トポテカン塩酸塩

0.8

0.91

Breast Feeding; Lactation; Antineoplastic Agents; Topoisomerase I Inhibitors

EMA approved medicines: Human medicine

EMA approved medicines: Human medicine

EMA approved medicines: Human medicine

213-218 °C

213 - 218 °C

Danger

H301 (18.8%): Toxic if swallowed [Danger Acute toxicity, oral]

P203, P261, P264, P264+P265, P270, P271, P280, P301+P316, P302+P352, P304+P340, P305+P351+P338, P318, P319, P321, P330, P332+P317, P337+P317, P362+P364, P403+P233, P405, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 48 reports by companies from 3 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Warning

H341: Suspected of causing genetic defects [Warning Germ cell mutagenicity]

The Approved Drug Products with Therapeutic Equivalence Evaluations identifies currently marketed prescription drug products, including topotecan hydrochloride, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act. /Topotecan hydrochloride/

Suitable extinguishing media: Use water spray, alcohol-resistant foam, dry chemical or carbon dioxide.

Advice for firefighters: Wear self contained breathing apparatus for fire fighting if necessary.

Store the vials protected from light in the original cartons at controlled room temperature between 20 deg and 25 °C (68 deg and 77 °F).

Conditions for safe storage, including any incompatibilities: Keep container tightly closed in a dry and well-ventilated place. Recommended storage temperature: -20 °C.

Accidental Release Measures. Personal precautions, protective equipment and emergency procedures: Use personal protective equipment. Avoid dust formation. Avoid breathing vapours, mist or gas. Ensure adequate ventilation. Evacuate personnel to safe areas. Avoid breathing dust. Environmental precautions: Prevent further leakage or spillage if safe to do so. Do not let product enter drains. Methods and materials for containment and cleaning up: Pick up and arrange disposal without creating dust. Sweep up and shovel. Keep in suitable, closed containers for disposal.

SRP: Expired or waste pharmaceuticals shall carefully take into consideration applicable DEA, EPA, and FDA regulations. It is not appropriate to dispose by flushing the pharmaceutical down the toilet or discarding to trash. If possible return the pharmaceutical to the manufacturer for proper disposal being careful to properly label and securely package the material. Alternatively, the waste pharmaceutical shall be labeled, securely packaged and transported by a state licensed medical waste contractor to dispose by burial in a licensed hazardous or toxic waste landfill or incinerator.

Waste treatment methods. Product: Offer surplus and non-recyclable solutions to a licensed disposal company. Contact a licensed professional waste disposal service to dispose of this material. Dissolve or mix the material with a combustible solvent and burn in a chemical incinerator equipped with an afterburner and scrubber. Contaminated packaging: Dispose of as unused product.

Precautions for safe handling: Avoid contact with skin and eyes. Avoid formation of dust and aerosols. Provide appropriate exhaust ventilation at places where dust is formed.

Appropriate engineering controls: Handle in accordance with good industrial hygiene and safety practice. Wash hands before breaks and at the end of workday.

Gloves must be inspected prior to use. Use proper glove removal technique (without touching glove's outer surface) to avoid skin contact with this product. Dispose of contaminated gloves after use in accordance with applicable laws and good laboratory practices. Wash and dry hands.

SRP: Local exhaust ventilation should be applied wherever there is an incidence of point source emissions or dispersion of regulated contaminants in the work area. Ventilation control of the contaminant as close to its point of generation is both the most economical and safest method to minimize personnel exposure to airborne contaminants. Ensure that the local ventilation moves the contaminant away from the worker.

Eye/face protection: Safety glasses with side-shields conforming to EN166 Use equipment for eye protection tested and approved under appropriate government standards such as NIOSH (US) or EN 166(EU).

Skin protection: Handle with gloves.

Body Protection: Impervious clothing. The type of protective equipment must be selected according to the concentration and amount of the dangerous substance at the specific workplace.

Respiratory protection: Where risk assessment shows air-purifying respirators are appropriate use a full-face particle respirator type N100 (US) or type P3 (EN 143) respirator cartridges as a backup to engineering controls. If the respirator is the sole means of protection, use a full-face supplied air respirator. Use respirators and components tested and approved under appropriate government standards such as NIOSH (US) or CEN (EU).

Topotecan is a substrate of the efflux transporters P-glycoprotein (Pgp, ABCB1) and ABCG2 (breast cancer resistance protein (BRCP)). Concomitant use of elacridar (not commercially available in the US), an inhibitor of both P-glycoprotein and ABCG2 transporters, with oral topotecan resulted in a 2.5-fold increase in the area under the plasma concentration-time curve (AUC) for both topotecan lactone, the pharmcologically active form of the drug, and total topotecan. Concomitant use of oral topotecan with inhibitors of P-glycoprotein (e.g., cyclosporine, ketoconazole, ritonavir, saquinavir) also resulted in substantial increases in topotecan exposure. In one study, concomitant use of cyclosporine administered within 4 hours of an oral dose of topotecan resulted in a 2- to 3-fold increase in the AUCs of both topotecan lactone and total topotecan. The manufacturer states that concomitant use of oral topotecan with Pgp inhibitors should be avoided. If topotecan is used concomitantly with a Pgp (ABCB1) and/or an ABCG2 inhibitor, careful monitoring for signs of toxicity should be performed.

Topotecan (TpT) is a major inhibitory compound of topoisomerase (topo) I that plays important roles in gene transcription and cell division. We have previously reported that heparin and heparan sulfate (HS) might be transported to the cell nucleus and they can interact with topoisomerase I. We hypothesized that heparin and HS might interfere with the action of TpT. To test this hypothesis we isolated topoisomerase I containing cell nuclear protein fractions from normal liver, liver cancer tissues, and hepatoma cell lines. The enzymatic activity of these extracts was measured in the presence of heparin, liver HS, and liver cancer HS. In addition, topo I activity, cell viability, and apoptosis of HepG2 and Hep3B cells were investigated after heparin and TpT treatments. Liver cancer HS inhibited topo I activity in vitro. Heparin treatment abrogated topo I enzyme activity in Hep3B cells, but not in HepG2 cells, where the basal activity was higher. Heparin protected the two hepatoma cell lines from TpT actions and decreased the rate of TpT induced S phase block and cell death. These results suggest that heparin and HS might interfere with the function of TpT in liver and liver cancer.

The severity of drug-induced myelosuppression may be increased when IV topotecan is used in combination with other cytotoxic agents, and dosage reduction may be necessary. Severe myelotoxicity, in some cases resulting in fatalities from sepsis, has occurred during combined therapy with IV topotecan and other antineoplastic agents (e.g., cisplatin, paclitaxel). A sequence-dependent interaction has been reported when IV topotecan is administered concomitantly with cisplatin; lower doses of each drug were required with administration of cisplatin on day 1 of the topotecan dosing schedule compared with administration of cisplatin on day 5 of the topotecan dosing schedule.

Concurrent administration of granulocyte colony-stimulating factor (G-CSF) can prolong the duration of neutropenia associated with IV topotecan therapy. If G-CSF (filgrastim) is to be used concomitantly, therapy should be initiated 24 hours after the final dose of IV topotecan (i.e., beginning on day 6 of the 21-day treatment course for monotherapy or beginning on day 4 of the 21-day treatment course for combination therapy with IV topotecan and cisplatin).

EXPERIMENTAL: In lactating rats receiving IV topotecan at a dosage of 4.72 mg/sq m, high concentrations of the drug (i.e., up to 48 times higher than plasma concentrations) were distributed into milk. It is not known whether topotecan is distributed into human milk.

IDENTIFICATION AND USE: Topotecan is antineoplastic medication acting as topoisomerase I inhibitor. HUMAN EXPOSURE AND TOXICITY: The dose-limiting toxicity of topotecan is leukopenia. Topotecan-induced neutropenia can cause neutropenic colitis. Fatalities due to neutropenic colitis have been reported in clinical trials with topotecan. Overdoses (up to 10-fold of the prescribed dose) occurred in patients treated with intravenous topotecan. The primary complication of overdosage is bone marrow suppression. Interstitial lung disease (sometimes fatal) has been reported during postmarketing experience with IV topotecan. Risk factors for developing interstitial lung disease include pulmonary fibrosis, lung cancer, exposure to thoracic radiation, use of drugs known to cause pulmonary toxicity, use of colony-stimulating factors (i.e., hematopoietic growth factors), and a history of interstitial lung disease. Patients should be monitored for symptoms suggestive of interstitial lung disease, including cough, fever, dyspnea, and/or hypoxia. Case report describes a patient with pre-existing pulmonary fibrosis and progressive extensive stage small cell lung cancer. After receiving a single intravenous dose of topotecan, the patient developed sub-acute respiratory failure, and died 15 days later with pathology findings of organizing, reparative phase, diffuse alveolar damage. Topotecan was clastogenic to cultured human lymphocytes with and without metabolic activation. ANIMAL STUDIES: Single dose toxicity was investigated in rodents and dogs following intravenous administration of topotecan. Doses of 56, 148 or 74 mg/ sq m were lethal in mice, rats or dogs respectively. Target organs of toxicity were bone marrow, lymphoid tissues, gastrointestinal tract and ovaries. In repeat dose experiments at or below the maximum tolerated dose, the toxicity profile was characterized by myelotoxicity (neutropenia, thrombocytopenia, lymphopenia and anemia), lymphoid depletion and gastrointestinal effects. Furthermore, other tissues with a rapid cell turnover, such as hair follicles and testis were affected. The main dose-limiting toxicity was the effect on bone marrow. In surviving animals, effects were reversible after termination of treatment. In mice, a single treatment with a cytotoxic agent causes cognitive impairment. Studies in dogs given about 1/4th the clinical dose of the drug daily for a month suggest that treatment may cause an increase in the incidence of multinucleated spermatogonial giant cells in the testes. Topotecan given to female rats prior to mating at a dose equal to the clinical dose caused superovulation possibly related to inhibition of follicular atresia. This dose given to pregnant female rats also caused increased pre-implantation loss. Topotecan was mutagenic to L5178Y mouse lymphoma cells with and without metabolic activation. It was also clastogenic to mouse bone marrow. Topotecan did not cause mutations in bacterial cells. Topotecan is also a germ cell mutagen and its effect is more pronounced during the post-meiotic stages through a mechanism that may involve increases in DNA oxidative stress.

/SIGNS AND SYMPTOMS/ Topotecan-induced neutropenia can cause neutropenic colitis (cecitis or typhlitis). Fatalities due to neutropenic colitis have been reported in clinical trials with topotecan. In patients presenting with fever, neutropenia, and a compatible pattern of abdominal pain, the possibility of neutropenic colitis should be considered.

/SIGNS AND SYMPTOMS/ Overdoses (up to 10-fold of the prescribed dose) occurred in patients treated with intravenous topotecan. The primary complication of overdosage is bone marrow suppression. The observed signs and symptoms of overdose are consistent with the known adverse reactions associated with Hycamtin for intravenous use. In addition, elevated hepatic enzymes and mucositis have been reported following overdose.

/SIGNS AND SYMPTOMS/ Interstitial lung disease (sometimes fatal) has been reported during postmarketing experience with IV topotecan. Risk factors for developing interstitial lung disease include pulmonary fibrosis, lung cancer, exposure to thoracic radiation, use of drugs known to cause pulmonary toxicity, use of colony-stimulating factors (i.e., hematopoietic growth factors), and a history of interstitial lung disease. Patients should be monitored for symptoms suggestive of interstitial lung disease, including cough, fever, dyspnea, and/or hypoxia. If a new diagnosis of interstitial lung disease is confirmed, the manufacturer states that topotecan therapy should be discontinued.

/CASE REPORTS/ Drug-induced pulmonary toxicities of anticancer agents have been well described, but the pathophysiology of agents typically used in advanced disease has not been well studied. Symptoms of pulmonary drug toxicity in advanced lung cancer patients may frequently be attributed to disease progression, pulmonary embolism, or infection. In patients with pre-existing interstitial pulmonary fibrosis even less is known. This report describes an unfortunate patient with pre-existing pulmonary fibrosis and progressive extensive stage small cell lung cancer. After receiving a single intravenous dose of topotecan, the patient developed sub-acute respiratory failure, and died 15 days later with pathology findings of organizing, reparative phase, diffuse alveolar damage. To our knowledge this is the first pathology confirmation of diffuse alveolar damage in a patient developing dyspnea following topotecan therapy. The frequency with which camptothecin-related dyspnea is associated with diffuse alveolar damage might be underestimated and is of special concern in patients with limited pulmonary reserve.

For more Human Toxicity Excerpts (Complete) data for Topotecan (6 total), please visit the HSDB record page.

Drug-Induced Liver Injury Severity and Toxicity (DILIst)

topotecan

DILI Negative

Oral

DOI:10.1016/j.drudis.2019.09.022

/LABORATORY ANIMALS: Acute Exposure/ Single dose toxicity was investigated in rodents and dogs following intravenous administration of topotecan. Doses of 56, 148 or 74 mg/sq m were lethal in mice, rats or dogs respectively. Target organs of toxicity were bone marrow, lymphoid tissues, gastrointestinal tract and ovaries.

/LABORATORY ANIMALS: Subchronic or Prechronic Exposure/ Repeat dose toxicity following intravenous administration of topotecan was studied in mice (5 days study), as well as in rats and dogs (5-28 days studies). In addition, rats were administered topotecan by the oral route during 6 months. All species showed signs of toxicity consistent with the pharmacological effects of topotecan. At or below the maximum tolerated dose (MTD, being 4.7 mg/sq m/day in rats and 1.3 mg/sq m/day in dogs), the toxicity profile was characterised by myelotoxicity (neutropenia, thrombocytopenia, lymphopenia and anemia), lymphoid depletion and gastrointestinal effects. Furthermore, other tissues with a rapid cell turnover, such as hair follicles and testis were affected. The main dose-limiting toxicity was the effect on bone marrow. In surviving animals, effects were reversible after termination of treatment. The available animal data do not indicate a potential for toxicity in major organs other than expected.

/LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ Studies in dogs given 0.4 mg/sq m IV (about 1/4th the clinical dose on a mg/sq m basis) of topotecan daily for a month suggest that treatment may cause an increase in the incidence of multinucleated spermatogonial giant cells in the testes.

/LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ Topotecan given to female rats prior to mating at a dose of 1.4 mg/sq m IV (about equal to the clinical dose on a mg/sq m basis) caused superovulation possibly related to inhibition of follicular atresia. This dose given to pregnant female rats also caused increased pre-implantation loss.

For more Non-Human Toxicity Excerpts (Complete) data for Topotecan (7 total), please visit the HSDB record page.

Because elimination of oral and IV topotecan may be prolonged in patients with renal impairment and geriatric patients may have decreased renal function, the risk of adverse effects may be greater in such patients. Careful dosage selection and monitoring of renal function are advised in geriatric patients receiving topotecan.

... In patients with pre-existing interstitial pulmonary fibrosis even less is known. This report describes an unfortunate patient with pre-existing pulmonary fibrosis and progressive extensive stage small cell lung cancer. After receiving a single intravenous dose of topotecan, the patient developed sub-acute respiratory failure, and died 15 days later with pathology findings of organizing, reparative phase, diffuse alveolar damage. To our knowledge this is the first pathology confirmation of diffuse alveolar damage in a patient developing dyspnea following topotecan therapy. The frequency with which camptothecin-related dyspnea is associated with diffuse alveolar damage might be underestimated and is of special concern in patients with limited pulmonary reserve.

Topotecan can cause fetal toxicity when administered to pregnant women. If the drug is administered during pregnancy or if the patient becomes pregnant while receiving the drug, the patient should be informed of the potential hazard to the fetus. The manufacturer states that use of oral topotecan is contraindicated in pregnant and nursing women.

Hycamtin is contraindicated in patients who have a history of severe hypersensitivity reactions (e.g., anaphylactoid reactions) to topotecan or to any of its ingredients. Hycamtin should not be used in patients with severe bone marrow depression.

Myelosuppression, principally neutropenia, is the dose-limiting toxicity of topotecan, and use of the drug is contraindicated in patients with severe myelosuppression. Oral and IV topotecan therapy should not be initiated in patients with baseline neutrophil counts less than 1500/cu mm or platelet counts less than 100,000/cu mm.

Emergency and supportive measures. 1. Maintain an open airway and assist ventilation if necessary. 2. Treat coma, seizures, hypotension, and arrhythmias if they occur. 3. Treat nausea and vomiting with ondansetron or metoclopramide. Consider adding a benzodiazepine. Treat fluid losses caused by gastroenteritis with IV crystalloid fluids. 4. Bone marrow depression should be treated with the assistance of an experienced hematologist or oncologist. Transfusions of packed red blood cells and platelets may be needed for episodes of bleeding. Recombinant erythropoietin may be useful for severe anemia, and hematopoietic colony-stimulating factors may be useful for neutropenia. ... /Antineoplastics/

Decontamination. Administer activated charcoal orally if conditions are appropriate. Gastric lavage is not necessary after small to moderate ingestions if activated charcoal can be given promptly. /Antineoplastics/

Enhanced elimination. Because of the rapid intracellular incorporation of most of these agents, dialysis and other extracorporeal removal procedures are generally not effective ... . /Antineoplastic/

/SRP:/ Immediate first aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR if necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on the left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Poisons A and B/

For more Antidote and Emergency Treatment (Complete) data for Topotecan (6 total), please visit the HSDB record page.

The Approved Drug Products with Therapeutic Equivalence Evaluations identifies currently marketed prescription drug products, including topotecan hydrochloride, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act. /Topotecan hydrochloride/

L01XX17

L - Antineoplastic and immunomodulating agents

QL - Antineoplastic and immunomodulating agents

Topotecan, a semi-synthetic derivative of camptothecin (a plant alkaloid obtained from the <i>Camptotheca acuminata</i> tree), is an anti-tumor drug with topoisomerase I-inhibitory activity similar to irinotecan. DNA topoisomerases are enzymes in the cell nucleus that regulate DNA topology (3-dimensional conformation) and facilitate nuclear processes such as DNA replication, recombination, and repair. During these processes, DNA topoisomerase I creates reversible single-stranded breaks in double-stranded DNA, allowing intact single DNA strands to pass through the break and relieve the topologic constraints inherent in supercoiled DNA. The 3'-DNA terminus of the broken DNA strand binds covalently with the topoisomerase enzyme to form a catalytic intermediate called a cleavable complex. After DNA is sufficiently relaxed and the strand passage reaction is complete, DNA topoisomerase reattaches the broken DNA strands to form the unaltered topoisomers that allow transcription to proceed. Topotecan interferes with the growth of cancer cells, which are eventually destroyed. Since the growth of normal cells can be affected by the medicine, other effects may also occur. Unlike irinotecan, topotecan is found predominantly in the inactive carboxylate form at neutral pH and it is not a prodrug.

Topotecan has the same mechanism of action as irinotecan and is believed to exert its cytotoxic effects during the S-phase of DNA synthesis. Topoisomerase I relieves torsional strain in DNA by inducing reversible single strand breaks. Topotecan binds to the topoisomerase I-DNA complex and prevents religation of these single strand breaks. This ternary complex interferes with the moving replication fork, which leads to the induction of replication arrest and lethal double-stranded breaks in DNA. As mammalian cells cannot efficiently repair these double strand breaks, the formation of this ternary complex eventually leads to apoptosis (programmed cell death). Topotecan mimics a DNA base pair and binds at the site of DNA cleavage by intercalating between the upstream (−1) and downstream (+1) base pairs. Intercalation displaces the downstream DNA, thus preventing religation of the cleaved strand. By specifically binding to the enzyme–substrate complex, Topotecan acts as an uncompetitive inhibitor.

Topoisomerase I relieves torsional strain in DNA by inducing reversible single-strand breaks. Topotecan binds to the topoisomerase I-DNA complex and prevents religation of these single-strand breaks. The cytotoxicity of topotecan is thought to be due to double-strand DNA damage produced during DNA synthesis, when replication enzymes interact with the ternary complex formed by topotecan, topoisomerase I, and DNA. Mammalian cells cannot efficiently repair these double strand breaks.

2-3 hours

The pharmacokinetics of topotecan have been evaluated in cancer patients following doses of 0.5 to 1.5 mg/sq m administered as a 30-minute infusion. Topotecan exhibits multiexponential pharmacokinetics with a terminal half-life of 2 to 3 hours.

Topotecan has a terminal half-life of 3-6 hours following oral administration and 2-3 hours following IV administration of the drug.

... The objective of this study was to characterize the disposition of topotecan in a patient with severe renal insufficiency receiving hemodialysis. ... The topotecan terminal half-life off dialysis was 13.6 hr, compared with an apparent half-life determined during hemodialysis of 3.0 hr. ...

Topotecan undergoes a reversible pH dependent hydrolysis of its lactone moiety; it is the lactone form that is pharmacologically active.

Topotecan undergoes a reversible pH-dependent hydrolysis of its lactone moiety; it is the lactone form that is pharmacologically active. At pH =4, the lactone is exclusively present, whereas the ring-opened hydroxy-acid form predominates at physiologic pH. In vitro studies in human liver microsomes indicate topotecan is metabolized to an N-demethylated metabolite. The mean metabolite:parent AUC ratio was about 3% for total topotecan and topotecan lactone following IV administration.

7M7YKX2N15

TOPOTECAN

Established Pharmacologic Class [EPC] - Topoisomerase Inhibitor

Mechanisms of Action [MoA] - Topoisomerase Inhibitors

Topotecan is a Topoisomerase Inhibitor. The mechanism of action of topotecan is as a Topoisomerase Inhibitor.

TOPOTECAN

Renal clearance is an important determinant of topotecan elimination. In a mass balance/excretion study in 4 patients with solid tumors, the overall recovery of total topotecan and its N-desmethyl metabolite in urine and feces over 9 days averaged 73.4 ± 2.3% of the administered IV dose. Fecal elimination of total topotecan accounted for 9 ± 3.6% while fecal elimination of N-desmethyl topotecan was 1.7 ± 0.6%.

The pharmacokinetics of topotecan have been extensively studied in patients with normal renal function and there is one study of patients with mild to moderate renal insufficiency. However, the effect of hemodialysis on topotecan disposition has not been reported. The objective of this study was to characterize the disposition of topotecan in a patient with severe renal insufficiency receiving hemodialysis. Topotecan lactone disposition was characterized in a patient on and off hemodialysis. The topotecan lactone clearance determined after administration of topotecan alone and with hemodialysis was 5.3 L/hr per sq m vs 20.1 L/hr per sq m respectively. At 30 min after the completion of hemodialysis, the topotecan plasma concentration obtained was greater than that measured at the end of hemodialysis (i.e. 8.0 ng/mL vs 4.9 ng/mL), suggesting a rebound effect. The topotecan terminal half-life off dialysis was 13.6 hr, compared with an apparent half-life determined during hemodialysis of 3.0 hr. These results demonstrate that topotecan plasma clearance while on hemodialysis increased approximately fourfold. Hemodialysis may be an effective systemic clearance process for topotecan and should be considered in selected clinical situations (e.g. inadvertent overdose, severe renal dysfunction).

In lactating rats receiving IV topotecan at a dosage of 4.72 mg/sq m, high concentrations of the drug (i.e., up to 48 times higher than plasma concentrations) were distributed into milk. It is not known whether topotecan is distributed into human milk.

Following oral administration, about 57% of topotecan (administered daily for 5 days) is excreted in urine as unchanged drug (20%) and as the N-desmethyl metabolite (2%).47 Approximately 33% of the oral dose of topotecan was eliminated in feces as total topotecan and approximately 2% as N-desmethyl topotecan. Following IV administration, about 74% of a topotecan dose is excreted, mostly unchanged in urine (51%) and feces (18%) within 9 days; excretion of N-desmethyl topotecan in urine is approximately 3% and in feces is approximately 2%. O-Glucuronide metabolites of topotecan and N-desmethyl topotecan also have been detected in urine following oral and IV (less than 2% of the administered IV dose) administration of the drug.

No substantial gender-related differences in pharmacokinetics were reported in patients receiving oral topotecan. The average plasma clearance of IV topotecan was 24% higher in males than in females, mainly because of difference in body size.

For more Absorption, Distribution and Excretion (Complete) data for Topotecan (6 total), please visit the HSDB record page.

MEDICATION

THERAPEUTIC CATEGORY: Antineoplastic

Topoisomerase I Inhibitors

Consumption (g per capita) in the USA (2002): 7.59e-07

Topotecan is semisynthetically manufactured from the plant-derived alkaloid camptothecin. The starting material may be obtained from two natural sources - Chinese (Acuminata) and Indian (Mappia). Purification of the crude extract from either source is required. The main steps in the synthesis involve reduction and selective oxidation of the quinoline moiety of camptothecin, followed by the introduction of an N,N-dimethylaminomethyl side-chain.

Preparation: J. C. Boehm et al., European Patent Office patent 321122,; eidem, United States of America patent 5004758 (1989, 1991 both to SmithKline Beecham).