Perspective: 4β-hydroxycholesterol as an emerging endogenous biomarker of hepatic CYP3A

References

• Aitken AE, Richardson TA, Morgan ET. (2006). Regulation of drug-metabolizing enzymes and transporters in inflammation. Annu Rev Pharmacol Toxicol 46:123–149.
   PubMed Web of Science ®Google Scholar
• Aubry AF, Dean B, Diczfalusy U, et al. (2016). Recommendations on the development of a bioanalytical assay for 4beta-hydroxycholesterol, an emerging endogenous biomarker of CYP3A activity. AAPS J. 18:1056–1066.
   PubMed Web of Science ®Google Scholar
• Benet LZ. (2005). There are no useful CYP3A probes that quantitatively predict the in vivo kinetics of other CYP3A substrates and no expectation that one will be found. Mol Interv 5:79–83.
   PubMed Web of Science ®Google Scholar
• Bjorkhem-Bergman L, Backstrom T, Nylen H, et al. (2013). Comparison of endogenous 4beta-hydroxycholesterol with midazolam as markers for CYP3A4 induction by rifampicin. Drug Metab Dispos 41:1488–1493.
   PubMed Web of Science ®Google Scholar
• Bjorkhem-Bergman L, Backstrom T, Nylen H, et al. (2014). Quinine compared to 4beta-hydroxycholesterol and midazolam as markers for CYP3A induction by rifampicin. Drug Metab Pharmacokinet 29:352–355.
   PubMed Web of Science ®Google Scholar
• Bjorkhem I. (2002). Do oxysterols control cholesterol homeostasis? J Clin Invest 110:725–730.
   PubMed Web of Science ®Google Scholar
• Bodin K, Andersson U, Rystedt E, et al. (2002). Metabolism of 4 beta-hydroxycholesterol in humans. J Biol Chem 277:31534–31540.
   PubMed Web of Science ®Google Scholar
• Bodin K, Bretillon L, Aden Y, et al. (2001). Antiepileptic drugs increase plasma levels of 4beta-hydroxycholesterol in humans: evidence for involvement of cytochrome p450 3A4. J Biol Chem 276:38685–38689.
   PubMed Web of Science ®Google Scholar
• Breuer O. (1995). Identification and quantitation of cholest-5-ene-3 beta,4 beta-diol in rat liver and human plasma. J Lipid Res 36:2275–2281.
   PubMed Web of Science ®Google Scholar
• Breuer O, Dzeletovic S, Lund E, Diczfalusy U. (1996). The oxysterols cholest-5-ene-3 beta,4 alpha-diol, cholest-5-ene-3 beta,4 beta-diol and cholestane-3 beta,5 alpha,6 alpha-triol are formed during in vitro oxidation of low-density lipoprotein, and are present in human atherosclerotic plaques. Biochim Biophys Acta 1302:145–152.
   PubMed Web of Science ®Google Scholar
• Brown AJ, Dean RT, Jessup W. (1996). Free and esterified oxysterol: Formation during copper-oxidation of low-density lipoprotein and uptake by macrophages. J Lipid Res 37:320–335.
   PubMed Web of Science ®Google Scholar
• Chang TY, Chang CC, Ohgami N, Yamauchi Y. (2006). Cholesterol sensing, trafficking, and esterification. Annu Rev Cell Dev Biol 22:129–157.
   PubMed Web of Science ®Google Scholar
• Cheng PY, Morgan ET. (2001). Hepatic cytochrome P450 regulation in disease states. Curr Drug Metab 2:165–183.
   PubMed Web of Science ®Google Scholar
• Diczfalusy U, Kanebratt KP, Bredberg E, et al. (2009). 4beta-hydroxycholesterol as an endogenous marker for CYP3A4/5 activity. Stability and half-life of elimination after induction with rifampicin. Br J Clin Pharmacol 67:38–43.
   PubMed Web of Science ®Google Scholar
• Diczfalusy U, Miura J, Roh HK, et al. (2008). 4Beta-hydroxycholesterol is a new endogenous CYP3A marker: relationship to CYP3A5 genotype, quinine 3-hydroxylation and sex in Koreans, Swedes and Tanzanians. Pharmacogenet Genomics 18:201–208.
   PubMed Web of Science ®Google Scholar
• Dutreix C, Lorenzo S, Wang Y. (2014). Comparison of two endogenous biomarkers of CYP3A4 activity in a drug-drug interaction study between midostaurin and rifampicin. Eur J Clin Pharmacol 70:915–920.
   PubMed Web of Science ®Google Scholar
• Dutreix C, Munarini F, Lorenzo S, et al. (2013). Investigation into CYP3A4-mediated drug–drug interactions on midostaurin in healthy volunteers. Cancer Chemother Pharmacol 72:1223–1234.
   PubMed Web of Science ®Google Scholar
• Fakhoury M, Lecordier J, Medard Y, et al. (2006). Impact of inflammation on the duodenal mRNA expression of CYP3A and P-glycoprotein in children with Crohn’s disease. Inflamm Bowel Dis 12:745–749.
   PubMed Web of Science ®Google Scholar
• Food and drug administration. (2012). Guidance for industry: Drug interaction studies-study design, data analysis, implications for dosing, and labeling recommendations. Available from: http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm292362.pdf.
   Google Scholar
• Gebeyehu E, Engidawork E, Bijnsdorp A, et al. (2011). Sex and CYP3A5 genotype influence total CYP3A activity: high CYP3A activity and a unique distribution of CYP3A5 variant alleles in Ethiopians. Pharmacogenomics J 11:130–137.
   PubMed Web of Science ®Google Scholar
• Gjestad C, Huynh DK, Haslemo T, Molden E. (2016). 4beta-hydroxycholesterol correlates with dose but not steady-state concentration of carbamazepine: indication of intestinal CYP3A in biomarker formation?. Br J Clin Pharmacol 81:269–276.
   PubMed Web of Science ®Google Scholar
• Goodenough AK, Onorato JM, Ouyang Z, et al. (2011). Quantification of 4-beta-hydroxycholesterol in human plasma using automated sample preparation and LC-ESI-MS/MS analysis. Chem Res Toxicol 24:1575–1585.
   PubMed Web of Science ®Google Scholar
• Habtewold A, Amogne W, Makonnen E, et al. (2013). Pharmacogenetic and pharmacokinetic aspects of CYP3A induction by efavirenz in HIV patients. Pharmacogenomics J 13:484–489.
   PubMed Web of Science ®Google Scholar
• Iwamoto J, Saito Y, Honda A, et al. (2013). Bile acid malabsorption deactivates pregnane X receptor in patients with Crohn’s disease. Inflamm Bowel Dis 19:1278–1284.
   PubMed Web of Science ®Google Scholar
• Johnson TN, Tanner MS, Taylor CJ, Tucker GT. (2001). Enterocytic CYP3A4 in a paediatric population: Developmental changes and the effect of coeliac disease and cystic fibrosis. Br J Clin Pharmacol 51:451–460.
   PubMed Web of Science ®Google Scholar
• Josephson F, Bertilsson L, Bottiger Y, et al. (2008). CYP3A induction and inhibition by different antiretroviral regimens reflected by changes in plasma 4beta-hydroxycholesterol levels. Eur J Clin Pharmacol 64:775–781.
   PubMed Web of Science ®Google Scholar
• Kanebratt KP, Diczfalusy U, Backstrom T, et al. (2008). Cytochrome P450 induction by rifampicin in healthy subjects: Determination using the Karolinska cocktail and the endogenous CYP3A4 marker 4beta-hydroxycholesterol. Clin Pharmacol Ther 84:589–594.
   PubMed Web of Science ®Google Scholar
• Kasichayanula S, Boulton DW, Luo WL, et al. (2014). Validation of 4β-hydroxycholesterol and evaluation of other endogenous biomarkers for the assessment of CYP3A activity in healthy subjects. Br J Clin Pharmacol 78:1122–1134.
   PubMed Web of Science ®Google Scholar
• Kaukonen KM, Olkkola KT, Neuvonen PJ. (1997). Itraconazole increases plasma concentrations of quinidine. Clin Pharmacol Ther 62:510–517.
   PubMed Web of Science ®Google Scholar
• Keubler A, Weiss J, Haefeli WE, et al. (2012). Drug interaction of efavirenz and midazolam: efavirenz activates the CYP3A-mediated midazolam 1′-hydroxylation in vitro. Drug Metab Dispos 40:1178–1182.
   PubMed Web of Science ®Google Scholar
• Kharasch ED, Thummel KE, Watkins PB. (2005). CYP3A probes can quantitatively predict the in vivo kinetics of other CYP3A substrates and can accurately assess CYP3A induction and inhibition. Mol Interv 5:151–153.
   PubMed Web of Science ®Google Scholar
• Lamba JK, Lin YS, Schuetz EG, Thummel KE. (2002). Genetic contribution to variable human CYP3A-mediated metabolism. Adv Drug Deliv Rev 54:1271–1294.
   PubMed Web of Science ®Google Scholar
• Leil TA, Kasichayanula S, Boulton DW, Lacreta F. (2014). Evaluation of 4beta-hydroxycholesterol as a clinical biomarker of CYP3A4 drug interactions using a bayesian mechanism-based pharmacometric model. CPT Pharmacometrics Syst Pharmacol 3:e120.
   PubMedGoogle Scholar
• Lin CY, Morel DW. (1996). Esterification of oxysterols in human serum: effects on distribution and cellular uptake. J Lipid Res 37:168–178.
   PubMed Web of Science ®Google Scholar
• Lutjohann D, Marinova M, Schneider B, et al. (2009). 4beta-hydroxycholesterol as a marker of CYP3A4 inhibition in vivo – effects of itraconazole in man. Int J Clin Pharmacol Ther 47:709–715.
   PubMed Web of Science ®Google Scholar
• Marde Arrhen Y, Nylen H, Lovgren-Sandblom A, et al. (2013). A comparison of 4beta-hydroxycholesterol: Cholesterol and 6beta-hydroxycortisol: Cortisol as markers of CYP3A4 induction. Br J Clin Pharmacol 75:1536–1540.
   PubMed Web of Science ®Google Scholar
• Marschall HU, Wagner M, Zollner G, et al. (2005). Complementary stimulation of hepatobiliary transport and detoxification systems by rifampicin and ursodeoxycholic acid in humans. Gastroenterology 129:476–485.
   PubMed Web of Science ®Google Scholar
• Masica AL, Mayo G, Wilkinson GR. (2004). In vivo comparisons of constitutive cytochrome P450 3A activity assessed by alprazolam, triazolam, and midazolam. Clin Pharmacol Ther 76:341–349.
   PubMed Web of Science ®Google Scholar
• Miettinen TA. (1988). Cholesterol metabolism during ketoconazole treatment in man. J Lipid Res 29:43–51.
   PubMed Web of Science ®Google Scholar
• Mirghani RA, Sayi J, Aklillu E, et al. (2006). CYP3A5 genotype has significant effect on quinine 3-hydroxylation in Tanzanians, who have lower total CYP3A activity than a Swedish population. Pharmacogenet Genomics 16:637–645.
   PubMed Web of Science ®Google Scholar
• Morgan ET, Goralski KB, Piquette-Miller M, et al. (2008). Regulation of drug-metabolizing enzymes and transporters in infection, inflammation, and cancer. Drug Metab Dispos 36:205–216.
   PubMed Web of Science ®Google Scholar
• Ngaimisi E, Minzi O, Mugusi S, et al. (2014). Pharmacokinetic and pharmacogenomic modeling of the CYP3A activity marker 4beta-hydroxycholesterol during efavirenz treatment and efavirenz/rifampicin co-treatment. J Antimicrob Chemother 69:3311–3319.
   PubMed Web of Science ®Google Scholar
• Ngaimisi E, Mugusi S, Minzi O, et al. (2011). Effect of rifampicin and CYP2B6 genotype on long-term efavirenz autoinduction and plasma exposure in HIV patients with or without tuberculosis. Clin Pharm Ther 90:406–413.
   PubMed Web of Science ®Google Scholar
• Niemi M, Kivisto KT, Diczfalusy U, et al. (2006). Effect of SLCO1B1 polymorphism on induction of CYP3A4 by rifampicin. Pharmacogenet Genomics 16:565–568.
   PubMed Web of Science ®Google Scholar
• Ohnhaus EE, Breckenridge AM, Park BK. (1989). Urinary excretion of 6 beta-hydroxycortisol and the time course measurement of enzyme induction in man. Eur J Clin Pharmacol 36:39–46.
   PubMed Web of Science ®Google Scholar
• Ohno M, Yamaguchi I, Ito T, et al. (2000). Circadian variation of the urinary 6beta-hydroxycortisol to cortisol ratio that would reflect hepatic CYP3A activity. Eur J Clin Pharmacol 55:861–865.
   PubMed Web of Science ®Google Scholar
• Olkkonen VM, Beaslas O, Nissila E. (2012). Oxysterols and their cellular effectors. Biomolecules 2:76–103.
   PubMedGoogle Scholar
• Paine MF, Hart HL, Ludington SS, et al. (2006). The human intestinal cytochrome P450 “pie”. Drug Metab Dispos 34:880–886.
   PubMed Web of Science ®Google Scholar
• Saenger P. (1983). 6 beta-hydroxycortisol in random urine samples as an indicator of enzyme induction. Clin Pharmacol Ther 34:818–821.
   PubMed Web of Science ®Google Scholar
• Shin KH, Ahn LY, Choi MH, et al. (2016). Urinary 6beta-hydroxycortisol/cortisol ratio most highly correlates with midazolam clearance under hepatic CYP3A inhibition and induction in females: A pharmacometabolomics approach. Aaps J 18:1254–1261.
   PubMed Web of Science ®Google Scholar
• Shin KH, Choi MH, Lim KS, et al. (2013). Evaluation of endogenous metabolic markers of hepatic CYP3A activity using metabolic profiling and midazolam clearance. Clin Pharmacol Ther 94:601–609.
   PubMed Web of Science ®Google Scholar
• Simon JB. (1979). Studies on cholesterol ester formation and hydrolysis in liver disease: a selective review. Yale J Biol Med 52:117–126.
   PubMed Web of Science ®Google Scholar
• Soyinka JO, Onyeji CO, Omoruyi SI, et al. (2010). Pharmacokinetic interactions between ritonavir and quinine in healthy volunteers following concurrent administration. Br J Clin Pharmacol 69:262–270.
   PubMed Web of Science ®Google Scholar
• Suzuki Y, Itoh H, Fujioka T, et al. (2014). Association of plasma concentration of 4beta-hydroxycholesterol with CYP3A5 polymorphism and plasma concentration of indoxyl sulfate in stable kidney transplant recipients. Drug Metab Dispos 42:105–110.
   PubMed Web of Science ®Google Scholar
• Suzuki Y, Itoh H, Sato F, et al. (2013). Significant increase in plasma 4beta-hydroxycholesterol concentration in patients after kidney transplantation. J Lipid Res 54:2568–2572.
   PubMed Web of Science ®Google Scholar
• Szedlacsek SE, Wasowicz E, Hulea SA, et al. (1995). Esterification of oxysterols by human plasma lecithin-cholesterol acyltransferase. J Biol Chem 270:11812–11819.
   PubMed Web of Science ®Google Scholar
• Tomalik-Scharte D, Lutjohann D, Doroshyenko O, et al. (2009). Plasma 4beta-hydroxycholesterol: An endogenous CYP3A metric?. Clin Pharmacol Ther 86:147–153.
   PubMed Web of Science ®Google Scholar
• Twum-Barima Y, Carruthers SG. (1981). Quinidine-rifampin interaction. N Engl J Med 304:1466–1469.
   PubMed Web of Science ®Google Scholar
• Wanwimolruk S, Kang W, Coville PF, et al. (1995). Marked enhancement by rifampicin and lack of effect of isoniazid on the elimination of quinine in man. Br J Clin Pharmacol 40:87–91.
   PubMed Web of Science ®Google Scholar
• Wide K, Larsson H, Bertilsson L, Diczfalusy U. (2008). Time course of the increase in 4beta-hydroxycholesterol concentration during carbamazepine treatment of paediatric patients with epilepsy. Br J Clin Pharmacol 65:708–715.
   PubMed Web of Science ®Google Scholar
• Woolsey SJ, Mansell SE, Kim RB, et al. (2015). CYP3A activity and expression in nonalcoholic fatty liver disease. Drug Metab Dispos 43:1484–1490.
   PubMed Web of Science ®Google Scholar
• Wrighton SA, Brian WR, Sari MA, et al. (1990). Studies on the expression and metabolic capabilities of human liver cytochrome P450IIIA5 (HLp3). Mol Pharmacol 38:207–213.
   PubMed Web of Science ®Google Scholar
• Xue YJ, Hoffmann M, Tong Z, et al. (2016). Use of 4β-hydroxycholesterol in animal and human plasma samples as a biomarker for CYP3A induction. Bioanalysis. 8:215–228.
   PubMed Web of Science ®Google Scholar
• Yang J, Liao M, Shou M, et al. (2008). Cytochrome p450 turnover: Regulation of synthesis and degradation, methods for determining rates, and implications for the prediction of drug interactions. Curr Drug Metab 9:384–394.
   PubMed Web of Science ®Google Scholar
• Yang Z, Rodrigues AD. (2010). Does the long plasma half-life of 4beta-hydroxycholesterol impact its utility as a cytochrome P450 3A (CYP3A) metric?. J Clin Pharmacol 50:1330–1338.
   PubMed Web of Science ®Google Scholar
• Yeh RF, Gaver VE, Patterson KB, et al. (2006). Lopinavir/ritonavir induces the hepatic activity of cytochrome P450 enzymes CYP2C9, CYP2C19, and CYP1A2 but inhibits the hepatic and intestinal activity of CYP3A as measured by a phenotyping drug cocktail in healthy volunteers. J Acquir Immune Defic Syndr 42:52–60.
   PubMed Web of Science ®Google Scholar
• Yeung CK, Shen DD, Thummel KE, Himmelfarb J. (2014). Effects of chronic kidney disease and uremia on hepatic drug metabolism and transport. Kidney Int 85:522–528.
   PubMed Web of Science ®Google Scholar