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QuickView for Capecitabine (compound)

Summary
General Info

PubChem

PubChem Compound 10861706

Name:	capecitabine
PubChem Compound ID:	10861706
Molecular formula:	C₁₅H₂₂FN₃O₇
Molecular weight:	375.35 g/mol

DrugBank

Identification

Name:	capecitabine
Name (isomeric):	DB01101
Drug Type:	small molecule
Synonyms:	R340
Brand:	Xeloda
Category:	Antimetabolites, Prodrugs, Antimetabolites, Antineoplastic, Antineoplastic Agents
CAS number:	154361-50-9

Pharmacology

Indication:	For the treatment of patients with metastatic breast cancer resistant to both paclitaxel and an anthracycline-containing chemotherapy regimen. May also be used in combination with docetaxel for the treatment of metastatic breast cancer in patients who have failed to respond to, or recurred or relasped during or following anthracycline-containing chemotherapy. Capecitabine is used alone as an adjuvant therapy following the complete resection of primary tumor in patients with stage III colon cancer when monotherapy with fluroprymidine is preferred. The use or capecitabine in combination regimens for advanced gastric cancer is currently being investigated.
Pharmacology:	Capecitabine is a fluoropyrimidine carbamate with antineoplastic activity indicated for the treatment of metastatic breast cancer and colon cancer. It is an orally administered systemic prodrug that has little pharmacologic activity until it is converted to fluorouracil by enzymes that are expressed in higher concentrations in many tumors. Fluorour... show more » Capecitabine is a fluoropyrimidine carbamate with antineoplastic activity indicated for the treatment of metastatic breast cancer and colon cancer. It is an orally administered systemic prodrug that has little pharmacologic activity until it is converted to fluorouracil by enzymes that are expressed in higher concentrations in many tumors. Fluorouracil it then metabolized both normal and tumor cells to 5-fluoro-2′-deoxyuridine 5′-monophosphate (FdUMP) and 5-fluorouridine triphosphate (FUTP). show less «
Mechanism of Action:	Capecitabine is a prodrug that is selectively tumour-activated to its cytotoxic moiety, fluorouracil, by thymidine phosphorylase, an enzyme found in higher concentrations in many tumors compared to normal tissues or plasma. Fluorouracil is further metabolized to two active metabolites, 5-fluoro-2'-deoxyuridine 5'-monophosphate (FdUMP) and 5-fluorou... show more » Capecitabine is a prodrug that is selectively tumour-activated to its cytotoxic moiety, fluorouracil, by thymidine phosphorylase, an enzyme found in higher concentrations in many tumors compared to normal tissues or plasma. Fluorouracil is further metabolized to two active metabolites, 5-fluoro-2'-deoxyuridine 5'-monophosphate (FdUMP) and 5-fluorouridine triphosphate (FUTP), within normal and tumour cells. These metabolites cause cell injury by two different mechanisms. First, FdUMP and the folate cofactor, N5-10-methylenetetrahydrofolate, bind to thymidylate synthase (TS) to form a covalently bound ternary complex. This binding inhibits the formation of thymidylate from 2'-deaxyuridylate. Thymidylate is the necessary precursor of thymidine triphosphate, which is essential for the synthesis of DNA, therefore a deficiency of this compound can inhibit cell division. Secondly, nuclear transcriptional enzymes can mistakenly incorporate FUTP in place of uridine triphosphate (UTP) during the synthesis of RNA. This metabolic error can interfere with RNA processing and protein synthesis through the production of fraudulent RNA. show less «
Absorption:	Readily absorbed through the GI tract (~70%)
Protein binding:	< 60% (mainly albumin)
Biotransformation:	Metabolized by thymidine phosphorylase to fluoruracil.
Route of elimination:	Capecitabine and its metabolites are predominantly excreted in urine; 95.5% of administered capecitabine dose is recovered in urine. Fecal excretion is minimal (2.6%). The major metabolite excreted in urine is FBAL which represents 57% of the administered dose.About 3% of the administered dose is excreted in urine as unchanged drug.
Half Life:	45-60 minutes for capecitabine and its metabolites.
Affected organisms:	Humans and other mammals

Interactions

Food interaction:

Take 12 hours apart, within 30 minutes of the end of breakfast and dinner to reduce nausea.

Drug interaction:

Ethotoin	Capecitabine increases the effect of hydantoin
Acenocoumarol	Capecitabine may increase the anticoagulant effect of acenocoumarol by increasing its serum concentration.
Warfarin	Capecitabine may increase the serum concentration of warfarin by decreasing its metabolism. Monitor for changes in prothrombin time and therapeutic effects of warfarin if capecitabine is initiated or discontinued. Subsequent cycles of capecitabine may increase this effect.
Trimethoprim	The strong CYP2C9 inhibitor, Capecitabine, may decrease the metabolism and clearance of Trimethoprim, a CYP2C9 substrate. Consider alternate therapy or monitor for changes in therapeutic and adverse effects of Trimethoprim if Capecitabine is initiated, discontinued or dose changed.
Mephenytoin	Capecitabine increases the effect of hydantoin

Ethotoin	Capecitabine increases the effect of hydantoin
Acenocoumarol	Capecitabine may increase the anticoagulant effect of acenocoumarol by increasing its serum concentration.
Warfarin	Capecitabine may increase the serum concentration of warfarin by decreasing its metabolism. Monitor for changes in prothrombin time and therapeutic effects of warfarin if capecitabine is initiated or discontinued. Subsequent cycles of capecitabine may increase this effect.
Trimethoprim	The strong CYP2C9 inhibitor, Capecitabine, may decrease the metabolism and clearance of Trimethoprim, a CYP2C9 substrate. Consider alternate therapy or monitor for changes in therapeutic and adverse effects of Trimethoprim if Capecitabine is initiated, discontinued or dose changed.
Mephenytoin	Capecitabine increases the effect of hydantoin
Trastuzumab	Trastuzumab may increase the risk of neutropenia and anemia. Monitor closely for signs and symptoms of adverse events.
Zafirlukast	Capecitabine, a strong CYP2C9 inhibitor, may decrease the metabolism and clearance of zafirlukast. Consider alternate therapy or monitor for changes in zafirlukast therapeutic and adverse effects if capecitabine is initiated, discontinued or dose changed.
Dicumarol	Capecitabine may increase the anticoagulant effect of dicumarol by increasing its serum concentration.
Fosphenytoin	Capecitabine increases the effect of hydantoin
Anisindione	Capecitabine may increase the anticoagulant effect of anisindione by increasing its serum concentration.
Phenytoin	Capecitabine increases the effect of hydantoin
Tolbutamide	Capecitabine, a strong CYP2C9 inhibitor, may decrease the metabolism and clearance of Tolbutamide, a CYP2C9 substrate. Consider alternate therapy or monitor for changes in Tolbutamide therapeutic and adverse effects if Capecitabine is initiated, discontinued or dose changed.
Voriconazole	Capecitabine, a strong CYP2C9 inhibitor, may increase the serum concentration of voriconazole by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of voriconazole if capecitabine is initiated, discontinued or dose changed.
Torasemide	Capecitabine, a strong CYP2C9 inhibitor, may increase the serum concentration of Torasemide, a CYP2C9 substrate, by decreasing Torasemide metabolism and clearance. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of Torasemide if Capecitabine is initiated, discontinued or dose changed.
Tamoxifen	Capecitabine may reduce clearance rate of Tamoxifen. Monitor for changes in therapeutic/adverse effects of Tamoxifen if Capecitabine is initiated, discontinued or dose changed.

Targets

Enzymes

Thymidine phosphorylase

Catalyzes the reversible phosphorolysis of thymidine. The produced molecules are then utilized as carbon and energy sources or in the rescue of pyrimidine bases for nucleotide synthesis

UniProt ID:

P19971

Gene:

TYMP

Actions:

substrate

References:

de Bono JS, Twelves CJ: The oral fluorinated pyrimidines. Invest New Drugs. 2001;19(1):41-59.
View Article

Tsukamoto Y, Kato Y, Ura M, Horii I, Ishitsuka H, Kusuhara H, Sugiyama Y: A physiologically based pharmacokinetic analysis of capecitabine, a triple prodrug of 5-FU, in humans: the mechanism for tumor-selective accumulation of 5-FU. Pharm Res. 2001 Aug;18(8):1190-202.
View Article

Blanquicett C, Gillespie GY, Nabors LB, Miller CR, Bharara S, Buchsbaum DJ, Diasio RB, Johnson MR: Induction of thymidine phosphorylase in both irradiated and shielded, contralateral human U87MG glioma xenografts: implications for a dual modality treatment using capecitabine and irradiation. Mol Cancer Ther. 2002 Oct;1(12):1139-45.
View Article

Ishitsuka H, Shimma N, Horii I: [Discovery and development of novel anticancer drug capecitabine] Yakugaku Zasshi. 1999 Dec;119(12):881-97.
View Article

Ishitsuka H: Capecitabine: preclinical pharmacology studies. Invest New Drugs. 2000 Nov;18(4):343-54.
View Article

Endo M, Miwa M, Eda H, Ura M, Tanimura H, Ishikawa T, Miyazaki-Nose T, Hattori K, Shimma N, Yamada-Okabe H, Ishitsuka H: Augmentation of the antitumor activity of capecitabine by a tumor selective dihydropyrimidine dehydrogenase inhibitor, RO0094889. Int J Cancer. 2003 Sep 20;106(5):799-805.
View Article

Schuller J, Cassidy J, Dumont E, Roos B, Durston S, Banken L, Utoh M, Mori K, Weidekamm E, Reigner B: Preferential activation of capecitabine in tumor following oral administration to colorectal cancer patients. Cancer Chemother Pharmacol. 2000;45(4):291-7.
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Patel A, Pluim T, Helms A, Bauer A, Tuttle RM, Francis GL: Enzyme expression profiles suggest the novel tumor-activated fluoropyrimidine carbamate capecitabine (Xeloda) might be effective against papillary thyroid cancers of children and young adults. Cancer Chemother Pharmacol. 2004 May;53(5):409-14.
View Article

Eliason JF, Megyeri A: Potential for predicting toxicity and response of fluoropyrimidines in patients. Curr Drug Targets. 2004 May;5(4):383-8.
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Fischel JL, Ciccolini J, Formento P, Ferrero JM, Milano G: Synergistic cytotoxic interaction in hormone-refractory prostate cancer with the triple combination docetaxel-erlotinib and 5-fluoro-5'-deoxyuridine. Anticancer Drugs. 2006 Aug;17(7):807-13.
View Article

Walko CM, Lindley C: Capecitabine: a review. Clin Ther. 2005 Jan;27(1):23-44.
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Liver carboxylesterase 1

Dihydropyrimidine dehydrogenase [NADP+]

Involved in pyrimidine base degradation. Catalyzes the reduction of uracil and thymine. Also involved the degradation of the chemotherapeutic drug 5-fluorouracil

UniProt ID:

Q12882

Gene:

DPYD