Pharmacokinetics of pyropheophorbide-a-hexyl ether in the dog.
OBJECTIVE
Pyropheophorbide-a-hexyl ether (HPPH) is a new compound being investigated for use as a photosensitizer for photodynamic therapy; however, the pharmacokinetics are not known for any of the target species likely to be treated with this drug. The objective of this study was to determine the pharmacokinetic parameters of this drug prior to institution of a clinical trial in canine patients with various cancers.


METHODS
HPPH (0.3mg/kg i.v.) was administered to 12 dogs and blood samples were drawn at intervals for 24 hours and plasma HPPH concentrations were determined. Pharmacokinetic parameters were calculated for each dog.


RESULTS
No evidence of toxicity was noted in any dog. The mean half-life was calculated to be 26.98 +/- 2.35 hrs. The mean clearance was 5.061 +/- 0.214 ml/hr/kg. The mean volume of distribution of the central compartment was 0.069 +/- 0.003 L/kg, and the mean steady state volume of distribution was 4.47 +/- 0.25 L/kg.


CONCLUSIONS
The conclusion is that 0.3 mg/kg HPPH injected intravenously resulted in measurable plasma levels for 24 hrs, and resulted in no detectable adverse reactions.
Payne
J T
JT
Department of Veterinary Medicine, University of Missouri-Columbia 65211, USA.
McCaw
D L
DL
Casteel
S W
SW
Frazier
D
D
Rogers
K
K
Tompson
R V
RV
D000818:Animals; D002734:Chlorophyll / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D004285:Dogs; D005260:Female; D006207:Half-Life; D008297:Male; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use
D017319:Photosensitizing Agents; D002734:Chlorophyll; C083998:2-(1-hexyloxyethyl)-2-devinyl pyropheophorbide-a