Foscarnet (
phosphonoformate) is a potent virustatic
drug against herpes-like viruses and is widely used in the
therapy of
cytomegalovirus infections in immunosuppressed patients. To obtain data on its penetration across the blood-brain barrier, we determined concentrations of
foscarnet in cerebrospinal fluid and in plasma specimens from 26 patients with human immunodeficiency virus (stages 2 to 6 by Walter Reed Army Institute of Research classification) after a single infusion of 90 mg of
foscarnet per kg of
body weight and at steady state by electrochemical detection by high-pressure liquid chromatography. Penetration coefficients were correlated with the integrity of the blood-brain barrier. After a single infusion of
foscarnet, levels in plasma ranged from 297 to 1,775 micrograms/ml (990 to 5,920 mumol/liter), with a mean of 766 +/- 400 micrograms/ml. Corresponding levels in cerebrospinal fluid were 57 to 225 micrograms/ml (190 to 750 mumol/liter), with a mean of 131 +/- 52 micrograms/ml. The penetration coefficient was 0.05 to 0.72 (mean, 0.23 +/- 0.16). At steady state, mean
foscarnet levels in plasma were 464 +/- 219 micrograms/ml (1,553 mumol/liter) and mean levels in cerebrospinal fluid were 308 +/- 155 micrograms/ml (1,023 mumol/liter). The penetration coefficient was 0.66 +/- 0.11. Although penetration coefficients were highly variable after a single administration and at steady state, the concentrations of
foscarnet attained in cerebrospinal fluid are sufficient for complete inhibition of cytomegalovirus replication in vitro. In conclusion, we show that
foscarnet seems to be the
drug of choice for the treatment of cytomegalovirus
encephalitis, because it penetrates the blood-brain barrier and is found in the cerebrospinal fluid in virustatic concentrations.
Foscarnet might be considered for additive
therapy for human immunodeficiency virus
encephalitis in combination with
zidovudine or
dideoxyinosine.