamide if Thiotepa is initiated, discontinued or dose changed. (source: Drug Bank)
thiotepa - irinotecan Thiotepa, a strong CYP2B6 inhibitor, may decrease the metabolism and clearance of Irinotecan, a CYP2B6 substrate. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of Irinotecan if Thiotepa is initiated, discontinued or dose changed. (source: Drug Bank)
thiotepa - ketamine Thiotepa, a strong CYP2B6 inhibitor, may decrease the metabolism and clearance of Ketamine, a CYP2B6 substrate. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of Ketamine if Thiotepa is initiated, discontinued or dose changed. (source: Drug Bank)
thiotepa - natalizumab The immunosuppressant, Thiotepa, may increase the adverse effects of Natalizumab. Increased risk of Progressive Multifocal Leukoencephalopathy (PML) and other infections. Concurrent therapy should be avoided. (source: Drug Bank)
thiotepa - promethazine Thiotepa, a strong CYP2B6 inhibitor, may decrease the metabolism and clearance of Promethazine, a CYP2B6 substrate. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of Promethazine if Thiotepa is initiated, discontinued or dose changed. (source: Drug Bank)
thiotepa - selegiline Thiotepa, a strong CYP2B6 inhibitor, may decrease the metabolism and clearance of Selegiline, a CYP2B6 substrate. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of Selegiline if Thiotepa is initiated, discontinued or dose changed. (source: Drug Bank)
trastuzumab - thiotepa Trastuzumab may increase the risk of neutropenia and anemia. Monitor closely for signs and symptoms of adverse events. (source: Drug Bank)

Curated Information ?

Relationships from National Drug File - Reference Terminology (NDF-RT)

May Treat
Contraindicated With

Publications related to thiotepa: 7

No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
PharmGKB summary: very important pharmacogene information for CYP2B6. Pharmacogenetics and genomics. 2010. Thorn Caroline F, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Cyclophosphamide-metabolizing enzyme polymorphisms and survival outcomes after adjuvant chemotherapy for node-positive breast cancer: a retrospective cohort study. Breast cancer research : BCR. 2010. Gor Priya P, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Host genetic variants in the interleukin-6 promoter predict poor outcome in patients with estrogen receptor-positive, node-positive breast cancer. Cancer research. 2009. DeMichele Angela, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Polymorphisms of drug-metabolizing enzymes (GST, CYP2B6 and CYP3A) affect the pharmacokinetics of thiotepa and tepa. British journal of clinical pharmacology. 2009. Ekhart Corine, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Relations between polymorphisms in drug-metabolising enzymes and toxicity of chemotherapy with cyclophosphamide, thiotepa and carboplatin. Pharmacogenetics and genomics. 2008. Ekhart Corine, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Elevated plasma ferritin and busulfan pharmacodynamics during high-dose chemotherapy regimens in children with malignant solid tumors. Clinical pharmacology and therapeutics. 2007. Bouligand J, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Triethylenethiophosphoramide is a specific inhibitor of cytochrome P450 2B6: implications for cyclophosphamide metabolism. Drug metabolism and disposition: the biological fate of chemicals. 2002. Rae James M, et al. PubMed

LinkOuts

Web Resource:
Wikipedia
National Drug Code Directory:
55390-030-10
DrugBank:
DB04572
KEGG Compound:
C07641
KEGG Drug:
D00583
FDA Drug Label at DailyMed:
b4e6b9e3-1c09-410e-a4bf-1e844887a201

Clinical Trials

These are trials that mention thiotepa and are related to either pharmacogenetics or pharmacogenomics.

No trials loaded.

NURSA Datasets

provided by nursa.org

No NURSA datasets available.

Common Searches

Search PubMed
Search Medline Plus
Search PubChem
Search CTD

Sources for PharmGKB drug information: DrugBank, PubChem.