Clinical pharmacokinetics of anti-angiogenic photodynamic therapy with benzoporphyrin derivative monoacid ring-A in dogs having naturally occurring neoplasms.

Abstract

The aim of this study was to examine the pharmacokinetics of clinically applied benzoporphyrin derivative monoacid ring-A (BPD-MA; Verteporfin), a second-generation photosensitizer, during a trial of photodynamic therapy (PDT) in nine dogs having naturally occurring neoplasms. After injecting BPD-MA at 0.5 mg/kg intravenously, its mean half-life (t1/2) was found to be 8.14 +/- 5.34 h, mean clearance (Cl) 35.13 +/- 9.62 ml/(h kg), the mean value of the volume of distribution (Vc) 0.08 +/- 0.01 l/kg and the mean steady state volume of distribution (Vss) 0.38 +/- 0.31 l/kg respectively. With the exception of a transitional increase in serum alkaline phosphatase activity, no other clinical abnormalities were observed. The t1/2 in dogs with naturally occurring tumours was longer than that in humans, but similar to that in rats. The values of Cl and Vss in dogs having naturally occurring neoplasms were lower than those in humans. It is suggested that the pharmacokinetics of BPD-MA in tumour-bearing dogs would be helpful in determining the protocol of a short drug-light interval PDT with BPD-MA that mainly targets the tumour vasculature.