Pharmacokinetics of arsenic trioxide (As₂O₃) in Chinese primary hepatocarcinoma patients.

Arsenic trioxide (As₂O₃) induces growth inhibition and apoptosis in human hepatocarcinoma cell lines, but little is known about its pharmacology with this cancer in vivo. Pharmacokinetics after As₂O₃ injection into patients with a primary hepatocarcinoma (PHC) were therefore investigated.Fourteen patients were enrolled after providing informed consent and given daily intravenous doses of 10 mg for 14 days. Three mL blood samples were collected before and 1 h, 2 h, 3 h, 4 h, 5 h, 6 h, 8 h, 12 h and 24 h after the drug infusion on days 1 and 14, as well as once every other day from day 2, for measurement of plasma concentrations using an atom fluorescent assay and analysis of pharmacokinetic parameters with the PKBP-N1 program.Data from 13 cases were evaluable, 1 case being excluded due to an insufficient blood sample. Pharmacokinetics were consistent with the characteristics of the two-compartment model, parameters on days 1 and 14 being closely similar. The mean plasma maximal peak concentration (Cpmax) was 136.4 ± 89.4 μg/L, plasma distribution half-life time (T½α) was 0.071 ± 0.027 hours, plasma elimination half-life time (T½β) was 23.9 ± 18.4 hours, apparent distribution volume (Vd) was 335.1 ± 387.0L, entry distribution volume (Vc) was 20.3 ± 21.3 L, system clearance (CLs) was 8.65 ± 4.26 L/h, area under curve (AUC0-t) of concentration-time was 1128.5 ± 510.3 μg/h/L. From days 2 to 14, minimal steady state plasma drug concentration (Cssmin) was in the range of 31.7 ± 9.27 μg/L to 55.6 ± 32.3 μg/L for 10 detected patients.The data suggested that a two-compartment model most accurately reflects As₂O₃ pharmacokinetics in PHC patients. The apparent distribution volume was comparatively large and the plasma drug concentration was a little low, with a comparatively long drug elimination half-life, so clinical administration of the drug should be individualized for the best clinical efficacy and prevention of side effects.