Clinical trial: single‐ and multiple‐dose pharmacokinetics of polyethylene glycol (PEG‐3350) in healthy young and elderly subjects

• Published in: Alimentary pharmacology & therapeutics Vol. 28; no. 2; pp. 256 - 265
• Main Authors: PELHAM, R. W., NIX, L. C., CHAVIRA, R. E., CLEVELAND, M. VB, STETSON, P.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.07.2008; Blackwell
• Subjects: Adult; Age Factors; Aged; Biological and medical sciences; Chromatography, High Pressure Liquid - methods; Digestive system; Female; Gastroenterology. Liver. Pancreas. Abdomen; Humans; Male; Mass Spectrometry - methods; Medical sciences; Middle Aged; Pharmacology. Drug treatments; Polyethylene Glycols - administration & dosage; Polyethylene Glycols - pharmacokinetics; Sex Factors; Multiple dose; Ethylene oxide polymer; Human; Single dose; Clinical trial; Pharmacokinetics; Elderly
• ISSN: 0269-2813; 1365-2036
• DOI: 10.1111/j.1365-2036.2008.03727.x

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.