Idarubicin - Clinical Pharmacology
Data have suggested a significant inverse correlation between serum albumin concentration and free fraction of Etoposide. Etoposide, therefore, is cleared by both renal and nonrenal processes, i. The effect of renal disease on plasma Etoposide clearance is not known. It is also present in human plasma, presumably as the trans isomer.
In addition, 0-demethyulation of the dimethoxyphenol ring occurs through the CYP 3A4 isoenzyme pathway to produce the corresponding catechol. After intravenous infusion, the Cmax and AUC values exhibit marked intra- and inter-subject variability.
There is no evidence of a first-pass effect for Etoposide. For example, no correlation exists between the absolute oral bioavailability of Etoposide capsules and nonrenal clearance. No evidence exists for any other differences in Etoposide metabolism and excretion after administration of oral capsules as compared to intravenous infusion. In adults, the total body clearance of Etoposide is correlated with creatinine clearance, serum albumin concentration, and nonrenal clearance.
Patients with impaired renal function receiving Etoposide have exhibited reduced total body clearance, increased AUC and a lower volume of distribution at steady state. Use of cisplatin therapy is associated with reduced total body clearance. In children, elevated serum SGPT levels are associated with reduced drug total body clearance.
Prior use of cisplatin may also result in a decrease of Etoposide total body clearance in children. Although some minor differences in pharmacokinetic parameters between age and gender have been observed, these differences were not considered clinically significant. Etoposide injection in combination therapy with other approved chemotherapeutic agents in patients with refractory testicular tumors who have already received appropriate surgical, chemotherapeutic, and radiotherapeutic therapy.
Etoposide is contraindicated in patients who have demonstrated a previous hypersensitivity to Etoposide or any component of the formulation. Patients being treated with Etoposide must be frequently observed for myelosuppression both during and after therapy.
Myelosuppression resulting in death has been reported. Dose-limiting bone marrow suppression is the most significant toxicity associated with Etoposide therapy.
Therefore, the following studies should be obtained at the start of therapy and prior to each subsequent cycle of Etoposide: Physicians should be aware of the possible occurrence of an anaphylactic reaction manifested by chills, fever, tachycardia, bronchospasm, dyspnea, and hypotension. Higher rates of anaphylactic-like reactions have been reported in children who received infusions at concentrations higher than those recommended.
The role that concentration of infusion or rate of infusion plays in the development of anaphylactic-like reactions is uncertain. The infusion should be terminated immediately, followed by the administration of pressor agents, corticosteroids, antihistamines, or volume expanders at the discretion of the physician. For parenteral administration, Etoposide should be given only by slow intravenous infusion usually over a to minute period , since hypotension has been reported as a possible side effect of rapid intravenous injection.
Etoposide can cause fetal harm when administered to a pregnant woman. Etoposide has been shown to be teratogenic in mice and rats.
In rats, an intravenous Etoposide dose of 0. An IP dose of 1. Women of childbearing potential should be advised to avoid becoming pregnant.
If this drug is used during pregnancy, or if the patient becomes pregnant while receiving this drug, the patient should be apprised of the potential hazard to the fetus. Etoposide should be considered a potential carcinogen in humans. The occurrence of acute leukemia with or without a preleukemic phase has been reported in rare instances in patients treated with Etoposide alone or in association with other neoplastic agents. The risk of development of a preleukemic or leukemic syndrome is unclear.
Carcinogenicity tests with Etoposide have not been conducted in laboratory animals. In all instances where the use of Etoposide is considered for chemotherapy, the physician must evaluate the need and usefulness of the drug against the risk of adverse reactions. Most such adverse reactions are reversible if detected early. If severe reactions occur, the drug should be reduced in dosage or discontinued and appropriate corrective measures should be taken according to the clinical judgement of the physician.
Reinstitution of Etoposide therapy should be carried out with caution and with adequate consideration of the further need for the drug and alertness as to possible recurrence of toxicity. Periodic complete blood counts should be done during the course of Etoposide treatment. They should be performed prior to each cycle of therapy and at appropriate intervals during and after therapy.
At least one determination should be done prior to each dose of Etoposide. In patients with impaired renal function, the following initial dose modification should be considered based on measured creatinine clearance:. Subsequent Etoposide dosing should be based on patient tolerance and clinical effect.
Treatment of Swiss-Albino mice with 1. Maternal weight gain was not affected. Irreversible testicular atrophy was present in rats treated with Etoposide intravenously for 30 days at 0. It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from Etoposide, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.
From Wikipedia, the free encyclopedia. This article needs additional citations for verification. Please help improve this article by adding citations to reliable sources. Unsourced material may be challenged and removed. May Learn how and when to remove this template message. Rupp, Nazi Ideology Before The green and the brown: Harvard University Press, page Die okkulten Wurzeln des Nationalsozialismus.
An English translation of this essay is available. Nazi Conceptions of Christianity, — , , p. The Reich Food Corporation Reichsnahrstand , —". United States of America v. December 20, — April 14, Members of the Hitler Cabinet. Konstantin von Neurath Joachim von Ribbentrop. Wilhelm Frick Heinrich Himmler. Lutz Graf Schwerin von Krosigk. Werner von Blomberg Wilhelm Keitel. Minister for Food and Agriculture. Minister of Public Enlightenment and Propaganda. Minister for Science and Education.
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