The Experts below are selected from a list of 54 Experts worldwide ranked by ideXlab platform
Ilektra Athanasiadi - One of the best experts on this subject based on the ideXlab platform.
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Safety, tolerability and pharmakocinetic properties of the novel Triazene TriN 2755 in tumor bearing dogs
2020Co-Authors: Ilektra AthanasiadiAbstract:TriN 2755 is an Alkylating Antineoplastic Agent for intravenous (IV) use which carries the triazene group as cytotoxic principle. The purpose of the study was to determine the maximum tolerated dose (MTD), the dose limiting toxicity (DLT), and pharmacokinetic (PK) profile of TriN 2755 in tumor bearing dogs. Additionally, tumor response was monitored and assessed after chemotherapy as a secondary goal. Treatment schedule consisted of IV administration of the drug over 20 minutes on two consecutive weeks per month for a total of three cycles. Thirty tumor bearing dogs were included in the study. The starting dose was 25 mg/kg and the escalation steps occurred in increments of 20% of the previous dose. The MTD was 74.6 mg/kg. The DLT was characterized by gastrointestinal adverse events only. The pharmacokinetic of TriN 2755 and its main metabolites in plasma and sputum are described in a two compartment model. The response rate for 19/30 dogs was 47.3% (6 partial remission, 3 stable disease) and the median progression-free interval (PFI) for the responders was 47d (range 21-450d). In summary, this study demonstrated a safe and tolerable dose of TriN 2755 for IV use in tumor bearing dogs. The adverse events were mild in severity and limited only in fatigue and gastrointestinal upset. = TriN 2755 ist eine alkylierende, antineoplastische Substanz fur intravenose (IV) Verabreichung, das die Triazenegrouppe als zytotoxisches Prinzip tragt. Ziel dieser Studie war die Bestimmung der maximalen tolerierbaren Dosis (MTD), der Dosis-limitierenden Toxizitat (DLT) und des pharmakokinetischen Profils von TriN 2755 in Hunden mit Tumoren. Die Ansprache auf die Chemotherapie wurde zusatzlich als sekundares Ziel kontrolliert und bewertet. Der Behandlungsplan bestand aus der IV Verabreichung von TriN 2755 uber 20 Minuten an zwei aufeinanderfolgenden Wochen pro Monat fur drei Zyklen. Dreissig Hunden mit Tumoren wurden in die Studie eingeschlossen. Die Anfangsdosis war 25 mg/kg und die Eskalationsstufen erfolgten in 20%-Schritten der vorherigen Dosis. Die MTD war 74,6 mg/kg. Als dosis-limitierende Toxizitat wurden nur gastrointestinale Nebenwirkungen beobachtet. Die Pharmakokinetik von TriN 2755 und seinen Hauptmetaboliten im Plasma und Sputum sind in einem zwei Kompartiment-Modell beschrieben. Die Ansprache-Rate fur 19/30 Hunde erreichte 47,3% (6 partielle Remission und 3 stabile Erkrankung) und die mediane progressionsfreie Intervall fur die Hunde, die angesprochen haben, war 47 Tage (21-450 Tage). Zusammenfassend konnte in dieser Studie gezeigt werden, dass es nebenwirkungsarme, tolerierbare Dosis von TriN 2755 fur IV Verabreichung bei Hunden mit Tumoren gibt. Die Nebenwirkungen waren mild und selbstlimitierend, aus Mudigkeit und gastrointestinale Storungen bestehend.
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Safety, tolerability and pharmacokinetic properties of the novel triazene TriN 2755 in tumor bearing dogs
Veterinary and Comparative Oncology, 2015Co-Authors: Ilektra Athanasiadi, Caroline Geigy, Ralf A Hilger, V. Meier, Carla Rohrer BleyAbstract:TriN 2755 is an Alkylating Antineoplastic Agent for intravenous (IV) use, carrying the triazene group as the cytotoxic principal. Using a standard 3 + 3 design, a phase I study was performed in tumour bearing dogs to determine the maximum tolerated dose (MTD), the dose limiting toxicity (DLT), and pharmacokinetic (PK) profile of TriN 2755. Thirty dogs were included in the study. TriN 2755 was administered over 20 min on two consecutive weeks per month for a total of three cycles. The starting dose was 25 mg kg-1 and the MTD was 74.6 mg kg-1 . Three dogs experienced DLT, which was characterized by gastrointestinal adverse events. The PKs of TriN 2755 and its main metabolites in plasma and sputum are described in a two-compartment model. The response rate for 19 of 30 dogs was 47.3% (six partial remission, three stable disease) and the median progression-free interval (PFI) for the responders was 47 days (range: 21-450 days).
Carla Rohrer Bley - One of the best experts on this subject based on the ideXlab platform.
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Safety, tolerability and pharmacokinetic properties of the novel triazene TriN 2755 in tumor bearing dogs
Veterinary and Comparative Oncology, 2015Co-Authors: Ilektra Athanasiadi, Caroline Geigy, Ralf A Hilger, V. Meier, Carla Rohrer BleyAbstract:TriN 2755 is an Alkylating Antineoplastic Agent for intravenous (IV) use, carrying the triazene group as the cytotoxic principal. Using a standard 3 + 3 design, a phase I study was performed in tumour bearing dogs to determine the maximum tolerated dose (MTD), the dose limiting toxicity (DLT), and pharmacokinetic (PK) profile of TriN 2755. Thirty dogs were included in the study. TriN 2755 was administered over 20 min on two consecutive weeks per month for a total of three cycles. The starting dose was 25 mg kg-1 and the MTD was 74.6 mg kg-1 . Three dogs experienced DLT, which was characterized by gastrointestinal adverse events. The PKs of TriN 2755 and its main metabolites in plasma and sputum are described in a two-compartment model. The response rate for 19 of 30 dogs was 47.3% (six partial remission, three stable disease) and the median progression-free interval (PFI) for the responders was 47 days (range: 21-450 days).
Hoffmann H - One of the best experts on this subject based on the ideXlab platform.
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Influence of leukemia P388 on plasma concentration-time profiles of bendamustine in B6D2F1 mice.
Die Pharmazie, 1992Co-Authors: Amlacher R, Weber H, R. Preiss, Hoffmann HAbstract:: It was the aim of this study to investigate whether leukemia P388 being an important murine transplantation tumor may alter the plasma concentration-time profiles of the Alkylating Antineoplastic Agent bendamustine (1) in mice. In an advanced tumor stage the rapid decline of 1 plasma levels was found to be retarded in tumor-bearing in comparison to tumor-free animals both after i.v. and p.o. drug administration. These changes cannot be explained by the neoplasia-related depression of drug metabolism whereas the 1-containing ascitic fluid may be a possible reason for the prolonged drug levels in plasma. After p.o. administration of 1, the bioavailability of the drug was found to be increased in the leukemia-bearing animals.
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Pharmacokinetics of bendamustin (Cytostasan) in B6D2F1-mice
Die Pharmazie, 1991Co-Authors: Weber H, Amlacher R, R. Preiss, Hoffmann HAbstract:: The pharmacokinetics of bendamustine, (1; Cytostasan), an Alkylating Antineoplastic Agent of the N-lost group, was investigated in B6D2F1 mice. After i.v. injection of the maximally tolerated dose of 50 mg/kg a rapid decrease of the unchanged drug in plasma (MRT 21.9 min) and slowly decreasing levels of mono-, dihydroxy and beta-hydroxy-1 were observed. Variations of the age of the animals as well as of the dose administered did not alter the short MRT of 1. 1 is excreted via the kidneys to a considerable extent showing a similar metabolite pattern in urine as in plasma. The absorption of the drug from the gastrointestinal tract is incomplete resulting in an absolute bioavailability of about 40%.
Weber H - One of the best experts on this subject based on the ideXlab platform.
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Influence of leukemia P388 on plasma concentration-time profiles of bendamustine in B6D2F1 mice.
Die Pharmazie, 1992Co-Authors: Amlacher R, Weber H, R. Preiss, Hoffmann HAbstract:: It was the aim of this study to investigate whether leukemia P388 being an important murine transplantation tumor may alter the plasma concentration-time profiles of the Alkylating Antineoplastic Agent bendamustine (1) in mice. In an advanced tumor stage the rapid decline of 1 plasma levels was found to be retarded in tumor-bearing in comparison to tumor-free animals both after i.v. and p.o. drug administration. These changes cannot be explained by the neoplasia-related depression of drug metabolism whereas the 1-containing ascitic fluid may be a possible reason for the prolonged drug levels in plasma. After p.o. administration of 1, the bioavailability of the drug was found to be increased in the leukemia-bearing animals.
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Pharmacokinetics of bendamustin (Cytostasan) in B6D2F1-mice
Die Pharmazie, 1991Co-Authors: Weber H, Amlacher R, R. Preiss, Hoffmann HAbstract:: The pharmacokinetics of bendamustine, (1; Cytostasan), an Alkylating Antineoplastic Agent of the N-lost group, was investigated in B6D2F1 mice. After i.v. injection of the maximally tolerated dose of 50 mg/kg a rapid decrease of the unchanged drug in plasma (MRT 21.9 min) and slowly decreasing levels of mono-, dihydroxy and beta-hydroxy-1 were observed. Variations of the age of the animals as well as of the dose administered did not alter the short MRT of 1. 1 is excreted via the kidneys to a considerable extent showing a similar metabolite pattern in urine as in plasma. The absorption of the drug from the gastrointestinal tract is incomplete resulting in an absolute bioavailability of about 40%.
Amlacher R - One of the best experts on this subject based on the ideXlab platform.
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Influence of leukemia P388 on plasma concentration-time profiles of bendamustine in B6D2F1 mice.
Die Pharmazie, 1992Co-Authors: Amlacher R, Weber H, R. Preiss, Hoffmann HAbstract:: It was the aim of this study to investigate whether leukemia P388 being an important murine transplantation tumor may alter the plasma concentration-time profiles of the Alkylating Antineoplastic Agent bendamustine (1) in mice. In an advanced tumor stage the rapid decline of 1 plasma levels was found to be retarded in tumor-bearing in comparison to tumor-free animals both after i.v. and p.o. drug administration. These changes cannot be explained by the neoplasia-related depression of drug metabolism whereas the 1-containing ascitic fluid may be a possible reason for the prolonged drug levels in plasma. After p.o. administration of 1, the bioavailability of the drug was found to be increased in the leukemia-bearing animals.
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Pharmacokinetics of bendamustin (Cytostasan) in B6D2F1-mice
Die Pharmazie, 1991Co-Authors: Weber H, Amlacher R, R. Preiss, Hoffmann HAbstract:: The pharmacokinetics of bendamustine, (1; Cytostasan), an Alkylating Antineoplastic Agent of the N-lost group, was investigated in B6D2F1 mice. After i.v. injection of the maximally tolerated dose of 50 mg/kg a rapid decrease of the unchanged drug in plasma (MRT 21.9 min) and slowly decreasing levels of mono-, dihydroxy and beta-hydroxy-1 were observed. Variations of the age of the animals as well as of the dose administered did not alter the short MRT of 1. 1 is excreted via the kidneys to a considerable extent showing a similar metabolite pattern in urine as in plasma. The absorption of the drug from the gastrointestinal tract is incomplete resulting in an absolute bioavailability of about 40%.
