|Tolerance and pharmacokinetics of single-dose intravenous hemoporfin in healthy volunteers|
|Sun, Pei-hong1; Zhao, Xia1; Zhou, Ying1; Liang, Yan1; Zhang, Hui-lin1; Cui, Yi-min1; Tao, Ji-ning2|
|关键词||port-wine stain photosensitive drug hemoporfin hematoporphyrin monomethyl ether pharmacokinetics tolerance healthy volunteers safety|
|刊名||ACTA PHARMACOLOGICA SINICA|
|WOS标题词||Science & Technology|
|类目[WOS]||Chemistry, Multidisciplinary ; Pharmacology & Pharmacy|
|研究领域[WOS]||Chemistry ; Pharmacology & Pharmacy|
|关键词[WOS]||PORT-WINE STAIN ; P-GLYCOPROTEIN ; BIRTHMARKS|
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Results: Mild and transient adverse events occurred in the trial (n=10), but none were serious, and no subjects were withdrawn from the trial.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 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%.
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.
|作者单位||1.Peking Univ, Hosp 1, Dept Pharm, Beijing 100034, Peoples R China|
2.Shanghai Fudan Zhangjiang Biopharmaceut Co Ltd, Shanghai 201203, Peoples R China
|Sun, Pei-hong,Zhao, Xia,Zhou, Ying,et al. Tolerance and pharmacokinetics of single-dose intravenous hemoporfin in healthy volunteers[J]. ACTA PHARMACOLOGICA SINICA,2011,32(12):1549-1554.|
|APA||Sun, Pei-hong.,Zhao, Xia.,Zhou, Ying.,Liang, Yan.,Zhang, Hui-lin.,...&Tao, Ji-ning.(2011).Tolerance and pharmacokinetics of single-dose intravenous hemoporfin in healthy volunteers.ACTA PHARMACOLOGICA SINICA,32(12),1549-1554.|
|MLA||Sun, Pei-hong,et al."Tolerance and pharmacokinetics of single-dose intravenous hemoporfin in healthy volunteers".ACTA PHARMACOLOGICA SINICA 32.12(2011):1549-1554.|