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. Conclusion: Our data suggest comparable pharmacokinetics of foscarnet after intermittent administration BID or TID during a 3-week induction period. Received: 22 January 1996 / Accepted in revised form: 6 November 1996