Skip to main content
NCBI home page
Antimicrobial Agents and Chemotherapy logoLink to Antimicrobial Agents and Chemotherapy
. 1996 Sep;40(9):2087–2093. doi: 10.1128/aac.40.9.2087

Single-dose and steady-state pharmacokinetics of hypericin and pseudohypericin.

R Kerb 1, J Brockmöller 1, B Staffeldt 1, M Ploch 1, I Roots 1
PMCID: PMC163478  PMID: 8878586

Abstract

Single-dose and steady-state pharmacokinetics of antivirally acting hypericin (H) and pseudohypericin (PH) were studied in 13 healthy volunteers by administration of St. John's Wort extract LI 160, a plantal antidepressant. Oral administration of 250, 750, and 1,500 micrograms of H and 526, 1,578, and 3,156 micrograms of PH resulted in median peak levels in plasma (Cmax) of 1.3, 7.2, and 16.6 micrograms/liter for H and 3.4, 12.1, and 29.7 micrograms/liter for PH, respectively. The Cmax and the area under the curve values for the lowest dose were disproportionally lower than those for the higher doses. A lag time of 1.9 h for H was remarkably longer than the 0.4-h lag time for PH. Median half-lives for absorption, distribution, and elimination were 0.6, 6.0, and 43.1 h after 750 micrograms of H and 1.3, 1.4, and 24.8 h after 1,578 micrograms of PH, respectively. Fourteen-day treatment with 250 micrograms of H and 526 micrograms of PH three times a day resulted in median steady-state trough levels of 7.9 micrograms/liter for H and 4.8 micrograms/liter for PH after 7 and 4 days, respectively; the corresponding Cssmax levels were 8.8 and 8.5 micrograms/liter, respectively. Kinetic parameters after intravenous administration of Hypericum extract (115 and 38 micrograms for H and PH, respectively) in two subjects corresponded to those estimated after an oral dosage. Both H and PH were initially distributed into a central volume of 4.2 and 5.0 liter, respectively. The mean distribution volumes at steady state were 19.7 liters for H and 39.3 liters for PH, and the mean total clearance rates were 9.2 ml/min for H and 43.3 ml/min for PH. The systemic availability of H and PH from LI 160 was roughly estimated to be 14 and 21%, respectively. Treatment with Hypericum extract, even in high doses, was well tolerated.

Full Text

The Full Text of this article is available as a PDF (293.9 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Andersen D. O., Weber N. D., Wood S. G., Hughes B. G., Murray B. K., North J. A. In vitro virucidal activity of selected anthraquinones and anthraquinone derivatives. Antiviral Res. 1991 Sep;16(2):185–196. doi: 10.1016/0166-3542(91)90024-l. [DOI] [PubMed] [Google Scholar]
  2. Araya O. S., Ford E. J. An investigation of the type of photosensitization caused by the ingestion of St John's Wort (Hypericum perforatum) by calves. J Comp Pathol. 1981 Jan;91(1):135–141. doi: 10.1016/0021-9975(81)90053-0. [DOI] [PubMed] [Google Scholar]
  3. Barnard D. L., Huffman J. H., Morris J. L., Wood S. G., Hughes B. G., Sidwell R. W. Evaluation of the antiviral activity of anthraquinones, anthrones and anthraquinone derivatives against human cytomegalovirus. Antiviral Res. 1992 Jan;17(1):63–77. doi: 10.1016/0166-3542(92)90091-i. [DOI] [PubMed] [Google Scholar]
  4. Carpenter S., Fehr M. J., Kraus G. A., Petrich J. W. Chemiluminescent activation of the antiviral activity of hypericin: a molecular flashlight. Proc Natl Acad Sci U S A. 1994 Dec 6;91(25):12273–12277. doi: 10.1073/pnas.91.25.12273. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Connolly K. J., Hammer S. M. Antiretroviral therapy: strategies beyond single-agent reverse transcriptase inhibition. Antimicrob Agents Chemother. 1992 Mar;36(3):509–520. doi: 10.1128/aac.36.3.509. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Degar S., Prince A. M., Pascual D., Lavie G., Levin B., Mazur Y., Lavie D., Ehrlich L. S., Carter C., Meruelo D. Inactivation of the human immunodeficiency virus by hypericin: evidence for photochemical alterations of p24 and a block in uncoating. AIDS Res Hum Retroviruses. 1992 Nov;8(11):1929–1936. doi: 10.1089/aid.1992.8.1929. [DOI] [PubMed] [Google Scholar]
  7. Diwu Z. Novel therapeutic and diagnostic applications of hypocrellins and hypericins. Photochem Photobiol. 1995 Jun;61(6):529–539. doi: 10.1111/j.1751-1097.1995.tb09903.x. [DOI] [PubMed] [Google Scholar]
  8. Hudson J. B., Harris L., Towers G. H. The importance of light in the anti-HIV effect of hypericin. Antiviral Res. 1993 Feb;20(2):173–178. doi: 10.1016/0166-3542(93)90006-5. [DOI] [PubMed] [Google Scholar]
  9. Lavie G., Mazur Y., Lavie D., Prince A. M., Pascual D., Liebes L., Levin B., Meruelo D. Hypericin as an inactivator of infectious viruses in blood components. Transfusion. 1995 May;35(5):392–400. doi: 10.1046/j.1537-2995.1995.35595259149.x. [DOI] [PubMed] [Google Scholar]
  10. Lavie G., Valentine F., Levin B., Mazur Y., Gallo G., Lavie D., Weiner D., Meruelo D. Studies of the mechanisms of action of the antiretroviral agents hypericin and pseudohypericin. Proc Natl Acad Sci U S A. 1989 Aug;86(15):5963–5967. doi: 10.1073/pnas.86.15.5963. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Lenard J., Rabson A., Vanderoef R. Photodynamic inactivation of infectivity of human immunodeficiency virus and other enveloped viruses using hypericin and rose bengal: inhibition of fusion and syncytia formation. Proc Natl Acad Sci U S A. 1993 Jan 1;90(1):158–162. doi: 10.1073/pnas.90.1.158. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Liebes L., Mazur Y., Freeman D., Lavie D., Lavie G., Kudler N., Mendoza S., Levin B., Hochster H., Meruelo D. A method for the quantitation of hypericin, an antiviral agent, in biological fluids by high-performance liquid chromatography. Anal Biochem. 1991 May 15;195(1):77–85. doi: 10.1016/0003-2697(91)90298-8. [DOI] [PubMed] [Google Scholar]
  13. Meruelo D., Lavie G., Lavie D. Therapeutic agents with dramatic antiretroviral activity and little toxicity at effective doses: aromatic polycyclic diones hypericin and pseudohypericin. Proc Natl Acad Sci U S A. 1988 Jul;85(14):5230–5234. doi: 10.1073/pnas.85.14.5230. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Mueller E. A., Kovarik J. M., van Bree J. B., Lison A. E., Kutz K. Pharmacokinetics and tolerability of a microemulsion formulation of cyclosporine in renal allograft recipients--a concentration-controlled comparison with the commercial formulation. Transplantation. 1994 Apr 27;57(8):1178–1182. doi: 10.1097/00007890-199404270-00007. [DOI] [PubMed] [Google Scholar]
  15. Senthil V., Longworth J. W., Ghiron C. A., Grossweiner L. I. Photosensitization of aqueous model systems by hypericin. Biochim Biophys Acta. 1992 Jan 23;1115(3):192–200. doi: 10.1016/0304-4165(92)90053-w. [DOI] [PubMed] [Google Scholar]
  16. Venning G. R., Scott G. M. New drug treatments for HIV infection and AIDS. A review following the Seventh International Conference on AIDS, Florence 16-21 June 1991. Br J Clin Pharmacol. 1992 Mar;33(3):349–356. doi: 10.1111/j.1365-2125.1992.tb04051.x. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Antimicrobial Agents and Chemotherapy are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES