Valtrex Metabolism
No, Valtrex (valacyclovir) is not metabolized by the liver—it is rapidly converted to acyclovir by first-pass intestinal and/or hepatic metabolism, but acyclovir itself is not metabolized by cytochrome P450 enzymes and does not undergo significant hepatic metabolism. 1
Metabolic Pathway
Valacyclovir undergoes rapid first-pass conversion to acyclovir and L-valine through intestinal and/or hepatic metabolism, but this is enzymatic conversion, not traditional hepatic metabolism. 1, 2
- After oral administration, valacyclovir is nearly completely converted to acyclovir and the essential amino acid L-valine by first-pass intestinal and/or hepatic metabolism 1
- This conversion occurs rapidly, with plasma valacyclovir concentrations becoming non-quantifiable by 3 hours after administration 1
- Peak plasma valacyclovir concentrations are generally less than 0.5 mcg/mL at all doses 1
Acyclovir Metabolism
Acyclovir, the active metabolite, undergoes minimal metabolism and is not processed by liver cytochrome P450 enzymes. 1
- Acyclovir is converted to a small extent to inactive metabolites by aldehyde oxidase and by alcohol and aldehyde dehydrogenase 1
- Neither valacyclovir nor acyclovir is metabolized by cytochrome P450 enzymes 1
- More than 99% of radioactivity recovered in urine corresponds to acyclovir and its known metabolites, with valacyclovir accounting for less than 0.5% of the dose 2
Primary Route of Elimination
Acyclovir is eliminated primarily by the kidneys, not the liver. 1, 2
- Following oral administration of radiolabeled valacyclovir, 46% of administered radioactivity was recovered in urine and 47% in feces over 96 hours 1
- Acyclovir accounted for 89% of the radioactivity excreted in the urine 1
- Renal clearance of acyclovir represents 42% of total acyclovir apparent plasma clearance 1
Clinical Implications in Hepatic Impairment
No dose adjustment is required for patients with hepatic impairment, including those with cirrhosis. 1, 3
- Administration to subjects with moderate (biopsy-proven cirrhosis) or severe liver disease (with and without ascites and biopsy-proven cirrhosis) indicated that the rate but not the extent of conversion of valacyclovir to acyclovir is reduced 1
- The acyclovir half-life is not affected by hepatic impairment 1
- Dosage modification is not recommended for patients with cirrhosis 1
- No dosage adjustment is necessary in patients with impaired liver function 3
Renal Dosing Requirements
Dose reduction is required only in renal impairment, not hepatic disease. 1, 4
- In patients with end-stage renal disease (ESRD), the average acyclovir half-life is approximately 14 hours compared to 2.5-3.3 hours in normal renal function 1
- Approximately one-third of acyclovir is removed by dialysis during a 4-hour hemodialysis session 1
- Dosage adjustment is required in the presence of renal impairment due to primarily renal elimination 4