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Effects of harringtonine in combination with acivicin, adriamycin, L-asparaginase, cytosine arabinoside, dexamethasone, fluorouracil or methotrexate on human acute myelogenous leukemia cell line KG-1 (1983)

Okano, Tsuyoshi ; Ohnuma, Takao ; Holland, James F. ; [et al.]

Springer

Investigational new drugs 1 (1983), S. 145-150

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ISSN: 1573-0646

Keywords: harringtonine ; combination chemotherapy

Source: Springer Online Journal Archives 1860-2000

Topics: Chemistry and Pharmacology , Medicine

Notes: Summary Harringtonine (HT) is a new antitumor agent reported to be active in patients with leukemia and lymphoma. The interaction of HT with various antitumor agents was studied in vitro using a human acute myelogenous leukemia cell line KG-1. For the analysis of the drug-drug interaction at the cellular level, Steel proposed the concept of an envelope of additivity. Using this concept, the effect of a two drug combination can be classified as supraadditive (enhancement of the effect), non-interactive (additive), subadditive, and protective (antagonistic). Combination of HT and cytosine arabinoside or HT and dexamethasone produced only additive effects. Combination of HT and methotrexate was subadditive. For HT plus adriamycin or HT plus 5-fluorouracil, data points indicated both subadditive and protective interaction. HT plus acivicin or HT plus L-asparaginase combinations were found to be protective of each other. None of the seven agents produced supraadditive interaction. These results may provide the basis for selecting sequential rather than concurrent combinations which include HT for the treatment of leukemia in man.

Type of Medium: Electronic Resource

URL: http://dx.doi.org/10.1007/BF00172073

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Quantification of homoharringtonine and harringtonine in serum by chemical ionization mass spectrometry (1982)

Robez, John ; Greaves, John ; Jui, Han ; [et al.]

Chichester : Wiley-Blackwell

Biological Mass Spectrometry 9 (1982), S. 510-514

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ISSN: 0306-042X

Keywords: Chemistry ; Analytical Chemistry and Spectroscopy

Source: Wiley InterScience Backfile Collection 1832-2000

Topics: Chemistry and Pharmacology

Notes: Homoharringtonine and harringtonine are esters of cephalotaxine and are naturally occurring alkaloids in certain coniferous trees in China. These compounds have been shown to have activity against certain types of leukemia in cell cultures, experimental animals, and initial clinical trials in China, and will undergo Phase I trials in several institutions. A gas chromatographic mass spectrometric technique was developed for the quantification of both drugs in serum. One drug serves as internal standard for the other. The drugs are extracted from serum with dichloromethane and are quantified by monitoring the protonated molecular ions of the trimethylsilyl derivatives obtained by chemical ionization (methane). Masses monitored are: m/z = 690 for homoharringtonine and m/z = 676 for harringtonine. Detection limit: 10 ng ml-1 (20 nmol); reproducibility: 1.6-15.0% in the 0-200 ng ml-1 range. Serum levels of harringtonine reached 145 ng mg-1 upon intraperitoneal injection of 3mg kg-1 in BDF-3 mice.

Additional Material: 6 Ill.