Comparative pharmacokinetics of the photosensitizer tin-etiopurpurin in dogs and rats.
Photodynamic therapy is a promising new treatment for local eradication of cancer. Little work has been done to define the pharmacokinetics of photodynamic drugs or the variability in drug disposition that may occur between different species and pathophysiological states of tissues. Pharmacokinetic studies of tin-etiopurpurin (SnET2), a lipophilic photosensitizer, were conducted on six Beagle dogs and six Sprague-Dawley rats. Blood was collected up to 24 h following drug administration for measurement of tin-etiopurpurin concentration. Dogs and rats were euthanatized 24 h post-administration and tissues were collected for drug analyses. The plasma drug concentrations were best described by a 2-compartment model (Ct = Ae-alpha t + Be-beta t). Median distribution and elimination half-lives were 0.24 and 0.34 h and 10.21 and 5.25 h for dogs and rats, respectively. The apparent volumes of distribution were 4.26 +/- 1.75 L/kg for dogs and 1.84 +/- 0.36 L/kg for rats. Systemic clearance was 7.56 +/- 2.45 ml/kg/min and 6.63 +/- 0.91 ml/kg/min for dogs and rats, respectively. Drug was detected in all tissues analyzed 24 h after drug administration. Drug was detected only sporadically in skin and muscle and was generally below the limit of detection of the assay. Where comparisons could be made, concentrations of SnET2 were significantly greater in all tissues except jejunum of rats compared to dogs 24 h after drug administration.
Frazier
D L
DL
Department of Environmental Practice and Urban Practice, University of Tennessee College of Veterinary Medicine, Knoxville 37901.
Barnhill
M A
MA
Vodinh
T
T
Legendre
A M
AM
Overholt
B F
BF
D000818:Animals; D004285:Dogs / Q000378:metabolism*; D006207:Half-Life; D008297:Male; D008657:Metabolic Clearance Rate; D011166:Porphyrins / Q000097:blood / Q000493:pharmacokinetics; D011838:Radiation-Sensitizing Agents / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley / Q000378:metabolism*; D013045:Species Specificity; D014018:Tissue Distribution
D011166:Porphyrins; D011838:Radiation-Sensitizing Agents; C063166:tin etiopurpurin