Pharmacokinetic Study Of Valaciclovir Hydrochloride Tablets

GlaxoSmithKline18 enrolled

Overview

Valaciclovir (VACV), the L-valyl ester prodrug of aciclovir (ACV), is extensively converted to ACV and L-valine after oral administration. In subjects with normal renal function, ACV is predominantly eliminated unchanged in the urine, with a small proportion metabolized to 9-carboxymethoxymethylguanine (CMMG). The metabolism of ACV to CMMG is thought to involve aldehyde dehydrogenase (ALDH). On the basis of a high proportion of the Japanese population having low-activity ALDH, it can be hypothesized that the conversion of ACV to CMMG is decreased, thereby leading, in patients with renal impairment, to higher plasma concentrations of ACV. This pilot study was conducted to investigate potential relationships between genetic polymorphisms of ALDH2, an isozyme of ALDH, and the plasma pharmacokinetics (PK) of VACV, ACV and CMMG in subjects with end-stage renal disease on hemodialysis.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Virus Diseases

Interventions

Eligibility

Sex: ALLMin age: 20 Years

Medical Language ↔ Plain English

Inclusion criteria: * Japanese subjects with chronic renal failure undergoing hemodialysis regularly three times a week for at least 12 weeks prior to the start of the study. Exclusion criteria: * Subjects with current alcohol dependence. * Subjects with gastrointestinal dysfunction that may affect drug absorption. * Subjects who have received an organ transplant (However, subjects with a corneal transplant or any other organ transplant that may not affect the objectives of the study will be eligible for inclusion in this study).

Outcomes

Primary Outcomes

- The pharmacokinetic parameters for VACV, ACV and CMMG - Relationship between ALDH2 genotypes and the pharmacokinetics of VACV, ACV and CMMG in blood

Secondary Outcomes

- Change in blood ACV and CMMG concentrations after a 4-hour hemodialysis session - Safety (adverse events occurring during the study, clinical laboratory tests)