PMID: 3754493Jan 1, 1986Paper

Comparison of the pharmacokinetics and protein binding of the anticancer drug, amsacrine and a new analogue, N-5-dimethyl-9-[(2-methoxy-4-methylsulfonylamino)phenyl-amino] -4-acridinecarboxamide in rabbits

Cancer Chemotherapy and Pharmacology
J W Paxton, J L Jurlina

Abstract

Amsacrine (NSC 249 992) is a new anticancer drug which, although effective for the treatment of various disseminated tumors, has shown disappointing activity against most solid tumors. A new analogue, N-5-dimethyl-9-[(2-methoxy-4-methylsulfonylamino)phenylamino] -4-acridine-carboxamide (CI-921, NSC 343 499) has been identified, which might offer a broader clinical antitumor spectrum. This analogue is more lipophilic (0.5 log p units) and is also a considerable weaker base (pKa 6.40) than amsacrine (pKa 7.43). This study compared the pharmacokinetics of total and unbound amsacrine and CI-921 in plasma after equimolar dose infusions (12.7 mumol/kg) in a balanced crossover design in six rabbits. Drug concentrations were determined by high-pressure liquid chromatography and the unbound fraction by equilibrium dialysis. Threefold higher total plasma concentrations were achieved with CI-921 than with amsacrine. However, the unbound fraction was significantly less for CI-921 (0.33% +/- 0.04) than for amsacrine (2.78% +/- 0.53). There was no significant difference between distribution and elimination half-life and mean residence time, but the apparent volume of distribution (means, 121 vs 45 l/kg) and clearance (means, 46.6 vs 16.3 l h...Continue Reading

References

Jan 1, 1985·Pharmacology·J W Paxton, J L Jurlina
Aug 1, 1974·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·B F Cain, G J Atwell
Jan 1, 1982·European Journal of Drug Metabolism and Pharmacokinetics·B VandelD Blum
Jul 1, 1982·Journal of Pharmaceutical Sciences·T W GuentertS Oie

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Citations

Jan 10, 2002·Journal of Pharmaceutical Sciences·Patrick Poulin, Frank-Peter Theil
Mar 30, 2016·International Journal of Pharmaceutics·Wenli ZhangZimei Wu
Jun 21, 2016·Critical Reviews in Oncology/hematology·Attia AfzalJianguo Sun
Jun 22, 2010·Regulatory Toxicology and Pharmacology : RTP·Ryuichi HasegawaAkihiko Hirose

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