Lack of effect of sex and disease state on the pharmacokinetics of porfimer sodium.

Background: Porfimer sodium is an agent used for photodynamic therapy (PDT) of cancer and other pre-malignant conditions such as high grade dysplasia in Barrett's oesophagus. Since it is activated by non-thermal red light after a 2-day time interval to allow distribution in the target tissues, its pharmacokinetic properties are relevant to the timing of light treatment and to the period of protection against photosensitivity reactions. With the recent availability of a reliable assay overcoming the limitations of previous assays, two definitive pharmacokinetic studies were undertaken.

Objective: To determine if sex or a target disease state (cancer) have an effect on porfimer sodium pharmacokinetic parameters.

Methods: Twenty-four healthy volunteers (12 men and 12 women) and five male patients with oesophageal cancer undergoing palliative PDT for their obstructive lesions were enrolled. All received an intravenous injection of porfimer sodium (Photofrin) 2 mg/kg over 3-5 minutes and underwent serial blood samplings over 35 days postdose. Porfimer sodium was quantified in serum by a validated spectrofluorometry assay and low-level pre-existing interference was subtracted from postdose concentrations.

Results: The two sexes had comparable maximum serum concentrations with a ratio of 0.95. Women tended to have higher areas under the serum concentration-time curve from time zero to the last sampling time, and from time zero to infinity than men, but the difference did not reach significance (ratios of means of 1.18 and 1.20, respectively). Elimination parameters also showed no sex-related differences with a mean distribution half-life of 9.5 hours, clearance of 0.88 mL/h/kg and a terminal elimination half-life of 415 hours (17.3 days). The sexes only differed significantly for the time to reach maximum serum concentration (means of 1.54 and 0.165 hours, for women and men, respectively; p = 0.0239). This is probably because of the sparse sampling schedule and the plateau behaviour of the initial concentrations. The pharmacokinetic parameters in cancer patients were generally comparable to healthy volunteers. However, the mean terminal elimination half-life was 30% shorter (283 hours or 11.8 days) in cancer patients.

Conclusion: Sex does not have an effect on porfimer sodium pharmacokinetics. The presence of advanced oesophageal cancer does not seem to have any influence either. These findings confirm that there is no need for sex-specific label recommendations. Also, the elimination phase of porfimer sodium starting progressively from 24 hours postdose supports the recommended time interval for laser light application, the window for PDT debridement and the skin protection period of at least 30 days.