Tolerance and pharmacokinetics of single-dose intravenous hemoporfin in healthy volunteers.

OBJECTIVE

To investigate the safety, tolerability and pharmacokinetics of intravenous hemoporfin, a novel photosensitive drug for the treatment of port-wine stain (PWS), in healthy Chinese volunteers following single-dose administration.

METHODS

Thirty-six healthy Chinese subjects were enrolled. The subjects were administered hemoporfin (2.5, 5, 7.5 or 10 mg/kg) via single-dose intravenous infusion. Pharmacokinetics of the drug were studied in the groups with doses of 2.5, 5 and 7.5 mg/kg, and tolerability was studied in all the 4 groups. Safety and tolerance were evaluated by monitoring adverse events and laboratory parameters, and pharmacokinetics were assessed by determining hemoporfin content with a validated high-performance liquid chromatography with fluorescence detection (HPLC/FLD) method.

RESULTS

Mild and transient adverse events occurred in the trial (n=10), but none were serious, and no subjects were withdrawn from the trial. The gastrointestinal tract adverse events, such as nausea, stomach upset, abdominal pain and vomiting, were observed in the groups with doses of 7.5 and 10 mg/kg. Increased alanine aminotransferase (ALT) concentration was found in 3 subjects, and increased alkaline phosphatase (ALP) concentration in one subject. The half-life of hemoporfin for doses of 2.5, 5, and 7.5 mg/kg was 1.26 h, 1.31 h, and 1.70 h, respectively. C(max) and AUC increased with dose for intravenous single-dose administration of hemoporfin in the 2.5, 5, and 7.5 mg/kg groups. Urinary excretion of hemoporfin within 12 h was less than 0.2%.

CONCLUSIONS

Hemoporfin is safe and well-tolerated in healthy Chinese volunteers at a single intravenous dose of up to 10 mg/kg. It was rapidly cleared from the blood and had a short half-life, which insures a short light-avoidance period.