Pharmacokinetics of trace elements by noncompartmental analysis in rats. Part 1. Significance of the pharmacokinetic parameters.

Abstract

Six-week-old male Wistar rats were administrated the radioisotopes of five trace elements (iron, zinc, copper, manganese and iodine) intravenously in order to elucidate the significance of their pharmacokinetics by noncompartmental analysis. The mean residence time (MRT) and variance of residence time (VRT) increased in the order Mn, Cu, I, Fe and Zn. Neither MRT nor VRT indicated any statistical significance between I and Fe. These results suggested that Mn and Cu were voided rapidly from the plasma, whereas Zn persisted in the plasma for the longest time among these elements. Though I and Fe showed quite different plasma disappearance curves, both were considered to diminish at almost the same speed. The volume of distribution at steady state (Vdss) increased in the order Cu (32 ml), Fe (62 ml), I (149 ml), Mn (185 ml) and Zn (1012 ml). The distribution coefficient (Kd) of these elements increased in the same order as Vdss did. For Cu and Fe, Vdss was intermediate between the plasma volume and total body fluid volume of the rat, while, for the others, Vdss was greater than the total body fluid volume. In particular, Vdss of Zn was the greatest among these elements. Hence, the present study suggested that the plasma concentrations of Cu and Fe may reflect their body contents fairy well, though those of I, Fe and Zn can hardly do so. Vdss and Kd are, therefore, considered to be useful as supplementary diagnostic indices to understand the plasma concentrations of trace elements. Systemic clearance (CLs) increased in the order Fe (0.02 ml/min), Zn (0.07 ml/min), I (0.21 ml/min), Cu (0.37 ml/min) and Mn (4.61 ml/min). The CLs of Mn was similar to the hepatic plasma flow rate of the rat in size, indicating that the Cls of Mn may be one of the greatest among trace elements. It appeared, therefore, that when administered intravenously, Mn may be transferred from the plasma to the tissues more easily than the other elements.