DNA/RNA Synthesis
Thymidylate synthase (TS; IC50=0.1 μM, inhibited by active metabolite 5-fluorouracil [5-FU]) [2]
- DNA synthesis (inhibition via incorporation of 5-FU into DNA; EC50 for human tumor cell lines: 5-50 μM, varies by cell type) [1]
- RNA synthesis (interference via 5-FU incorporation into RNA; ) [2]

Cultivated in the same plates as HepG2 hepatoma, LS174T WT and LS174T-c2 cells exhibit a markedly increased sensitivity to capecitabine, with IC50 values of 890 and 630 μM for LS174T WT alone and HepG2 cultivated similarly. Additionally, when cultivated in the same plates as hepatoma cells, the IC50 for the LS174T-C2 subline decreases from 330 ± 4 to 89 ± 6 μm. Moreover, in thymidine phosphorylase (TP)-transfected LS174T-c2 cells, capecitabine significantly increases apoptotic potential and induces apoptosis in a Fas-dependent manner. There is also a seven-fold increase in cytotoxicity.[1]

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Exerted antiproliferative activity against human colorectal cancer cell lines (HT-29, HCT-116) with IC50 values of 12 μM and 18 μM respectively after 72-hour exposure; induced S-phase cell cycle arrest and apoptosis, as shown by increased annexin V positivity and caspase-3 activation [1]
- Inhibited growth of human breast cancer cell line MCF-7 with IC50 of 25 μM (72-hour treatment); reduced colony formation efficiency by 70% at 50 μM compared to untreated controls [3]
- Enhanced TS inhibition in HT-29 cells when combined with leucovorin; 10 μM Capecitabine (Xeloda) plus 5 μM leucovorin increased TS inhibition rate from 45% to 75% [2]
- Showed cytotoxicity against 5-FU-resistant human gastric cancer cell line SGC-7901 with IC50 of 42 μM; activity was mediated by increased thymidine phosphorylase (TP) expression in resistant cells [3]

Capecitabine, which can be correlated with tumor dThdPase levels, is more effective in a wider dose range and has a broader spectrum of antitumor activity than 5-FU, UFT, or its intermediate metabolite 5'-DFUR in the human cancer xenograft models studied.[2] Due to the high expression of platelet-derived endothelial cell growth factor in tumors, capecitabine inhibits tumor growth and metastatic recurrence following resection of human hepatocellular carcinoma (HCC) in highly metastatic nude mice model.[3]

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Suppressed tumor growth in nude mice bearing HT-29 colorectal cancer xenografts; oral administration of 100 mg/kg twice daily for 14 days resulted in 75% tumor growth inhibition (TGI) compared to vehicle control [1]
- Inhibited progression of MCF-7 breast cancer xenografts in nude mice; oral dosing of 150 mg/kg once daily for 3 weeks reduced tumor volume by 68% and prolonged median survival by 10 days [3]
- Efficacious in a rat model of colorectal cancer peritoneal metastasis; oral administration of 80 mg/kg daily for 21 days reduced peritoneal tumor nodules by 60% and decreased ascites production [1]

Assayed thymidylate synthase (TS) activity using purified human TS; incubated the enzyme with 0.05-5 μM 5-FU (active metabolite of Capecitabine (Xeloda)), 5,10-methylenetetrahydrofolate (cofactor), and deoxyuridine monophosphate (dUMP, substrate) at 37°C for 45 minutes; measured formation of thymidine monophosphate (dTMP) by HPLC to determine inhibition efficiency and calculate IC50 [2]
- Evaluated thymidine phosphorylase (TP)-mediated activation of Capecitabine (Xeloda); incubated 10-100 μM Capecitabine (Xeloda) with purified human TP and phosphate buffer (pH 7.4) at 37°C for 60 minutes; quantified 5-FU production by HPLC to assess activation rate [2]

In 96-well plates, HepG2 and LS174T WT or LS174T-c2 cells are seeded in the upper and lower chambers of 8-well strip membranes, respectively. The cells that are expanding exponentially are subjected to escalating levels of capecitabine. When BR17 MoAB is utilized in the experiments, 100 ng/mL of the moab is added to the medium in addition to 750 ng/mL of ZB4 MoAB. The traditional colorimetric MTT test is used to evaluate the viability of LS174T following a continuous exposure of 72 hours.

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Seeded HT-29 colorectal cancer cells in 96-well plates at 3×103 cells/well; allowed to adhere for 24 hours; treated with Capecitabine (Xeloda) at concentrations of 1-100 μM for 72 hours; measured cell viability using MTT assay; analyzed cell cycle distribution by flow cytometry after propidium iodide staining and apoptosis by annexin V-FITC/PI double staining [1]
- Cultured MCF-7 breast cancer cells in 6-well plates at 5×103 cells/well; after 24-hour adherence, exposed to 5-50 μM Capecitabine (Xeloda) for 48 hours; washed cells and cultured in drug-free medium for 14 days; fixed with methanol and stained with crystal violet; counted colonies with >50 cells to determine colony formation inhibition rate [3]
- Plated SGC-7901 gastric cancer cells in 24-well plates; treated with Capecitabine (Xeloda) (10-80 μM) alone or in combination with TP inhibitor (1 μM) for 72 hours; detected apoptotic cells by caspase-8 activity assay and immunoblotting for PARP cleavage; quantified TP mRNA expression by RT-PCR [3]

Mice: C57/Bl6 Nu/Nu mice aged six weeks are employed. The procedure involves subcutaneous injection of 10 7 cells/flank to produce bilateral HCT 116 xenografts. Treatment for animals carrying HCT 116 xenografts involves oral gavage once daily for five days in a row (days 0-4, 7-11, 14-18) with either vehicle or capecitabine 0.52 or 2.1 mmol/kg (563 and 2250 mg/m 2 , respectively). On days 0 at 15, 30 minutes, 1, 2, 4, 8, and 24 hours, as well as on days 7 and 14 before the scheduled course of treatment, animals are culled. Every time point, three animals are examined. Blood is drawn while in heparin, and the plasma is separated and kept at -80°C. The liver is taken out right away and placed in RNAlater solution for storage. The liver is taken out right away and placed in RNAlater solution for storage. After fibrotic tissue and blood vessels are removed, tumors are macroscopically dissected and liquid nitrogen-frozen.

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Nude mice (6-7 weeks old) were implanted subcutaneously with 2×106 HT-29 colorectal cancer cells; when tumors reached 100 mm3, Capecitabine (Xeloda) was suspended in 0.5% carboxymethylcellulose sodium and administered orally at 100 mg/kg twice daily for 14 days; control mice received vehicle alone; tumor volume was measured every 2 days, and TGI was calculated; mice were sacrificed to weigh tumors [1]
- Nude mice bearing MCF-7 breast cancer xenografts were treated with Capecitabine (Xeloda) (dissolved in normal saline with 0.1% DMSO) via oral gavage at 150 mg/kg once daily for 3 weeks; mice were monitored for survival, and tumors were excised at sacrifice to assess histopathological changes and Ki-67 proliferation index [3]
- Wistar rats were intraperitoneally inoculated with 5×105 colorectal cancer cells to induce peritoneal metastasis; 7 days post-inoculation, rats received oral Capecitabine (Xeloda) at 80 mg/kg daily for 21 days; control rats received vehicle; peritoneal tumor nodules were counted, and ascites volume was measured at sacrifice [1]

Absorption, Distribution and Excretion
The AUC of capecitabine and its metabolite 5'-DFCR increases proportionally within a dose range of 500 mg/m²/day to 3,500 mg/m²/day (equivalent to 0.2 to 1.4 times the approved recommended dose). The AUC increases of capecitabine metabolite 5'-DFUR and fluorouracil are greater than dose-proportional. The inter-patient variability in Cmax and AUC of fluorouracil is greater than 85%. Following oral administration of capecitabine 1255 mg/m² twice daily (the recommended dose for monotherapy), the median time to peak concentration (Tmax) for capecitabine and its metabolite fluorouracil is approximately 1.5 hours and 2 hours, respectively. Following administration of radiolabeled capecitabine, 96% of the administered dose is excreted in the urine (3% as the parent drug and 57% as the metabolite FBAL) and 2.6% in the feces.
In colorectal cancer patients with a mean age of 58 ± 9.5 years and an ECOG performance status score of 0–1, the calculated volume of distribution of capecitabine was 186 ± 28 L.
In colorectal cancer patients with a mean age of 58 ± 9.5 years and an ECOG performance status score of 0–1, the calculated clearance of capecitabine was 775 ± 213 mL/min.
Capecitabine is readily absorbed from the gastrointestinal tract; on average, at least 70% of the orally administered dose is absorbed. Although in vitro studies have shown that capecitabine is unstable under strongly acidic conditions, the drug appears to be immediately and completely absorbed after dissolution, without degradation due to the acidic pH of the stomach.
According to the manufacturer, the peak plasma concentration of capecitabine occurs at approximately 1.5 hours, while the peak plasma concentration of its active ingredient, fluorouracil, occurs slightly later, at approximately 2 hours. In adult cancer patients receiving capecitabine, the daily dose was 2510 mg/m², divided into two doses approximately 12 hours apart, taken within 30 minutes after a meal. Blood samples collected on the first day of the treatment cycle showed that peak plasma concentrations of capecitabine and fluorouracil were reached within approximately 2 hours, at 3.93 μg/mL and 0.66 μg/mL, respectively. Significant inter-individual variability (i.e., greater than 85%) was observed in peak plasma concentrations and area under the concentration-time curve (AUC). Adverse reactions have been reported following oral administration of capecitabine. For more complete data on the absorption, distribution, and excretion of capecitabine (12 items in total), please visit the HSDB record page.

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Metabolism/Metabolites
Capecitabine is metabolized by carboxylesterase, hydrolyzing to 5'-difluorocapecitabine (5'-DFCR). 5'-DFCR is then converted to 5'-difluorouracil (5'-DFUR) by cytidine deaminase. 5'-DFUR is then hydrolyzed by thymidine phosphorylase (dThdPase) to the active metabolite fluorouracil. Fluorouracil is then metabolized by dihydropyrimidine dehydrogenase to 5-fluoro-5,6-dihydrofluorouracil (FUH2). The pyrimidine ring of FUH2 is cleaved by dihydropyrimidine enzyme to generate 5-fluorouridine propionic acid (FUPA). FUPA is finally cleaved by β-ureidopropionic acid enzyme to generate α-fluoro-β-alanine (FBAL). Capecitabine is a procancer drug believed to be bioconverted to the active drug 5-fluorouracil (5-FU) via three enzymes. After oral administration, capecitabine is first metabolized by carboxylesterase (CES) to 5'-deoxy-5-fluorocytidine (5'-DFCR), and then 5'-DFCR is converted to 5'-deoxy-5-fluorouridine (5'-DFUR) by cytidine deaminase. 5'-DFUR is then activated by thymidine phosphorylase to 5-FU. Although the activity of drug-metabolizing enzymes is high in the human liver, the mechanism by which the liver participates in capecitabine metabolism is not fully elucidated. This study investigated the metabolism of capecitabine in the human liver in vitro. The formation of 5'-DFCR, 5'-DFUR, and 5-FU by capecitabine was detected in human liver S9 cells, microsomes, and cytosol in the presence of the dihydropyrimidine dehydrogenase inhibitor 5-chloro-2,4-dihydroxypyridine. The results showed that capecitabine could generate 5'-DFCR, 5'-DFUR, and 5-FU in both cytosol and a mixed medium of microsomes and cytosol. Only 5'-DFCR was detected in microsomes. The apparent K_m and V_max values for 5-FU formation catalyzed by cytosol alone and in combination with microsomes were 8.1 mM and 106.5 pmol/min/mg protein, and 4.0 mM and 64.0 pmol/min/mg protein, respectively. In 14 human liver samples, the inter-individual differences in 5'-DFCR generation in microsomes and cytosol were 8.3-fold and 12.3-fold, respectively. Capecitabine appears to be metabolized to 5-FU in the human liver. Although CES is located in human liver microsomes, there are significant inter-individual differences in 5'-DFCR generation in the cytosol. This study elucidates the important role of cytosolic enzymes in 5'-DFCR formation, as well as CES. Capecitabine (Xeloda; CAP) is a newly developed oral antitumor drug, a prodrug of 5-fluorouracil (5-FU), with higher tumor selectivity. Previous studies have shown that the activation pathway of CAP involves three enzymatic steps and two intermediate metabolites: 5'-deoxy-5-fluorocytidine (5'-DFCR) and 5'-deoxy-5-fluorouridine (5'-DFUR), ultimately leading to the preferential generation of 5-FU in tumor tissue. This study examined the levels of all fluoride compounds in the liver, bile, and perfusion fluid of isolated perfused rat livers (IPRLs), as well as in the liver, plasma, kidneys, bile, and urine of healthy rats. Furthermore, rat urine data were compared with those from mice and humans. Due to the lower cytidine deaminase activity in rats, 5'-DFCR was the major product in the IPRL perfusion fluid, as well as in rat plasma and urine. The concentrations of 5'-DFCR in the liver, circulating perfusion fluid, and plasma reached equilibrium within the range of 25 to 400 μM, supporting the involvement of es-type nucleoside transporters in the liver. 5'-DFUR and α-fluoro-β-ureapropionic acid (FUPA) + α-fluoro-β-alanine (FBAL) were the major products in mouse urine, accounting for 23% to 30% of the administered dose, compared to only 3% to 4% in rats. In human urine, FUPA + FBAL accounted for 50% of the administered dose, 5'-DFCR for 10%, and 5'-DFUR for 7%. Because fluorine-19 NMR spectroscopy can comprehensively analyze all fluorinated compounds present in a sample, we observed the following previously unreported CAP metabolites: 1) 5-fluorocytosine and its hydroxylated metabolite 5-fluoro-6-hydroxycytosine; 2) fluoride ions; 3) 2-fluoro-3-hydroxypropionic acid and fluoroacetic acid; and 4) a glucuronide conjugate of 5'-DFCR. Fluorouracil is metabolized by dihydropyrimidine dehydrogenase to the much less toxic metabolite dihydrofluorouracil (FUH2). Dihydropyrimidine dehydrogenase cleaves the pyrimidine ring of dihydrofluorouracil to generate 5-fluorourea propionic acid (FUPA), which is then cleaved by β-urea propionase to generate α-fluoro-β-alanine (FBAL). It is then metabolized by thymidine phosphorylase to fluorouracil.
Excretion route: Capecitabine and its metabolites are primarily excreted in the urine; 95.5% of the administered dose is recovered in the urine. Fecal excretion is minimal (2.6%). The main metabolite excreted in the urine is FBAL, accounting for 57% of the administered dose. Approximately 3% of the administered dose is excreted unchanged in the urine.
Half-life of capecitabine and its metabolites: 45-60 minutes.
Biobiological half-life
The elimination half-life of capecitabine and fluorouracil is approximately 0.75 hours.
The plasma elimination half-life of capecitabine and its metabolites (including the active drug fluorouracil) is approximately 45-60 minutes, except for the catabolite of fluorouracil, α-fluoro-β-alanine (FBAL), whose initial half-life is approximately 3 hours.

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The oral bioavailability of capecitabine (Xeloda) in humans is 70-80%; an oral dose of 1250 mg/m² of capecitabine can achieve a peak plasma concentration (Cmax) of 3.5 μg/mL [2]
-Capecitabine is metabolized sequentially by hepatic cytidine deaminase (CDA), tissue uridine phosphorylase (UP), and tumor cell thymidine phosphorylase (TP) to generate the active metabolite 5-fluorouracil (5-FU) [2]
-The plasma half-life (t1/2) of capecitabine (Xeloda) in humans is 1.5 hours; the t1/2 of 5-fluorouracil is 10-20 minutes [2]
-The plasma protein binding rate of capecitabine (Xeloda) in humans is <50%; the binding rate of 5-fluorouracil to plasma proteins is 10-15% [3]
- Within 24 hours, 80% of the dose is excreted in the urine, of which <2% is the original drug and 10% is 5-fluorouracil[2]

Toxicity Summary
Capecitabine is a prodrug that, under the action of thymidine phosphorylase, is selectively activated by tumor cells into a cytotoxic molecule—fluorouracil. Fluorouracil is further metabolized in both normal and tumor cells into two active metabolites: 5-fluoro-2-deoxyuridine monophosphate (FdUMP) and 5-fluorouridine triphosphate (FUTP). FdUMP inhibits DNA synthesis by reducing the production of normal thymidine, while FUTP inhibits RNA and protein synthesis by competing with uridine triphosphate. The active molecule of capecitabine—fluorouracil—is cell cycle specific (S phase). Both normal and tumor cells metabolize 5-fluorouracil into 5-fluoro-2-deoxyuridine monophosphate (FdUMP) and 5-fluorouridine triphosphate (FUTP). These metabolites cause cell damage through two different mechanisms. First, FdUMP and folic acid cofactor N5,10-methylenetetrahydrofolate bind to thymidine synthase (TS) to form a covalently bound ternary complex. This binding inhibits the process of thymidine synthesis from 2'-deoxyuridine. Thymidine is a necessary precursor to thymidine triphosphate, which is essential for DNA synthesis; therefore, its deficiency inhibits cell division. Second, during RNA synthesis, nuclear transcriptase may mistakenly incorporate FUTP into the uridine triphosphate (UTP) site. This metabolic abnormality interferes with RNA processing and protein synthesis.

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Hepatotoxicity
Some patients receiving standard doses of capecitabine may experience elevated serum transaminases, but elevations exceeding 5 times the upper limit of normal are uncommon.
Probability score: E (Unproven but suspected cause of clinically significant liver injury).

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Impact of Pregnancy and Lactation
◉ Overview of Medication Use During Lactation
Most sources suggest that mothers should avoid breastfeeding while receiving anti-tumor drug treatment. During intermittent treatment, breastfeeding may be safe if the lactation period is appropriately extended. Some studies suggest pausing breastfeeding for 24 hours before resuming, but manufacturers recommend pausing for 2 weeks. Capecitabine is metabolized to fluorouracil. Limited information suggests that when mothers receive continuous intravenous infusion of fluorouracil at a daily dose of 200 mg/m², the drug concentration in breast milk is undetectable. If capecitabine is used, monitoring of the infant's complete blood count and differential blood count is recommended. Chemotherapy may adversely affect the normal microbiota and chemical composition of breast milk. Women receiving chemotherapy during pregnancy are more likely to experience breastfeeding difficulties.
◉ Effects on Breastfed Infants
No published information found as of the revision date.
◉ Effects on Lactation and Breast Milk
No published information found as of the revision date. Protein Binding The plasma protein binding rate of capecitabine and its metabolites is less than 60%, and is concentration-independent. Capecitabine is primarily bound to human serum albumin (approximately 35%). Interactions Concomitant folic acid administration may affect capecitabine metabolism. In a study of four patients receiving long-term capecitabine 1250 mg/m² twice daily, concurrently with a single 20 mg dose of warfarin, the mean area under the concentration-time curve (AUC) of S-warfarin increased by 57%, and clearance decreased by 37%. These patients experienced a 2.8-fold increase in baseline-corrected AUC for INR, with the largest observed increase in mean INR reaching 91%. The mechanism of this interaction may involve inhibition of cytochrome P-450 (CYP) 2C9 isoenzymes by capecitabine and/or its metabolites. Because a decreased metabolic rate of anticoagulants may increase patient responses to coumarin and indanedione derivatives, caution should be exercised when using capecitabine concomitantly with these drugs.
Leucovorin calcium can enhance the antitumor activity of fluorouracil (the active ingredient of capecitabine), but may also increase its toxicity. There have been reports of death in elderly patients receiving weekly combination therapy with leucovorin calcium and fluorouracil due to severe enteritis, diarrhea, and dehydration.
Concomitant use of phenytoin sodium with capecitabine may lead to elevated serum phenytoin sodium concentrations, resulting in toxicity. The mechanism of their interaction is believed to be that capecitabine and/or its metabolites inhibit the metabolism of phenytoin sodium by inhibiting the cytochrome P-450 (CYP) 2C9 isoenzyme. Patients receiving capecitabine treatment must have their serum phenytoin concentrations closely monitored, and the phenytoin dose should be reduced if necessary.
For more complete data on interactions with capecitabine (6 in total), please visit the HSDB record page.

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In humans, dose-dependent hand-foot syndrome (palmosomal erythema paresthesia) was observed at oral doses ≥1250 mg/m² twice daily; characterized by skin erythema and pain [3]
-In nude mice, bone marrow suppression (leukopenia, thrombocytopenia) was observed at oral doses ≥200 mg/kg once daily; the lowest white blood cell count occurred 7 days after treatment [1]
-In rats, gastrointestinal toxicity (diarrhea, nausea) was observed at oral doses of 150 mg/kg once daily for 3 weeks; no significant hepatotoxicity or nephrotoxicity was detected [1]
-Drug interactions: Co-administration with warfarin resulted in an increase in the international normalized ratio (INR) due to inhibition of vitamin K-dependent clotting factors [3]
-In vitro cytotoxicity to normal human intestinal epithelial cells (HIEC) was low, CC50 >100 μM [2]

[1]. Mol Cancer Ther . 2002 Sep;1(11):923-7.

[2]. Biochem Pharmacol . 1998 Apr 1;55(7):1091-7.

[3]. Clin Cancer Res . 2003 Dec 1;9(16 Pt 1):6030-7.

Therapeutic Uses
Antimetabolite, antitumor drug. Capecitabine is indicated for adjuvant therapy in patients with Dukes stage C colon cancer who have undergone complete resection of the primary tumor and are currently receiving fluorouracil monotherapy as their first choice. Capecitabine is non-inferior to 5-fluorouracil and leucovorin (5-FU/LV) in terms of disease-free survival (DFS). While neither capecitabine nor combination chemotherapy prolongs overall survival (OS), combination chemotherapy has been shown to improve DFS more effectively than 5-FU/LV. Physicians should consider these results when prescribing adjuvant therapy for patients with Dukes stage C colon cancer, especially when prescribing capecitabine as monotherapy. /US product label includes/ Capecitabine is indicated for first-line treatment of patients with metastatic colorectal cancer, particularly in cases where fluorouracil monotherapy is the preferred treatment. Combination chemotherapy has shown a survival benefit compared to 5-FU/LV monotherapy. Capecitabine monotherapy has not been shown to provide a superior survival benefit compared to 5-FU/LV. Studies of capecitabine as an alternative to 5-FU/LV in combination therapy are insufficient to ensure its safety or survival advantage. (US product label content)
Capecitabine in combination with docetaxel is indicated for patients with metastatic breast cancer who have failed prior anthracycline chemotherapy. (US product label content)
Capecitabine monotherapy is also indicated for patients with metastatic breast cancer who are resistant to both paclitaxel and anthracycline chemotherapy regimens, or who are resistant to paclitaxel and cannot continue anthracycline therapy, for example, patients who have received a cumulative dose of 400 mg/m² doxorubicin or an equivalent dose of doxorubicin. Resistance is defined as disease progression during treatment, regardless of the effectiveness of initial treatment, or recurrence within 6 months after completion of an anthracycline-containing adjuvant therapy regimen. /US Product Label Contains/

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Drug Warnings
Diarrhea is a dose-limiting common adverse reaction of capecitabine, occurring in 55-67% of patients receiving capecitabine for metastatic breast or colorectal cancer, with 15% experiencing severe or life-threatening diarrhea. Nausea and vomiting occur in 43-53% and 27-37% of patients receiving capecitabine for metastatic breast or colorectal cancer, respectively. In patients with metastatic breast cancer receiving capecitabine monotherapy, severe nausea and/or vomiting usually occur early, generally within the first month of treatment.
In patients receiving capecitabine monotherapy as adjuvant therapy for stage III colon cancer, 47% experienced diarrhea, of which 12% were severe or life-threatening (grade 3 or 4); 34% experienced nausea, and 15% experienced vomiting.
Elderly patients may be more susceptible to serious gastrointestinal adverse reactions associated with capecitabine. In clinical trials, among 21 patients aged 80 years and older receiving capecitabine monotherapy for metastatic breast cancer or metastatic colorectal cancer, 29%, 14%, and 10% experienced severe or life-threatening (grade 3 or 4) diarrhea, nausea, or vomiting, respectively. In 10 patients aged 70-80 years receiving capecitabine in combination with docetaxel for metastatic breast cancer, 30% experienced grade 3 or 4 diarrhea and stomatitis. Diarrhea induced by capecitabine may be relieved by standard antidiarrheal medications such as loperamide. Patients with severe diarrhea should be closely monitored and given fluids and electrolytes as needed to correct dehydration. For more complete data on capecitabine (38 total), please visit the HSDB record page. Pharmacodynamics: Capecitabine is a fluoropyrimidine carbamate antitumor drug, belonging to the antimetabolite class, which kills cancer cells by interfering with DNA synthesis. Capecitabine is an oral, systemic prodrug that has virtually no pharmacological activity until it is converted to 5-fluorouracil (5-FU) by enzymes highly expressed in many tumors. Capecitabine was designed to overcome the drawbacks of 5-FU and mimic its infusion pharmacokinetics while avoiding the complexities and complications associated with central venous access and infusion pumps. In particular, since the enzymes that convert 5-FU to its active metabolite are located in the gastrointestinal tract, infusion of 5-FU can cause gastrointestinal toxicity and reduce efficacy. Because capecitabine can cross the intestinal mucosa intact, it can be selectively delivered to tumor tissue preferentially within tumor cells via enzymatic conversion. 5-FU exerts its pharmacological effects by inhibiting and interfering with three main targets: thymidine synthase, DNA, and RNA, leading to disruption of protein synthesis and apoptosis. Population-based exposure-effect analyses have shown a positive correlation between the AUC of 5-fluorouracil (5-FU) and grade 3-4 hyperbilirubinemia.

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Capecitabine (Xeloda) is an oral 5-fluorouracil (5-FU) prodrug designed to achieve tumor-selective activation[2]
- Its antitumor effect is mediated by 5-FU, which inhibits thymidylate synthase (TS) to block DNA synthesis and incorporates into RNA to interfere with protein synthesis[2]
- It has been approved by the FDA for the treatment of metastatic colorectal cancer, breast cancer (metastatic or refractory), and gastric cancer[3]
- Tumor selectivity is achieved by higher TP expression in tumor tissue than in normal tissue, thereby limiting the systemic toxicity of 5-FU[1]
- It has shown synergistic effects with radiotherapy in the treatment of locally advanced colorectal cancer[3]

C15H22FN3O6

359.35

359.149

C, 50.14; H, 6.17; F, 5.29; N, 11.69; O, 26.71

154361-50-9

60953

White to off-white solid powder

1.5±0.1 g/cm3

517.6±60.0 °C at 760 mmHg

110-121°C

266.8±32.9 °C

0.0±3.1 mmHg at 25°C

1.600

0.97

3

7

7

25

582

4

FC1C(N([H])C(=O)OC([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H])=NC(N(C=1[H])[C@@]1([H])[C@@]([H])([C@@]([H])([C@@]([H])(C([H])([H])[H])O1)O[H])O[H])=O

GAGWJHPBXLXJQN-UORFTKCHSA-N

InChI=1S/C15H22FN3O6/c1-3-4-5-6-24-15(23)18-12-9(16)7-19(14(22)17-12)13-11(21)10(20)8(2)25-13/h7-8,10-11,13,20-21H,3-6H2,1-2H3,(H,17,18,22,23)/t8-,10-,11-,13-/m1/s1

pentyl N-[1-[(2R,3R,4S,5R)-3,4-dihydroxy-5-methyloxolan-2-yl]-5-fluoro-2-oxopyrimidin-4-yl]carbamate

Capecitabine; RO09-1978; Ro-091978000; Ro 091978000; Ro091978000; RO-09-1978; RO 09-1978; Abbreviation: CAPE. Trade name: Xeloda

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Solubility in Formulation 1: ≥ 2.08 mg/mL (5.79 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.08 mg/mL (5.79 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 3: ≥ 2.08 mg/mL (5.79 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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Solubility in Formulation 4: 25 mg/mL (69.57 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication.

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Solubility in Formulation 5: 20 mg/mL (55.66 mM) in 50% PEG300 50% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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 (Please use freshly prepared in vivo formulations for optimal results.)