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© 1992 Oxford University Press

research-article

Hypocalcemia Induced by Foscarnet (Foscavir) Infusion in Dogs

ÂKE; RYRFELDT*, THOMAS NORDGREN{dagger} and JAN LUNDSTRÖM{dagger}

*Laboratory of Safety Assessment, Astra AB S-151 85 Södertälje, Sweden {dagger}Astra Research Centre AB S-151 85 Södertälje, Sweden

Received December 18, 1990; accepted July 19, 1991

Hypocalcemia Induced by Foscarnet (Foscavir) Infusion in Dogs. RYRFELDT, Â., NORDGREN, T., AND LUNDSTRÖM, J. (1992). Fundam. Appl. Toxicol. 18, 126–130.

Foscarnet (Foscavir) is an antiviral drug for intravenous (iv) treatment of cytomegalovirus (CMV) retinitis in immunocompromised patients. The drug forms complexes with divalent metal ions such as Ca2+ and serum calcium levels may be affected during its iv infusion. In this study, the effect on calcium homeostasis was investigated during daily 8-hr infusions of foscarnet in dogs. After priming infusions of 40 or 80 mg/kg administered during 0.5 hr, maintenance infusion rates were 46 or 91 mg/kg/hr (total daily doses of 410 or 810 mg/kg). At the low infusion rate, foscarnet was administered for 5 consecutive days. The mean plateau serum concentration was 0.56 mmol/liter and the main clinical sign was vomiting. Total serum calcium was reduced from about 2.5 to 2.0 mmol/liter and ionized calcium from 1.3 to 0.9 mmol/liter. Parathyroid hormone (PTH) levels in serum were elevated three to six times while calcitriol (1,25- (OH)2D3) levels were unaffected. At the high infusion rate, treatment was discontinued after 1–2 days of dosing due to pronounced adverse clinical signs such as extensive vomitings, apathy, ataxia, and muscle spasms. The mean serum plateau concentration of foscarnet at this dose level was 1.2 mmol/liter. Total serum calcium was reduced from 2.5 to 1.6 mmol/liter and ionized calcium from 1.3 to 0.7 mmol/liter. PTH as well as 1,25-(OH)2D3 levels in serum were elevated. Total and ionized calcium levels were normalized within 16 hr after stopping drug treatment. The results showed that foscarnet infusion affects calcium homeostasis and that calcium monitoring might be considered in the clinical use of the drug.


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