Kinetics of gallium nitrate, a new anticancer agent.
Pharmacokinetic studies were conducted in 8 patients with disseminated neoplasms refractory to conventional chemotherapy, who received gallium nitrate at doses of 300 to 600 mg/m2 intravenously in a phase I clinical trial. Gallium concentrations in biological fluids were determined colorimetrically. In patients with normal renal function, gallium showed a biphasic plasma disappearance with an initial half-life (t1/2) of 0.5 to 1.8 hr (mean 1.0) and a terminal t1/2 of 10.5 to 50.4 hr (mean 25.1). Gallium was distributed in total body water and often localized in some body compartment as evidenced by a volume of distribution ranging from 0.25 to 2.53 L/kg (mean 1.19). The total drug clearance from the plasma was 0.13 to 1.00 ml/kg/min (mean 0.65) in patients with normal renal function. Cumulative urinary excretion of gallium was 15% to 72% (mean 35%) of the administered dose in 24 hr (it fell to 23% in 8 days in a patient with acute oliguric renal failure). Gallium kinetics are altered in patients with acute renal dysfunction and in patients who have received multiple doses of gallium or other metal chemotherapy.
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000378:metabolism*; D005260:Female; D005708:Gallium / Q000378:metabolism*; D006207:Half-Life; D006801:Humans; D007674:Kidney Diseases / Q000150:complications / Q000378:metabolism; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D009369:Neoplasms / Q000150:complications / Q000378:metabolism; D009566:Nitrates / Q000378:metabolism
D000970:Antineoplastic Agents; D009566:Nitrates; D005708:Gallium