Pharmacology of mitoxantrone

mode of action and pharmacokinetics

David S Alberts, Yei Mei Peng, G. Timothy Bowden, William S. Dalton, Cindy Mackel

Research output: Contribution to journalArticle

74 Citations (Scopus)

Abstract

Although a number of investigators have established that mitoxantrone (Novantrone®; dihydroxyanthracenedione) inhibits RNA and DNA synthesis and intercalates with DNA in vitro, its exact mechanism of action is unclear. Mitoxantrone is structurally related to a series of substituted anthraquinones and has features known to be essential for DNA intercalation; however, we have determined recently that mitoxantrone binds DNA in intact L1210 leukemia cells by a non-intercalative, electrostatic interaction and induces both protein associated and non-protein associated DNA strand scissions. The difference between mitoxantrone and doxorubicin with respect to their interactions with DNA could account for their relative lack of cross-resistance in the treatment of lymphoma and acute leukemia. Distribution and half-life data provide a pharmacological rationale for the use of mitoxantrone on an intermittent dosing schedule. Considerable evidence exists to suggest that mitoxantrone undergoes extensive metabolism, probably in the liver. Preliminary data show that abnormal liver function leads to decreased rates of total body mitoxantrone clearance, suggesting a possible need for dose reduction in patients with severe liver dysfunction. The most important route of mitoxantrone elimination appears to be fecal. Because of the relatively low urinary excretion it is unlikely that the standard drug dose must be reduced in the presence of compromised renal function.

Original languageEnglish (US)
Pages (from-to)101-107
Number of pages7
JournalInvestigational New Drugs
Volume3
Issue number2
DOIs
StatePublished - Jun 1985

Fingerprint

Mitoxantrone
Pharmacokinetics
Pharmacology
DNA
Metabolic Clearance Rate
Leukemia L1210
Anthraquinones
Liver
Static Electricity
Doxorubicin
Half-Life
Liver Diseases
Lymphoma
Appointments and Schedules
Leukemia
Research Personnel
RNA
Kidney

Keywords

  • elimination
  • mitoxantrone
  • mode of action
  • pharmacokinetics

ASJC Scopus subject areas

  • Pharmacology
  • Molecular Medicine

Cite this

Pharmacology of mitoxantrone : mode of action and pharmacokinetics. / Alberts, David S; Peng, Yei Mei; Bowden, G. Timothy; Dalton, William S.; Mackel, Cindy.

In: Investigational New Drugs, Vol. 3, No. 2, 06.1985, p. 101-107.

Research output: Contribution to journalArticle

Alberts, David S ; Peng, Yei Mei ; Bowden, G. Timothy ; Dalton, William S. ; Mackel, Cindy. / Pharmacology of mitoxantrone : mode of action and pharmacokinetics. In: Investigational New Drugs. 1985 ; Vol. 3, No. 2. pp. 101-107.
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