Factors affect drug dialyzability
The extent to which a drug is affected by dialysis is determined primarily by several physicochemical characteristics of the drug, which are briefly described in the text that follows.
These include molecular size, protein binding, and volume of distribution, water solubility, and plasma clearance.
In addition to these properties of the drug, technical aspects of the dialysis procedure may also determine the extent to which a drug is removed by dialysis
Dialysis is dependent upon the use of a dialytic membrane: either a synthetic membrane with fixed pore size, as in hemodialysis, or a naturally occurring peritoneal membrane, as in peritoneal dialysis.
The movement of drugs or other solutes is largely determined by the size of these molecules in relation to the pore size of the membrane.
As a general rule, smaller molecular weight substances will pass through the membrane more easily than larger molecular weight substances.
A common assumption is that pore size of the peritoneal membrane is somewhat larger than that of the hemodialysis membrane; this would explain the observation that larger molecular weight substances appear to cross the peritoneal membrane to a greater extent than they cross the hemodialysis membrane.
Protein binding another important factor determining drug dialyzability is the concentration gradient of unbound (free) drug across the dialysis membrane.
Drugs with a high degree of protein binding will have a small plasma concentration of unbound drug available for dialysis. Uremia may have an effect on protein binding for some drugs. Through mechanisms not completely understood, protein binding may decrease in uremic serum.
Should this change in binding be substantial, increased dialyzability of free drug may occur.
Because the primary binding proteins for most drugs (albumin, ?1-acid glycoprotein) are of large molecular size, the drug-protein complex is often too large to cross the dialysis membrane, especially in the case of the hemodialysis membrane. Since the peritoneal membrane does permit the passage of some proteins, there may be some limited drug-protein removal with this technique.
Increased protein concentrations have been noted in peritoneal effluent during episodes of peritonitis.
Volume of Distribution
A drug with a large volume of distribution is distributed widely throughout tissues and is present in relatively small amounts in the blood.
Factors that contribute to a drug having a large volume of distribution include a high degree of lipid solubility and low plasma protein binding.
Drugs with a large volume of distribution are likely to be minimally dialyzed.
The dialysate used for either hemodialysis or peritoneal dialysis is an aqueous solution.
In general, drugs with high water solubility will be dialyzed to a greater extent than those with high lipid solubility.
Highly lipid-soluble drugs tend to be distributed throughout tissues, and therefore only a small fraction of the drug is present in plasma and accessible for dialysis.
The inherent metabolic clearance, the sum of renal and nonretail clearance of a drug, is often termed the �plasma clearance� of a drug.
In dialysis patients, renal clearance is largely replaced by dialysate clearance.
If, for a particular drug, nonretail clearance is large compared to renal clearance, the contribution dialysis may make to total drug removal is low.
However, if renal (dialysis) clearance increases plasma clearance by 30% or more, dialysis clearance is considered to be clinically important.
As mentioned previously, the characteristics of the dialysis membrane determine to a large extent the dialysis of drugs. Pore size, surface area, and geometry are the primary determinants of the performance of a given membrane.
The technology of hemodialysis continues to evolve, and new membranes continue to be introduced for clinical use.
Interpretation of published literature should be tempered with the understanding that newer membranes may have different drug dialysis characteristics.
On the other hand, because the peritoneal membrane is natural, little can be done to alter its characteristics.
Blood and Dialysate Flow Rates
The hemodialysis prescription contains a determination of blood and dialysate flow rates.
As drugs normally move from blood to dialysate, the flow rates of these two substances may have a pronounced effect on dialyzability.
In general, increased blood flow rates during hemodialysis will enable greater amounts of drug to be delivered to the dialysis membrane.
As concentrations of drug increase in the dialysate, the flow rate of the dialysis solution also becomes important in overall drug removal.
Greater dialysis can be achieved with faster dialysate flow rates that keep dialysate drug concentrations at a minimum.
During peritoneal dialysis, little can be done to alter blood flow rates to the peritoneum.
However, dialysate flow rates are determined by the volume and frequency of dialysate exchange in the peritoneum.
At low exchange rates, drug concentrations in the dialysate will increase during the period of time in which the dialysate resides in the peritoneal cavity, thus slowing additional movement of drug across the membrane.
More frequent exchanges will favor increased drug dialyzability, provided the drugs physicochemical characteristics permit its movement across the peritoneal membrane.