Pharmacokinetic Modeling and Dose Selection in a Randomized, Double-Blind, Placebo-Controlled Trial of a Human Recombinant Alkaline Phosphatase in Healthy Volunteers.

ABSTRACT:

Background and objective

Previous clinical trials have suggested that bovine intestinal alkaline phosphatase has renal protective effects in patients with sepsis-associated acute kidney injury. We conducted a first-in-human study to investigate the pharmacokinetics, safety and tolerability of a novel human recombinant alkaline phosphatase (recAP), and we developed a population pharmacokinetic model to support dose selection for future patient studies.

Methods

In a randomized, double-blind, placebo-controlled, phase I trial, healthy volunteers received a single dose of recAP (200, 500, 1000 or 2000 U/kg; n = 33; 3:1 ratio) or multiple doses of recAP (500 or 1000 U/kg; n = 18; 2:1 ratio) via a 1-h intravenous infusion on three consecutive days. Serum recAP concentrations, alka

SUBMITTER: Peters E 

PROVIDER: S-EPMC5021756 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature