Comparison of pharmacokinetics and dynamics of two dosage regimens of foscarnet in AIDS patients with Cytomegalovirus retinitis.
OBJECTIVE
To compare the pharmacokinetics of foscarnet administered as an infusion twice daily (BID) or thrice daily (TID), and to compare the effects on the electrolyte balance, cardiac and renal functions over a 3-week induction treatment of Cytomegalovirus (CMV) retinitis.


METHODS
Pharmacokinetics/dynamics of foscarnet were investigated on treatment days 1, 14 and 21. Twelve AIDS patients with CMV retinitis completed the investigation period. Concentrations of foscarnet and electrolytes were assayed by high-performance liquid chromatography (HPLC) and by an ion-selective analyser, respectively.


RESULTS
The pharmacokinetics of the two regimens were essentially similar. Foscarnet plasma and creatinine clearances were 2.0 and 1.6 ml.min-1.kg-1, respectively, in the BID group at steady state (day 21). In the TID group the corresponding values were 1.8 and 1.7 ml.min-1.kg-1, respectively. In both regimens the elimination half-life of foscarnet was 2-3 h. Ionized calcium concentrations were transiently decreased and strongly inversely correlated to foscarnet plasma concentrations in both regimens with no significant differences between groups. A trend towards prolongation of the QTc interval was seen when data from both treatments were analysed together.


CONCLUSIONS
Our data suggest comparable pharmacokinetics of foscarnet after intermittent administration BID or TID during a 3-week induction period.
Castelli
F
F
Clinic of Infectious and Tropical Diseases, University of Brescia, Italy.
Tomasoni
L
L
Zeroli
C
C
Suter
F
F
Trespi
G
G
Carosi
G
G
Hedman
A
A
D017088:AIDS-Related Opportunistic Infections / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D000293:Adolescent; D000328:Adult; D000998:Antiviral Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use; D002118:Calcium / Q000097:blood; D017726:Cytomegalovirus Retinitis / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D004562:Electrocardiography; D005260:Female; D017245:Foscarnet / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use; D006801:Humans; D007677:Kidney Function Tests; D008297:Male
D000998:Antiviral Agents; D017245:Foscarnet; D002118:Calcium