Erucylphosphocholine: pharmacokinetics, biodistribution and CNS-accumulation in the rat after intravenous administration View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

1999-10

AUTHORS

Bernhard Erdlenbruch, Verena Jendrossek, Angela Gerriets, Friedrich Vetterlein, Hansjörg Eibl, Max Lakomek

ABSTRACT

The clinical use of alkylphosphocholines (APC) in cancer patients is restricted because of the high gastrointestinal toxicity and the need for oral administration. Therefore we evaluated the clinical pharmacology of erucylphosphocholine (ErPC), the first derivative of the APC family suitable for intravenous administration with strong antineoplastic activity, in vitro and in vivo in rats. The pharmacokinetic parameters after a single intravenous dose of 40 mg/kg were calculated using a two-compartment model: C(max) = 1.6 +/- 0.3 micromol/ml, T(1/2alpha) = 0.18 +/- 0.09 h, T(1/2beta) = 3.3 +/- 0.88 h, clearance = 9.7 +/- 1.2 ml/h, AUC = 2.5 +/- 0.3 micromol/ml per h and Vss = 40.4 +/- 7.9 ml. Biodistribution studies were performed after repeated ErPC administration at different doses. Intravenous injections of 20 mg/kg given at intervals of 48 h for up to 4 weeks were well tolerated. Neither clinical evaluation nor laboratory parameters (haematology and clinical chemistry) revealed toxic side effects. In contrast, higher doses of ErPC (40 mg/kg per 48 h) led to weight loss. After 2 and 4 weeks of therapy with 20 mg/kg per 48 h a high ErPC accumulation was found in the adrenal glands, small intestine and brain. The brain to serum concentration ratios averaged 2.1 after 2 weeks and 4.5 after 4 weeks. Significant leucocytosis and thrombocytosis were observed after 4 weeks of ErPC treatment. The findings suggest that ErPC is a suitable candidate for clinical trials. In particular, owing to the high accumulation in brain tissue, ErPC is a potential agent for chemotherapy against malignant brain tumours. More... »

PAGES

484-490

References to SciGraph publications

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/s002800051122

DOI

http://dx.doi.org/10.1007/s002800051122

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1047462305

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/10550569


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