Skip to main content
Journal cover image

Potential for a novel manganese porphyrin compound as adjuvant canine lymphoma therapy.

Publication ,  Journal Article
Boss, MK; Dewhirst, MW; Sampaio, RS; Bennett, A; Tovmasyan, A; Berman, KG; Beaven, AW; Rizzieri, DA; Batinic-Haberle, I; Hauck, ML; Spasojevic, I
Published in: Cancer Chemother Pharmacol
August 2017

PURPOSE: Manganese porphyrins are redox-active drugs and superoxide dismutase mimics, which have been shown to chemosensitize lymphoma, a cancer which frequently occurs in dogs. This study aimed to identify critical information regarding the pharmacokinetics and toxicity of Mn(III) meso-tetrakis (N-n-butoxyetylpyridium-2-yl) porphyrin, (MnTnBuOE-2-PyP5+, MnBuOE) in dogs as a prelude to a clinical trial in canine lymphoma patients. METHODS: A single-dose pharmacokinetic (PK) study in normal dogs was performed to determine the plasma half-life (t 1/2) of MnBuOE. A dose reduction study was performed to establish the maximum tolerated dose (MTD) of MnBuOE. The safety and PK of a multi-dosing protocol was assessed. RESULTS: Peak plasma drug concentration occurred 30 min post-injection. The t 1/2 was defined as 7 h. MnBuOE induced an anaphylactic reaction and prolonged tachycardia. The MTD was defined as 0.25 mg/kg. The dogs were given MTD 3×/week for 2-3 weeks. The highest recorded tissue drug levels were in the lymph nodes (4-6 μM), followed by kidney and liver (2.5, 2.0 uM, respectively). CONCLUSIONS: We obtained critical information regarding the PK and toxicity of MnBuOE in dogs. The acute drug reaction and tachycardia post-injection have not been described in other species and may be specific to canines. The high tissue drug levels in lymph nodes have not been previously reported. MnBuOE accumulation in lymph nodes has important implications for the utility of adjuvant MnBuOE to treat lymphoma. With MnBuOE lymph node accumulation, reduction in the dose and/or administration frequency could be possible, leading to reduced toxicity.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

Cancer Chemother Pharmacol

DOI

EISSN

1432-0843

Publication Date

August 2017

Volume

80

Issue

2

Start / End Page

421 / 431

Location

Germany

Related Subject Headings

  • Tissue Distribution
  • Tachycardia
  • Species Specificity
  • Oncology & Carcinogenesis
  • Metalloporphyrins
  • Maximum Tolerated Dose
  • Male
  • Lymphoma
  • Lymph Nodes
  • Liver
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Boss, M. K., Dewhirst, M. W., Sampaio, R. S., Bennett, A., Tovmasyan, A., Berman, K. G., … Spasojevic, I. (2017). Potential for a novel manganese porphyrin compound as adjuvant canine lymphoma therapy. Cancer Chemother Pharmacol, 80(2), 421–431. https://doi.org/10.1007/s00280-017-3372-z
Boss, M. K., M. W. Dewhirst, R. S. Sampaio, A. Bennett, A. Tovmasyan, K. G. Berman, A. W. Beaven, et al. “Potential for a novel manganese porphyrin compound as adjuvant canine lymphoma therapy.Cancer Chemother Pharmacol 80, no. 2 (August 2017): 421–31. https://doi.org/10.1007/s00280-017-3372-z.
Boss MK, Dewhirst MW, Sampaio RS, Bennett A, Tovmasyan A, Berman KG, et al. Potential for a novel manganese porphyrin compound as adjuvant canine lymphoma therapy. Cancer Chemother Pharmacol. 2017 Aug;80(2):421–31.
Boss, M. K., et al. “Potential for a novel manganese porphyrin compound as adjuvant canine lymphoma therapy.Cancer Chemother Pharmacol, vol. 80, no. 2, Aug. 2017, pp. 421–31. Pubmed, doi:10.1007/s00280-017-3372-z.
Boss MK, Dewhirst MW, Sampaio RS, Bennett A, Tovmasyan A, Berman KG, Beaven AW, Rizzieri DA, Batinic-Haberle I, Hauck ML, Spasojevic I. Potential for a novel manganese porphyrin compound as adjuvant canine lymphoma therapy. Cancer Chemother Pharmacol. 2017 Aug;80(2):421–431.
Journal cover image

Published In

Cancer Chemother Pharmacol

DOI

EISSN

1432-0843

Publication Date

August 2017

Volume

80

Issue

2

Start / End Page

421 / 431

Location

Germany

Related Subject Headings

  • Tissue Distribution
  • Tachycardia
  • Species Specificity
  • Oncology & Carcinogenesis
  • Metalloporphyrins
  • Maximum Tolerated Dose
  • Male
  • Lymphoma
  • Lymph Nodes
  • Liver