Hypericin, a polycyclic aromatic dianthroquinone, is a natural pigment deri
ved from the plant Hypericum perforatum (St John's Wort). The compound has
been synthesized and shown to inhibit the growth of malignant glioma cell l
ines in vitro via inhibition of protein kinase C. Oral hypericin has entere
d clinical trials in adults with recurrent malignant glioma. Purpose: The p
resent study was performed to characterize the plasma pharmacokinetics (PK)
and cerebrospinal fluid (CSF) penetration of hypericin in nonhuman primate
s. Methods: Hypericin was administered as an intravenous bolus dose of 2 mg
/kg (n = 3) or 5 mg/kg (n = 1). Plasma and CSF (ventricular or lumbar) were
sampled Frier to administration and at frequent intervals for up to 50 h a
fter administration of the drug. Hypericin concentrations in plasma and CSI
; were determined using a specific reverse-phase HPLC assay. Results: Mean
peak plasma concentration of hypericin following the 2 mg/kg dose was 142 /- 45 muM. Elimination of hypericin from plasma was biexponential, with an
average alpha half-life of 2.8 +/- 0.3 h and average terminal half-life of
26 +/- 14 h. Conclusions: The 2 mg/kg dose in the nonhuman primate was suff
icient to maintain plasma concentrations above 10 muM (the in vitro concent
ration required for growth inhibition of human glioma cell lines) for up to
12 h. No hypericin was detected in the CSF of any animal (lower limit of d
etection 0.1 muM); the CSF penetration is therefore less than 1%. A severe
dose-limiting photosensitivity skin rash was seen at the 5 mg/kg dose level
.