Dialyzability of Drugs

Determining Impact of Dialysis on Drug Clearance

To determine the likelihood that dialysis will significantly impact clearance, consult the literature for information or the following may be used:

Key Criteria for Dialyzability

1. Apparent Unbound Volume of Distribution

Formula: Apparent unbound Vd (L/kg) = Vd (L/kg) / fraction unbound

Threshold: If this value is greater than 3.5 L/kg, an insignificant amount will probably be removed.

Clinical Note: Unbound volume of distributions 150 liters and above have less than 20% cleared during a four hour dialysis period. Only unbound drug can be dialyzed.

2. Total Clearance (Metabolic + Renal)

Threshold: If the medication's total clearance is above 10 mL/min/kg (600 mL/hr/kg, 42 L/hr for 70 kg patient), dialysis probably won't significantly increase clearance.

Rationale: Dialysis clearance is usually less than 150 mL/min (9 L/hr)

3. Molecular Weight

Low flux dialysis: If molecular weight is greater than 1,000 Daltons, low flux dialysis won't significantly impact clearance

High flux dialysis: If molecular weight is greater than 5,000 Daltons, high flux dialysis won't significantly impact clearance

Drugs Most Likely to be Removed by Hemodialysis

Drugs with the following characteristics are most likely to be removed by hemodialysis and will require extra dosing:

  • Low molecular weight
  • Limited volume of distribution
  • Water-soluble

Impact of Patient Weight on Dialysis Clearance

Clearance during dialysis is related to blood flow rate, dialysate flow rate, and filter. If the same flow rates and filter are used in patients of various weights, the fraction removed will be lower in higher-weight patients and higher in lower-weight patients, as the volume of distribution is proportional to body weight.

Fraction Eliminated During 4 Hour Dialysis vs. Weight
Hemodialysis elimination versus weight chart

Figure: Relationship between patient weight and fraction of drug eliminated during dialysis

Parameter Weight (kg)
40 50 60 70 80 90 100 110 120
Volume of Distribution 0.65 L/kg 26 32.5 39 45.5 52 58.5 65 71.5 78
Fraction Eliminated 0.46 0.39 0.34 0.30 0.27 0.24 0.22 0.20 0.19

Assumes: Clearance (L/hr) = (dialysis + renal) = 4.1 L/hr, Volume of Distribution = 0.65 L/kg

Fraction eliminated during 4 hour dialysis = 1 - exp(-(Cldialysis + Clrenal)/Vd × Length of Dialysis/Vd)

Calculation Formulas

Fraction of Amount in Body Lost During Dialysis Period

Formula 1:

Fraction eliminated = 1 - exp(-K(1/hr) during dialysis × Dialysis Period (hours))

Formula 2:

Fraction eliminated = 1 - exp(-((Cldialysis + Clrenal) / Vd) × Dialysis Period (hours))

Clinical Application

Dosing Adjustments for Hemodialysis Patients

When prescribing drugs for hemodialysis patients:

  1. Assess dialyzability using the three criteria above
  2. Consult drug-specific resources for dialysis dosing recommendations
  3. Consider patient weight when calculating fraction removed
  4. Time supplemental doses appropriately (typically after dialysis for dialyzable drugs)
  5. Monitor drug levels when available for optimal dosing