Valtrex

[Valacyclovir]

Clinical Pharmacology
CLINICAL PHARMACOLOGY

After oral administration, valacyclovir hydrochloride is rapidly absorbed from the gastrointestinal tract and nearly completely converted to acyclovir and L-valine by first-pass intestinal and/or hepatic metabolism.

Pharmacokinetics

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The pharmacokinetics of valacyclovir and acyclovir after oral administration of VALTREX have been investigated in 14 volunteer studies involving 283 adults.

Absorption and Bioavailability

The absolute bioavailability of acyclovir after administration of VALTREX is 54.5% ± 9.1% as determined following a 1-gram oral dose of VALTREX and a 350-mg intravenous acyclovir dose to 12 healthy volunteers. Acyclovir bioavailability from the administration of VALTREX is not altered by administration with food (30 minutes after an 873 Kcal breakfast, which included 51 grams of fat).

There was a lack of dose proportionality in acyclovir maximum concentration (Cmax) and area under the acyclovir concentration-time curve (AUC) after single-dose administration of 100 mg,
250 mg, 500 mg, 750 mg, and 1 gram of VALTREX to 8 healthy volunteers. The mean Cmax ( SD) was 0.83 ( 0.14), 2.15 ( 0.50), 3.28 (± 0.83), 4.17 ( 1.14), and 5.65 ( 2.37) mcg/mL, respectively; and the mean AUC ( SD) was 2.28 ( 0.40), 5.76 ( 0.60), 11.59 ( 1.79), 14.11 (± 3.54), and 19.52 ( 6.04) hr•mcg/mL, respectively.

There was also a lack of dose proportionality in acyclovir Cmax and AUC after the multiple-dose administration of 250 mg, 500 mg, and 1 gram of VALTREX administered 4 times daily for 11 days in parallel groups of 8 healthy volunteers. The mean Cmax ( SD) was 2.11 (± 0.33), 3.69 ( 0.87), and 4.96 ( 0.64) mcg/mL, respectively, and the mean AUC ( SD) was 5.66 ( 1.09), 9.88 ( 2.01), and 15.70 ( 2.27) hr•mcg/mL, respectively. There is no accumulation of acyclovir after the administration of valacyclovir at the recommended dosage regimens in healthy volunteers with normal renal function. Distribution: The binding of valacyclovir to human plasma proteins ranged from 13.5% to 17.9%.

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