Premium
Clinical trial: single‐ and multiple‐dose pharmacokinetics of polyethylene glycol (PEG‐3350) in healthy young and elderly subjects
Author(s) -
PELHAM R. W.,
NIX L. C.,
CHAVIRA R. E.,
CLEVELAND M. VB.,
STETSON P.
Publication year - 2008
Publication title -
alimentary pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.308
H-Index - 177
eISSN - 1365-2036
pISSN - 0269-2813
DOI - 10.1111/j.1365-2036.2008.03727.x
Subject(s) - pharmacokinetics , peg ratio , medicine , urine , polyethylene glycol , excretion , dosing , pharmacology , liter , high performance liquid chromatography , pegylation , chromatography , chemistry , biochemistry , finance , economics
Summary Background The pharmacokinetics of polyethylene glycol 3350 (PEG‐3350) have not been fully described because of lack of a sufficiently sensitive analytical method. Aim To describe the pharmacokinetics of PEG‐3350 in humans. Methods A highly sensitive, high performance liquid chromatography with mass spectrometry (HPLC/MS/MS) method was developed for PEG‐3350 in urine, plasma and faeces with quantification limits of 30 ng/mL, 100 ng/mL and 500 μg/g respectively. Noncompartmental pharmacokinetics methods were used and the effects of gender, age, renal status and dosing frequency were examined after the oral administration of 17 g to healthy volunteers. Results Peak PEG‐3350 plasma concentrations occurred at 2–4 h and declined to nonquantifiable levels usually within 18 h after single and multiple doses, with a half‐life of about 4–6 h. Steady state was reached within 5 days of dosing. Mean urinary excretion of the administered dose ranged from 0.19% to 0.25%. Age, gender or mild kidney impairment did not alter the pharmacokinetics of PEG‐3350. Mean faecal excretion of the administered dose was 93% in young subjects. Conclusions For the first time, a highly sensitive assay allowed comprehensive pharmacokinetics studies of PEG‐3350 in humans. These studies confirmed that orally administered PEG‐3350 is minimally absorbed, rapidly excreted and primarily eliminated via faeces.