Pharmacokinetics and phenotyping properties of the "Basel" phenotyping cocktail combination capsule in healthy male adults

Suenderhauf, Claudia and Berger, Benjamin and Puchkov, Maxim and Schmid, Yasmin and Müller, Sabine and Huwyler, Jörg and Haschke, Manuel and Krähenbühl, Stephan and Duthaler, Urs. (2020) Pharmacokinetics and phenotyping properties of the "Basel" phenotyping cocktail combination capsule in healthy male adults. British journal of clinical pharmacology, 86 (2). pp. 352-361.

Full text not available from this repository.

Official URL: https://edoc.unibas.ch/74114/

Downloads: Statistics Overview


We compared the phenotyping metrics of a combination capsule formulation to its individual components of the newly composed "Basel" phenotyping cocktail. Moreover, we investigated a reduced sampling regimen for clinical applications.; We performed in vitro experiments and a crossover pharmacokinetic study in twelve healthy male subjects to compare the "Basel" phenotyping cocktail capsule containing 6 cytochrome P450 (CYP) probe drugs with individual administration of the same drugs. Parent compounds and selected metabolites were determined by LC-MS/MS. Metabolic ratios (MR) for AUC and single time point measurements and their correlation were determined.; Experiments with human liver microsomes and primary human hepatocytes in 3D co-culture confirmed that flurbiprofen is a suitable CYP2C9 substrate. Both cocktail formulations (capsule and individual probe drug administration) were well-tolerated and yielded reproducible MRs, which were almost identical. Correlations between single time point ratios and the corresponding AUC ratios depended on the sampling time point and the concentration time curve of the probe drugs. The MR of the capsule (Spearman rank correlation coefficient, R; s; : 0.77-0.97) as well as the individual components (R; s; : 0.69-0.99) correlated best at 6 h post treatment considering all six CYPs. Moreover, the 2 h time points of the capsule agreed suitably with the AUC, however the MR of omeprazole could not be determined for 10 out of 12 subjects.; The capsule is easy to swallow, well tolerated, and provides reliable estimates for CYP activity. The optimal sampling point for the capsule formulation is 6 hours after intake.
Faculties and Departments:05 Faculty of Science > Departement Pharmazeutische Wissenschaften > Pharmazie > Pharmaceutical Technology (Huwyler)
UniBasel Contributors:Huwyler, Jörg and Puchkov, Maxim
Item Type:Article, refereed
Article Subtype:Research Article
Note:Publication type according to Uni Basel Research Database: Journal article
Identification Number:
Last Modified:22 Dec 2020 11:23
Deposited On:22 Dec 2020 11:23

Repository Staff Only: item control page