Acyclovir kinetics in end-stage renal disease

Area of Science:

• Pharmacokinetics
• Nephrology
• Internal Medicine

Background:

• Acyclovir (ACV) is primarily eliminated by the kidneys, with a normal plasma half-life of 2-3 hours.
• Severe renal failure markedly impacts drug clearance, necessitating studies on drug kinetics in these patients.

Purpose of the Study:

• To investigate the pharmacokinetics and tolerance of acyclovir in anuric patients undergoing long-term hemodialysis.
• To determine the impact of renal failure and hemodialysis on acyclovir elimination.

Main Methods:

• Six anuric subjects received a 1-hour infusion of 2.5 mg/kg intravenous acyclovir.
• Plasma acyclovir concentrations were measured over time.
• Hemodialysis was performed, and acyclovir clearance during dialysis was assessed.

Main Results:

• Acyclovir's terminal plasma half-life extended to 19.5 hours in anuric subjects.
• Total body clearance was significantly reduced (28.6 ml/min/1.73 m2).
• Acyclovir was readily removed by hemodialysis, with a clearance of 81.8 ml/min and a 0.45 extraction coefficient.
• No acyclovir-related adverse effects were observed.

Conclusions:

• Acyclovir elimination is substantially impaired in end-stage renal failure.
• Hemodialysis effectively clears acyclovir, but requires careful consideration for dosage adjustments.
• Dosage modifications are essential to prevent acyclovir accumulation and account for drug removal during hemodialysis.