Development of a parenteral formulation for the anti-tumour agent acronycine

Robert T Dorr, J. D. Liddil

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

Acronycine is an anti-tumour alkaloid isolated from the bark of Acronychia baueri. It is active in a number of murine tumours and in multiple myeloma in humans. A serious limitation to broad clinical testing of acronycine is the lack of aqueous solubility due, in part, to its lipophilicity (log P value of 2.6). Acronycine powder was dissolved in the same co-solvent system used for etoposide (VP-16). This VP-16 diluent (VPD) consists of PEG 300, ethanol and polysorbate 80. Resulting acronycine solutions could then be further diluted with 5% dextrose, 0.9% sodium chloride or RPMI 1640 culture medium for 4-72 hours at temperatures from 0°C to 37°C. Acronycine in VPD retarded calf thymus DNA thermal denaturation in a pattern consistent with intercalation or some other non-covalent interaction. When dissolved in 5% DMSO, no such effect on DNA was produced. The aqueous formulation of acronycine in VPD was active against L-1210 leukaemia in vitro and was tolerated in mice at doses up to 30 mg/kg/day i.p. or 1.4 mg/kg/day i.v. for five consecutive days. Furthermore, an i.p. regimen of 25 mg/kg was active in mice bearing the MOPC-315 plasmacytoma tumour i.p. Since acronycine has shown anti-tumour activity in multi-drug-resistant CHO cells in vitro, and in human multiple myeloma (using a poorly-absorbed capsule formulation), the new availability of a tolerable parenteral solution could support further clinical testing of acronycine at increased dose levels.

Original languageEnglish (US)
Pages (from-to)31-39
Number of pages9
JournalJournal of Drug Development
Volume1
Issue number1
StatePublished - 1988

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Acronine
Etoposide
Neoplasms
Multiple Myeloma
Rutaceae
Nucleic Acid Denaturation
Leukemia L1210
Plasmacytoma
CHO Cells
Polysorbates
Dimethyl Sulfoxide
Alkaloids
Sodium Chloride
Powders
Solubility
Capsules
Culture Media
Ethanol
Hot Temperature

ASJC Scopus subject areas

  • Pharmacology

Cite this

Development of a parenteral formulation for the anti-tumour agent acronycine. / Dorr, Robert T; Liddil, J. D.

In: Journal of Drug Development, Vol. 1, No. 1, 1988, p. 31-39.

Research output: Contribution to journalArticle

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