LIPOSOMAL ENCAPSULATION OF FOSCARNET PROTECTS AGAINST HYPOCALCEMIA INDUCED BY FREE FOSCARNET

Hypocalcemia and an increase in creatinine level are the most importan t serious effects associated with foscarnet (PFA) therapy. In an anima l model, we have explored the potential protective role of liposome-en capsulated foscarnet (LE-PFA) on these metabolic abnormalities. PFA ad ministered as one bolus injection (0.5 or 1.0 g/kg) caused significant rapid decreases (similar to 20%) in the levels of calcium and phospho rus in serum within a few minutes and up to 30 min after injection. LE -PFA did not induce any of these changes, while peak levels in serum a nd the half-life of this formulation were much higher than those of th e free drug, PFA administered for 2 weeks (340 or 500 mg/kg/day) resul ted in no changes in creatinine or blood urea nitrogen levels in serum at the low-dosage level, but at the higher-dosage level, the creatini ne level in serum increased by day 5 posttreatment. Furthermore, there was no increase in the creatinine or blood urea nitrogen level after 2 weeks of treatment with LE-PFA at a dosage of 35 mg/kg/day. When the pharmacokinetics of both free PFA and LE-PFA were compared, the plasm a half-life of the encapsulated drug was similar to four times longer than that of the free drug. In addition, the systemic clearance of LE- PFA was similar to one-fifth of that of the free drug. In conclusion, free PFA causes hypocalcemia and hypophosphatemia and increases the cr eatinine level in serum, whereas the LF form of this drug seems to pro tect against the abnormal changes in calcium and phosphorus levels cau sed by the free drug. By preventing hypocalcemia and increasing its ha lf-life, LE-PFA can be used at lower doses and at longer intervals, Cl inical investigations of these formulations may be worthwhile.