Chapter 16

Routes of Excretion

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Hemodialysis or 'artificial kidney' therapy is used in renal failure to remove toxic waste material normally removed by the kidneys, from the patient's blood. In the procedure blood is diverted externally and allowed to flow across a semi-permeable membrane that is bathed with an aqueous isotonic solution. Small molecules including nitrogenous waste products and some drugs will diffuse from the blood, thus these compounds will be eliminated. Therefore in patients with kidney failure, hemodialysis may be an important route of drug elimination.

This technique is particularly important with drugs which:

  1. are smaller (< 500) molecular weight; and
  2. are not tightly bound to plasma protein;
  3. have a small apparent volume of distribution.
  4. have good water solubility;
Conversely drugs which are tightly bound or extensively stored or distributed into tissues are only poorly removed by this route, or process.

A simulation of drug concentration with and without dialysis is shown in Figure 16.3.1.

Figure 16.3.1 Drug Concentration before, during and after Low Flux Dialysis

Click on the figure to view the interactive graph

Low flux hemodialysis will readily remove molecules smaller than 500 Dalton. As the molecular weight increases to approximately 1000 Dalton the amount removed steadily decreases to insignificant. Thus clearance by hemodialysis falls from a maximum of about 4 L/hr to near zero with higher molecular weight compounds. Protein binding, represented by the fraction unbound (fu) will cause a proportional decrease in the hemodialysis clearance. Hemodialysis clearance is converted to a rate constant by dividing by the apparent volume distribution. This rate constant is added to the patient's elimination rate constant to give the increased, apparent rate constant during hemodialysis. As can be seen in Figure 16.3.1 this can cause an increased removal of a drug.

Table 16.3.1 Hemodialysis Clearance versus Drug Molecular Weight

Molecular Weight CLHemodialysis
Less than or equal to 500 Dalton fu x 4.0 L/hr
500 to 1000 Dalton CL(hemodialysis) versus Molecular Weight L/hr
Greater than 1000 Dalton 0.0 L/hr

This can be useful in cases where the concentration is too high but it can also complicate the maintenance of therapeutic concentrations. In Chapter 14 and 15 drug dosage regimens were calculated using elimination rate constant and volume of distribution. Hemodialysis can mean a significant increase in the amount of drug removed during the dialysis period. An additional dose maybe required. Later in this chapter we will adjust dosage regimens for reduced renal function according to Cpaverage or Cpmin/Cpmax requirements

Item 1. Hemodialysis may contribute significantly to the elimination of some drugs in patients with poor renal function. Explore the effect of molecular weight, protein binding and apparent volume of distribution on dialysis and explore the need for a post-dialysis dose. Explore the problem as a Linear Plot - Interactive graph.

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