|
Metabolism After oral administration, valacyclovir hydrochloride is rapidly absorbed from the gastrointestinal tract. Valacyclovir is converted to acyclovir and L-valine by first-pass intestinal and/or hepatic metabolism. Acyclovir is converted to a small extent to inactive metabolites by aldehyde oxidase and by alcohol and aldehyde dehydrogenase. Neither valacyclovir nor acyclovir is metabolized by cytochrome P450 enzymes. Plasma concentrations of unconverted valacyclovir are low and transient, generally becoming non-quantifiable by 3 hours after administration. Peak plasma valacyclovir concentrations are generally less than 0.5 mcg/mL at all doses. After single-dose administration of 1 gram of VALTREX, average plasma valacyclovir concentrations observed were 0.5, 0.4, and 0.8 mcg/mL in patients with hepatic dysfunction, renal insufficiency, and in healthy volunteers who received concomitant cimetidine and probenecid, respectively. Text Continues Below
Elimination The pharmacokinetic disposition of acyclovir delivered by valacyclovir is consistent with previous experience from intravenous and oral acyclovir. Following the oral administration of a single 1-gram dose of radiolabeled valacyclovir to 4 healthy subjects, 45.60% and 47.12% of administered radioactivity was recovered in urine and feces over 96 hours, respectively. Acyclovir accounted for 88.60% of the radioactivity excreted in the urine. Renal clearance of acyclovir following the administration of a single 1-gram dose of VALTREX to 12 healthy volunteers was approximately 255 ± 86 mL/min which represents 41.9% of total acyclovir apparent plasma clearance. The plasma elimination half-life of acyclovir typically averaged 2.5 to 3.3 hours in all studies of VALTREX in volunteers with normal renal function. End-Stage Renal Disease (ESRD) Following administration of VALTREX to volunteers with ESRD, the average acyclovir half-life is approximately 14 hours. During hemodialysis, the acyclovir half-life is approximately 4 hours. Approximately one third of acyclovir in the body is removed by dialysis during a 4-hour hemodialysis session. Apparent plasma clearance of acyclovir in dialysis patients was 86.3 ± 21.3 mL/min/1.73 m 2 , compared to 679.16 ± 162.76 mL/min/1.73 m 2 in healthy volunteers.
Reduction in dosage is recommended in patients with renal impairment (see DOSAGE AND ADMINISTRATION). Page: << Prev | 1 | 2 | 3 | 4 | 5 | Next >>
|
.gif)
