Pharmacokinetic parameters of isoniazid obtained from 37 normal subjects were compared with parameters obtained from 14 patients with chronic renal failure. In the 29 normal rapid acetylators and eight normal slow acetylators, the mean plasma half-life values of isoniazid were 1.54 +/- 0.31 and 3.68 +/- 0.59 hours, respectively. The plasma half-life values of isoniazid in patients with chronic renal failure varied widely from 1.30 to 10.13 hours, but the values were significantly longer than those of normal subjects. Because isoniazid clearance is governed mainly by hepatic metabolism, such a significant prolongation of plasma half-life of isoniazid was unexpected; thus the pharmacokinetics of isoniazid were reevaluated in the same patients with chronic renal failure after the kidney transplantation. After successful kidney transplantation, the shortening of isoniazid half-life was pronounced and the nonrenal clearance was markedly increased. These findings indicate that decreased isoniazid clearance in chronic renal failure is caused in minor part by the decreased renal excretion of isoniazid and in major part by the depressed hepatic N-acetylation of isoniazid.

This article presents a novel method of dealing with disturbances and control saturation in the framework of discrete-time sliding mode control (DSMC). A DSMC with decoupled disturbance compensator (DDC) was developed for SMC to recover the loss of stability in the discrete-time domain. However, windup phenomena occur in both the switching function and the disturbance estimate when control saturation occurs, and the method cannot guarantee stability. The article develops a new method for maintaining stability under both disturbances and control saturation by incorporating a novel auxiliary state into the DSMC with DDC method. The auxiliary state prevents the windup phenomena, and the developed new method preserves the asymptotic convergence property of the disturbance estimation error dynamics and the stability of the sliding mode dynamics. Also, the error states are stable under bounded disturbances and control saturation. Simulations and experiments are performed on a commonly used industrial servo system to demonstrate the effectiveness of the proposed method. Index Terms-Discrete-time systems, sliding mode control (SMC), servosystems. I. INTRODUCTIONS LIDING mode control (SMC) is a special kind of variable structure control and is one of the most successful approaches in general control systems with bounded and matched disturbances. SMC drives the state variables to a predesigned sliding surface in a finite time and then keeps them on the sliding surface in the presence of the bounded disturbance. Therefore,

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