A phase Ι study to evaluate the application of photocyanine using pharmacokinetic and pharmacodynamic analysis in...

Photodynamic therapy (PDT) schedules are based on sensitiser dose, light dose, and drug-light interval. The aim of the phase Ι study was to choose optimal dose and drug-light interval for PDT with photocyanine using pharmacokinetics (PK) and pharmacodynamics (PD).

Twenty-eight cancer patients were enrolled. In trial A, 12 patients received one of four ascending doses of photocyanine intravenously 24 h prior to 180-270 J/cm² illumination. 0.2 mg/kg dose was infused to ten patients 12-48 h prior to 120 J/cm² illumination in trial B. In trial C, 0.1 mg/kg dose was infused to six patients 6 or 12 h prior to 180-270 J/cm² illumination. Serum concentrations of photocyanine were measured, and simulations were performed to assess the effect of drug exposure in tissue on responses.

Analysis of photocyanine levels of patients indicated that the two-compartment model best fit the data. Simulations showed that the rates of the drug entering tissues and leaving tissues were equal at 8-12 h after injection. Patients experienced pain which was related to photocyanine serum levels, especially with serum levels above 2500 ng/ml. Fewer non-responders were observed at serum levels higher than 1000 ng/ml for illumination at least 12 h after administration.

It is the first report of human trials of photocyanine, and the results suggested that patients receive 180 J/cm² illumination about 20-30 min at serum concentrations of photocyanine between 1000 and 2500 ng/ml at least 10 h after administration.