Foscarnet and ganciclovir pharmacokinetics during concomitant or alternating maintenance therapy for AIDS-related cytomegalovirus retinitis

Introduction: The use of foscarnet and ganciclovir as a combination treatment for cytomegalovirus retinitis is increasing because of limitations associated with single agent therapy. Methods: The pharmacokinetics of foscarnet and ganciclovir were determined in 13 patients receiving either concomitant therapy (regimen A) or daily alternating therapy (regimen B) for maintenance of cytomegalovirus disease. For regimen A, 60 mg/kg intravenous foscarnet and 3.75 mg/kg ganciclovir were sequentially administered daily; for regimen B, 120 mg/kg foscarnet and 6 mg/kg ganciclovir were administered on alternating days. For both regimens, serial blood sampling for pharmacokinetic analysis was performed for each drug alone (day 1 or 2) and after 2 weeks of combination therapy. Plasma samples for foscarnet and ganciclovir analysis were performed by means of high-performance liquid chromatography. Pharmacokinetic analysis was performed with noncompartmental methods. Results: For regimen A, the plasma clearance (CL) of foscarnet did not change in the presence of ganciclovir,averaging 0.12 ± 0.08 and 0.11 ± 0.02 L/hr/kg on study days 2 and 14, respectively (p = 0.34). The volume of distribution (V(ss)) and mean residence time (MRT) also did not change significantly. CL and MRT of foscarnet did not change for regimen B, although a slight increase in V(ss) was observed before (0.38 ± 0.05 L/kg) and after (0.46 ± 0.07 L/kg) alternating therapy (p = 0.03). Ganciclovir CL did not change for either regimen, with mean values of 0.21 ± 0.10 and 0.25 ± 0.10 L/hr/kg (regimen A, p = 0.17) and 0.32 ± 0.10 and 0.34 ± 0.11 L/hr/kg (regimen B, p = 0.24). MRT and V(ss) were also not significantly different. Conclusion: These plasma data suggest that further dosage adjustments are unneccessary for concomitant or alternating maintenance therapy.