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

• Published in: Acta pharmacologica Sinica Vol. 32; no. 12; pp. 1549 - 1554
• Main Authors: Sun, Pei-hong, Zhao, Xia, Zhou, Ying, Liang, Yan, Zhang, Hui-lin, Cui, Yi-min, Tao, Ji-ning
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.12.2011; Nature Publishing Group
• Subjects: Biomedical and Life Sciences; Biomedicine; Chromatography, High Pressure Liquid; Female; Hematoporphyrins - administration & dosage; Hematoporphyrins - adverse effects; Hematoporphyrins - pharmacokinetics; Humans; Immunology; Infusions, Intravenous; Internal Medicine; Male; Medical Microbiology; Original; original-article; Pharmacology/Toxicology; Reference Values; Vaccine; 健康; 公差; 志愿者; 注射剂量; 荧光检测法; 药代动力学; 谷丙转氨酶; 静脉滴注; photosensitive drug; hematoporphyrin monomethyl ether; safety; healthy volunteers; pharmacokinetics; hemoporfin; tolerance; port-wine stain
• ISSN: 1671-4083; 1745-7254; 1745-7254
• DOI: 10.1038/aps.2011.132

Aim： 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 Results： Mild and transient adverse events occurred in the trial （n=10）, but none were serious, and no subjects were withdrawn from the trial.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 ha~f-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. Cmax 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%. Conclusion： 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.