Pharmacokinetics of TKM-130803 in Sierra Leonean patients with Ebola virus disease:  plasma concentrations exceed target levels, with drug accumulation in the most severe patients.

ABSTRACT:

Background

TKM-130803 is a specific anti-EBOV therapeutic comprised of two small interfering RNAs (siRNA) siLpol-2 and siVP35-2. The pharmacokinetics (PK) of these siRNAs was defined in Ebola virus disease (EVD) patients, with reference to efficacy (ET) and toxicology thresholds (TT). The relationship between PK and patient survival was explored.

Methods

Pharmacokinetic (PK) and pharmacodynamic (PD) data were available for seven participants with EVD in Sierra Leone who received 0·3 mg/kg of TKM-130803 by intravenous infusion over 2 h daily for up to 7 days. Plasma concentration of siRNA was compared to survival at 14 days. PK data were fitted to two-compartment models then Monte Carlo simulated PK profiles were compared to ET (Cmax 0·04-0·57 ng/mL and mean concentration 1·4

SUBMITTER: Scott JT 

PROVIDER: S-EPMC7033524 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature