Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-19282
Tomalik-Scharte, D; Lütjohann, D; Doroshyenko, O; Frank, D; Jetter, A; Fuhr, U (2009). Plasma 4beta-Hydroxycholesterol: An Endogenous CYP3A Metric? Clinical Pharmacology and Therapeutics, 86(2):147-153.
View at publisher
- Registered users only
We assessed the suitability of 4beta-hydroxycholesterol (4betaOH-C) as an endogenous cytochrome P450 3A (CYP3A) phenotyping metric. 4betaOH-C and its ratio to cholesterol (4betaOH-C/C) were determined in five cocktail phenotyping studies, with and without co-medication with a potential CYP3A inhibitor. These parameters were compared with established midazolam-based CYP3A metrics: clearance after intravenous (i.v.) administration (M-Cl) and apparent clearance after oral administration (M-Cl/F), reflecting hepatic and overall activity, respectively. In a common evaluation of periods without co-medication, there was a slight positive correlation of 4betaOH-C and 4betaOH-C/C with midazolam metrics: M-Cl (r = 0.239 and 0.348, respectively) and M-Cl/F (r = 0.267 and 0.353, respectively); P (one-sided) < 0.05. Co-medication with lopinavir/ritonavir caused a strong decrease in midazolam metrics and a mild decrease in cholesterol metrics. However, the intake of propiverine resulted in opposite trends for midazolam-based and cholesterol-based metrics. The information currently available does not justify the use of 4betaOH-C for estimation of basal CYP3A activity. Further studies to address the temporal variations in local CYP3A activity are needed to assess its role as a biomarker during CYP3A inhibition.Clinical Pharmacology & Therapeutics (2009); advance online publication 20 May 2009. doi:10.1038/clpt.2009.72.
417 downloads since deposited on 17 Jun 2009
28 downloads since 12 months
|Item Type:||Journal Article, refereed, original work|
|Communities & Collections:||04 Faculty of Medicine > University Hospital Zurich > Clinic for Clinical Pharmacology and Toxicology|
|Dewey Decimal Classification:||610 Medicine & health|
|Deposited On:||17 Jun 2009 08:23|
|Last Modified:||17 Jul 2014 20:47|
|Publisher:||Nature Publishing Group|
Users (please log in): suggest update or correction for this item
Repository Staff Only: item control page