Pharmacodynamic analysis of intravenous recombinant urate oxidase using an indirect pharmacological response model in healthy subjects.

ABSTRACT:

Aim

Pharmacodynamic analysis of intravenous recombinant urate oxidase produced by Escherichia coli was performed in healthy subjects using a pharmacokinetic/pharmacodynamic (PK/PD) model.

Methods

A randomized, single-blind, placebo-controlled study was performed in 40 healthy Chinese subjects (4 groups of 10 subjects each, placebo 4:1 ratio) who received infusions of uricase (single doses of 0.1, 0.2, and 0.3 mg/kg; multiple doses of 0.2 mg·kg(-1)·d(-1) for 7 d). PK profiles were determined through plasma uricase activity, and PD profiles were established using uric acid levels in plasma and urine. The plasma PD parameter was estimated as changes in plasma uric acid levels as the effect in the indirect response model. Adverse events were also monitored.

Results

A two-

SUBMITTER: Cai NF 

PROVIDER: S-EPMC4220074 | biostudies-literature | 2014 Nov

REPOSITORIES: biostudies-literature