Toxicology of a boronated porphyrin in dogs.
Among the most important characteristics of any therapeutic agent are efficacy and an acceptable toxicity. Prior to human use, toxicity studies are performed in both small and large animal models. Our laboratory has developed a new binary therapy agent, a boronated porphyrin (BOPP), with excellent potential efficacy. The purpose of this study is to examine the toxicology of this compound in dogs. Sixteen dogs were given 35 mg/kg of BOPP intravenously and evaluated for up to 28 days following administration. Clinical and pathologic responses were measured. BOPP was clinically well tolerated with some cases of weight loss, vomiting and mild photosensitivity. Adverse effects were limited primarily to thrombosis at the administration site in several subjects and three cases of mild, possibly transient, liver injury. Clinical pathologic tests found reversible changes in white blood cell counts and platelets, with neither change being clinically significant. The low toxicity associated with BOPP as shown in this study provides valuable evidence supporting the use of BOPP in binary therapy.
Tibbitts
J
J
Department of Biopharmaceutical Sciences, University of California-San Francisco 94143-0446, USA.
Fike
J R
JR
Lamborn
K R
KR
Bollen
A W
AW
Kahl
S B
SB
D000818:Animals; D001896:Boron Compounds / Q000009:adverse effects*; D003905:Deuteroporphyrins / Q000009:adverse effects*; D004285:Dogs; D008297:Male; D017319:Photosensitizing Agents / Q000009:adverse effects*; D000098851:Carboranes
D001896:Boron Compounds; D003905:Deuteroporphyrins; D017319:Photosensitizing Agents; C080251:2,4-(alpha,beta-dihydroxyethyl)deuteroporphyrin IX tetrakiscarborane carboxylate ester; D000098851:Carboranes