A preliminary pharmacokinetic study of intravenous Photofrin in patients.

Photofrin is a light-activated compound used for photodynamic therapy (PDT) of malignant tumors. Although PDT with this drug has been approved for clinical use in the United States, Canada, Japan, and the Netherlands there are few published reports on the biodistribution of Photofrin in humans. In this study we report measurable amounts of Photofrin in human serum up to approximately 1 year following injection of two different Photofrin doses. Concentration-time data were collected from 3, 12, 19, and 10 patients after 0.75, 0.875, 1, and 2 mg Photofrin/kg body weight. Patients who received 2 mg Photofrin/kg were scheduled to undergo intraoperative PDT for the treatment of mesothelioma or carcinoma of the lung. Patients receiving 0.75, 0.875, or 1 mg Photofrin/kg were treated for basal cell carcinoma; 1 mg Photofrin/kg is now a standard dose for PDT of cutaneous malignancies at this institute. For the 1 mg Photofrin/kg dose, a triexponential 3-compartment pharmacokinetic model was fitted to 30 data points pooled from the 19 patients, as if we had one "superpatient." The alpha, beta, and gamma halflives were approximately 16 h, 7.53 days, and 155.56 days, respectively. The mean (+/- SEM) serum concentrations 48 after injection (when most tumors are exposed to drug-activating light) of 0.875, 1, or 2 mg Photofrin/kg were 2.70 +/- 0.47, 4.00 +/- 0.66, and 3.47 +/- 0.97 micrograms Photofrin/ml, respectively. No porphyrin fluorescence could be detected in serum collected from patients 560 to 1335 days after Photofrin injection.