Pharmacokinetics, safety, and antiviral effects of hypericin, a derivative of St. John's wort plant, in patients with chronic hepatitis C virus infection.
Hypericin is a natural derivative of the common St. Johns wort plant, Hypericum perforatum. It has in vitro activity against several viruses, including bovine diarrhea virus, a pestivirus with structural similarities to hepatitis C virus (HCV). We conducted a phase I dose escalation study to determine the safety and antiviral activity of hypericin in patients with chronic HCV infection. The first 12 patients received an 8-week course of 0.05 mg of hypericin per kg of body weight orally once a day; 7 patients received an 8-week course of 0.10 mg/kg orally once a day. At the end of the 8-week period of treatment, no subject had a change of plasma HCV RNA level of more than 1.0 log(10). Five of 12 subjects receiving the 0.05-mg/kg/day dosing schedule and 6 of 7 subjects receiving the 0.10-mg/kg/day dosing schedule developed phototoxic reactions. No other serious adverse events associated with hypericin use occurred. The pharmacokinetic data revealed a long elimination half-life (mean values of 36.1 and 33.8 h, respectively, for the doses of 0.05 and 0.1 mg/kg) and mean area under the curve determinations of 1.5 and 3.1 microg/ml x hr, respectively. In sum, hypericin given orally in doses of 0.05 and 0.10 mg/kg/d caused considerable phototoxicity and had no detectable anti-HCV activity in patients with chronic HCV infection.
Jacobson
J M
JM
Department of Medicine, Mount Sinai Medical Center, New York, NY 10029, USA. jeffrey.jacobson@mssm.edu
Feinman
L
L
Liebes
L
L
Ostrow
N
N
Koslowski
V
V
Tobia
A
A
Cabana
B E
BE
Lee
D
D
Spritzler
J
J
Prince
A M
AM
D000293:Adolescent; D000328:Adult; D000873:Anthracenes; D000998:Antiviral Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001219:Aspartate Aminotransferases / Q000097:blood; D005260:Female; D005500:Follow-Up Studies; D006207:Half-Life; D016174:Hepacivirus / Q000737:chemistry; D019698:Hepatitis C, Chronic / Q000150:complications / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D008297:Male; D008875:Middle Aged; D010569:Perylene / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D010787:Photosensitivity Disorders / Q000139:chemically induced; D012367:RNA, Viral / Q000032:analysis
D000873:Anthracenes; D000998:Antiviral Agents; D012367:RNA, Viral; D010569:Perylene; C004965:hypericin; D001219:Aspartate Aminotransferases