Back to Search
Start Over
Quantification of serum levels in mice of seven drugs (and six metabolites) commonly taken by older people with polypharmacy
- Source :
- Fundamentalclinical pharmacologyReferences. 35(2)
- Publication Year :
- 2020
-
Abstract
- Polypharmacy (use of ≥ 5 drugs) is common in older people but has minimal preclinical or clinical evidence of safety or efficacy and is associated with adverse outcomes in older people. Drug-drug interactions are poorly understood beyond drug pairs. An efficient and sensitive method to measure multiple serum drugs and metabolites could inform drug dosing in polypharmacy. Development of a sensitive liquid chromatography - tandem mass spectrometry method to simultaneously measure seven drugs and their respective metabolites in serum in a preclinical model of polypharmacy. This method was validated for optimal recovery, matrix effect, limit of quantification (LOQ), inter- and intra-day variability, and carry over. Serum samples from mice (n = 5-6/group) treated with chronic oral doses of three polypharmacy regimens and five monotherapies were screened for drug and metabolite levels (metoprolol, α-hydroxymetoprolol, O-desmethylmetoprolol, omeprazole, 5-hydroxyomeprazole, omeprazole sulphone, acetaminophen, irbesartan, citalopram, oxybutynin, oxycodone, noroxycodone, oxymorphone and tenivastatin). The LOQ for the compounds ranged from 0.05 to 0.1 ng/mL in serum. Recovery, matrix effect, and inter- and intra-day variability peak response were acceptable. No carry over was observed at the concentrations tested. Analytes were detectable in mice treated with these drugs, and differences in drug levels were observed with different polypharmacy and monotherapy regimens. The method is sensitive and robust to measure parent drugs and metabolites simultaneously in the context of polypharmacy. Polypharmacy appeared to affect drug levels in a preclinical model. This model can be used to understand pharmacokinetics of chronic polypharmacy, which could inform prescribing and improve outcomes for older people.
- Subjects :
- Drug
media_common.quotation_subject
Metabolite
Frail Elderly
Context (language use)
Pharmacology
Citalopram
030226 pharmacology & pharmacy
03 medical and health sciences
chemistry.chemical_compound
Mice
0302 clinical medicine
Pharmacokinetics
Tandem Mass Spectrometry
medicine
Animals
Humans
Pharmacology (medical)
Drug Interactions
Omeprazole
media_common
Acetaminophen
Polypharmacy
Aged, 80 and over
business.industry
Reproducibility of Results
chemistry
business
Oxycodone
030217 neurology & neurosurgery
medicine.drug
Chromatography, Liquid
Metoprolol
Subjects
Details
- ISSN :
- 14728206
- Volume :
- 35
- Issue :
- 2
- Database :
- OpenAIRE
- Journal :
- Fundamentalclinical pharmacologyReferences
- Accession number :
- edsair.doi.dedup.....a66b33361382607eb7ca09390064beb0