Ocular iontophoretic supplementation of intravenous foscarnet therapy.
OBJECTIVE
Reactivation of cytomegalovirus retinopathy during intravenous antiviral therapy is usually treated with higher doses of drug. We sought to determine whether ocular iontophoresis increases the intravitreal foscarnet concentration attained by intravenous injection.


METHODS
We injected foscarnet (120 mg/kg or 180 mg/kg) intravenously into 24 rabbits and determined the time of maximal concentrations in serum and vitreous humor. We injected the same doses into 24 additional rabbits and administered ocular foscarnet iontophoresis one hour later. Vitreous humor concentrations were assayed at one, four, eight, 24, 60, and 120 hours after iontophoresis and compared with those from injection alone.


RESULTS
Maximum serum and vitreous humor concentrations were achieved one hour after each intravenous dose. Maximum vitreous humor concentrations were achieved four hours after 120 mg/kg intravenous doses plus iontophoresis and eight hours after 180-mg/kg intravenous doses plus iontophoresis. Vitreous humor levels were significantly higher in eyes receiving intravenous foscarnet (120 mg/kg, P < .0001; 180 mg/kg, P < .0001) plus ocular Foscarnet iontophoresis than in those receiving intravenous foscarnet alone. Vitreous humor foscarnet levels in eyes receiving 120 mg/kg intravenously did not differ significantly from those in the group receiving 180 mg/kg intravenously (P < .1). The intravenous dose did not significantly affect vitreous humor levels after iontophoresis (P < .1). Vitreous concentrations fell below therapeutic levels (25 microM) in all eyes 60 hours after intravenous foscarnet and ocular foscarnet iontophoresis.


CONCLUSIONS
Ocular iontophoresis significantly increased intravitreous foscarnet concentrations above those attained by intravenous injection alone and may be an effective alternative to increasing the intravenous drug dose in patients with reactivated cytomegalovirus retinopathy.
Yoshizumi
M O
MO
Department of Ophthalmology, Jules Stein Eye Institute, University of California, Los Angeles 90095-7000, USA.
Roca
J A
JA
Lee
D A
DA
Lee
G
G
Gomez
I
I
D000818:Animals; D000998:Antiviral Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D001682:Biological Availability; D002851:Chromatography, High Pressure Liquid; D017726:Cytomegalovirus Retinitis / Q000188:drug therapy; D017245:Foscarnet / Q000008:administration & dosage* / Q000493:pharmacokinetics; D006207:Half-Life; D007275:Injections, Intravenous; D007478:Iontophoresis; D011817:Rabbits; D014822:Vitreous Body / Q000378:metabolism
D000998:Antiviral Agents; D017245:Foscarnet