Pharmacokinetics of foscarnet and distribution to cerebrospinal fluid after intravenous infusion in patients with human immunodeficiency virus infection.

To investigate the pharmacokinetics and effects of intravenous foscarnet, 13 relatively healthy male patients with human immunodeficiency virus infection and a mean CD4+ lymphocyte value of 0.45 x 10(-9) cells per liter were given a continuous intravenous infusion of foscarnet (0.14 to 0.19 mg/kg per min) for 8 to 21 days. Blood and urine samples were taken during and after drug administration to monitor foscarnet concentrations. Lumbar puncture was performed during the infusion in five patients. The concentrations in plasma showed large variations both within and between patients. The disposition of foscarnet could be explained by a triexponential equation (t1/2 lambda 1, 0.40 to 2.52 h; t1/2 lambda 2, 3.20 to 16.7 h; t1/2 lambda 3, 36 to 196 h). Renal clearance accounted for most of the plasma clearance, the difference probably reflecting the passage of foscarnet into bone. Up to 20% of the cumulative dose may have been deposited in bone 7 days postinfusion. Foscarnet was distributed to the cerebrospinal fluid in a concentration varying from 13 to 68% of the simultaneous concentration in plasma. Polyuria and polydipsia were recorded in all patients. There appears to be an association between the degree of malaise, including symptoms such as nausea, vomiting, fatigue, and headache, and concentrations in plasma above 350 mumol/liter.

Pharmacokinetics and absorption of foscarnet after intravenous and oral administration to patients with human immunodeficiency virus.

Six patients with human immunodeficiency virus were given foscarnet in oral solution, 4000 mg every 6 hours for 3 days, followed by a washout period for 2 days and continuous intravenous infusion of 16,000 mg/24 hr over 72 hours. After oral foscarnet, plasma concentrations were less than 33 mumol/L in four patients; two had occasional concentrations of 35 to 50 mumol/L. The extent of absorption varied between 12% and 22%. During intravenous infusion, plasma concentrations ranged between 75 and 265 mumol/L. The disposition of foscarnet was triphasic, with mean half-lives of 0.45, 3.3, and 18 hours. Excretion data suggested elimination was by tubular secretion and glomerular filtration. Renal clearance was 176 ml/min 1.73 m2. The apparent nonrenal clearance, 40 ml/min 1.73 m2, probably reflects sequestration of foscarnet into bone. Ten percent to 28% of the cumulative dose may have been deposited in bone 2 days after infusion. A slight increase in serum calcium levels and changes in serum phosphate values may reflect the uptake of foscarnet in bone. Five patients had diarrhea (oral) and two had thrombophlebitis (intravenous).