Plasma pharmacokinetics and tissue biodistribution of boron following administration of a boronated porphyrin in dogs.
This study was undertaken to determine the plasma pharmacokinetics and tissue biodistribution of boron in dogs following the administration of a boronated porphyrin (BOPP) compound, a potential sensitizing agent for binary therapies of cancer. An intravenous dose of 35 mg/kg of BOPP was administered to a total of sixteen dogs and plasma samples obtained at multiple time points for up to 28 days after administration. Groups of four dogs each were studied for 25, 79, 240, and 672 h. At the end of each study period, subjects were sacrificed and tissue samples obtained. Boron concentrations were determined for all tissue and plasma samples, and pharmacokinetic parameters were determined using mixed effects modeling. Plasma boron levels displayed triexponential kinetics with a long terminal half-life and small volume of distribution. Liver, lymph node, adrenal, and kidney tissues accumulated the highest levels of boron, with very low levels associated with most tissues of the head. We conclude that BOPP has pharmacokinetic and tissue distribution properties that suggest that it may be a suitable compound for use as a sensitizing agent in binary therapy of cancer.
Tibbitts
J
J
Department of Pharmaceutical Chemistry, School of Pharmacy, University of California, San Franciscoa 94143, USA.
Sambol
N C
NC
Fike
J R
JR
Bauer
W F
WF
Kahl
S B
SB
D000818:Animals; D001895:Boron / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D016754:Boron Neutron Capture Therapy; D004285:Dogs; D008297:Male; D011166:Porphyrins / Q000008:administration & dosage* / Q000737:chemistry; D014018:Tissue Distribution
D011166:Porphyrins; D001895:Boron