Problems in designing hemodialysis drug studies.

A clear understanding of the pharmacokinetics of a drug and of the proper methods for calculating dialyzer clearance is essential in designing hemodialysis studies. Hemodialysis should not begin until drug distribution is complete. Institution of dialysis prior to distribution equilibrium will result in increased removal of drug compared to what would be found in the clinical setting. All methods of calculating dialyzer clearance should be compared to that using total amount of drug recovered in the bath divided by the area under the drug concentration versus time curve during dialysis. To adequately probe the effect of the artificial kidney on drug concentrations sufficient plasma samples must be drawn postdialysis to define the rebound phenomena.