Gibson et al. (Kidney Int 1977; 12: 422) studied the clearance of procainamide in volunteers with normal renal function and in patients with end-stage renal failure. The authors found the Clr, Clm, and the apparent volume of distribution to be 0 mL/min/kg, 1.46 mL/min/kg, and 1.67 L/kg, respectively, in patients with end-stage renal failure. Determine the elimination half-life of procainamide in patients.
The Correct Answer and Explanation is:
To calculate the elimination half-life (t₁/₂) of procainamide in patients with end-stage renal failure, we need to use the following equation derived from pharmacokinetics:t1/2=0.693×VdCltotalt_{1/2} = \frac{0.693 \times V_d}{Cl_{total}}t1/2=Cltotal0.693×Vd
Where:
- t1/2t_{1/2}t1/2 is the elimination half-life.
- VdV_dVd is the apparent volume of distribution.
- CltotalCl_{total}Cltotal is the total clearance (which is the sum of renal clearance ClrCl_rClr and metabolic clearance ClmCl_mClm).
Given Data:
- Clr=0 mL/min/kgCl_r = 0 \, \text{mL/min/kg}Clr=0mL/min/kg (renal clearance)
- Clm=1.46 mL/min/kgCl_m = 1.46 \, \text{mL/min/kg}Clm=1.46mL/min/kg (metabolic clearance)
- Vd=1.67 L/kgV_d = 1.67 \, \text{L/kg}Vd=1.67L/kg (apparent volume of distribution)
The total clearance CltotalCl_{total}Cltotal is the sum of renal and metabolic clearances:Cltotal=Clr+Clm=0+1.46=1.46 mL/min/kgCl_{total} = Cl_r + Cl_m = 0 + 1.46 = 1.46 \, \text{mL/min/kg}Cltotal=Clr+Clm=0+1.46=1.46mL/min/kg
Now, converting the clearance from mL/min/kg to L/min/kg (since VdV_dVd is in L/kg):1.46 mL/min/kg=0.00146 L/min/kg1.46 \, \text{mL/min/kg} = 0.00146 \, \text{L/min/kg}1.46mL/min/kg=0.00146L/min/kg
Substituting into the half-life formula:
t1/2=0.693×1.670.00146t_{1/2} = \frac{0.693 \times 1.67}{0.00146}t1/2=0.001460.693×1.67t1/2=1.157310.00146=793.69 minutest_{1/2} = \frac{1.15731}{0.00146} = 793.69 \, \text{minutes}t1/2=0.001461.15731=793.69minutes
Thus, the elimination half-life of procainamide in patients with end-stage renal failure is approximately 793.69 minutes, or roughly 13.23 hours.
Explanation:
The half-life of a drug reflects how long it takes for the concentration of the drug in the body to reduce by half. In patients with end-stage renal failure, the elimination of the drug is primarily governed by the liver’s metabolic clearance because renal clearance is essentially zero. The calculated half-life is significantly longer compared to individuals with normal renal function, where the kidneys contribute more to drug clearance.
This long half-life indicates that procainamide may accumulate in the body in patients with end-stage renal failure, requiring dose adjustments to avoid toxicity.
