cytochrome p 450 cyp3a

Summary

Summary: A cytochrome P-450 suptype that has specificity for a broad variety of lipophilic compounds, including STEROIDS; FATTY ACIDS; and XENOBIOTICS. This enzyme has clinical significance due to its ability to metabolize a diverse array of clinically important drugs such as CYCLOSPORINE; VERAPAMIL; and MIDAZOLAM. This enzyme also catalyzes the N-demethylation of ERYTHROMYCIN.

Top Publications

  1. Pondugula S, Dong H, Chen T. Phosphorylation and protein-protein interactions in PXR-mediated CYP3A repression. Expert Opin Drug Metab Toxicol. 2009;5:861-73 pubmed publisher
    ..During inflammation, NF-kappaB represses both PXR and CYP expression through protein-protein interactions with the PXR pathway. ..
  2. Press R, Ploeger B, Den Hartigh J, van der Straaten T, van Pelt J, Danhof M, et al. Explaining variability in tacrolimus pharmacokinetics to optimize early exposure in adult kidney transplant recipients. Ther Drug Monit. 2009;31:187-97 pubmed publisher
    ..5 times higher, fixed, starting dose compared with CYP3A5*3/*3 to reach the predefined target exposure early after transplantation. ..
  3. Li Y, Ross Viola J, Shay N, Moore D, Ricketts M. Human CYP3A4 and murine Cyp3A11 are regulated by equol and genistein via the pregnane X receptor in a species-specific manner. J Nutr. 2009;139:898-904 pubmed publisher
    ..Cyp3A11 mRNA was also induced in vivo in mice fed a soy protein-containing diet. The results presented herein demonstrate that there is a species-specific difference in the activation of PXR by isoflavones and equol. ..
  4. Pondugula S, Brimer Cline C, Wu J, Schuetz E, Tyagi R, Chen T. A phosphomimetic mutation at threonine-57 abolishes transactivation activity and alters nuclear localization pattern of human pregnane x receptor. Drug Metab Dispos. 2009;37:719-30 pubmed publisher
  5. Nishimura M, Narimatsu S, Naito S. Evaluation of induction potency of new drug candidates on CYP1A2 and CYP3A4 using real-time one-step RT-PCR in primary cultures of cryopreserved human hepatocytes. Drug Metab Pharmacokinet. 2009;24:446-50 pubmed
    ..A combination of real-time one-step RT-PCR and primary culture of cryopreserved human hepatocytes is suitable for evaluating of induction potency of a large number of new drug candidates. ..
  6. Ye X, Li W, Yan Y, Mao C, Cai R, Xu H, et al. Effects of cytochrome P4503A inducer dexamethasone on the metabolism and toxicity of triptolide in rat. Toxicol Lett. 2010;192:212-20 pubmed publisher
    ..This suggested that TP might decrease nephrotoxicity induced by DXM. These studies indicated that DXM had significant impact on the metabolism and the toxicity of TP as a therapeutic agent. ..
  7. Kawano D, Ueta J, Sankarankutty A, Pereira L, de Freitas O. Midazolam-related drug interactions: detection of risk situations to the patient safety in a brazilian teaching hospital. J Patient Saf. 2009;5:69-74 pubmed publisher
    ..Efforts directed toward monitoring interactions and preventing injuries from midazolam use are expected to have a substantial impact on patient safety concerning the use of midazolam. ..
  8. Sevior D, Hokkanen J, Tolonen A, Abass K, Tursas L, Pelkonen O, et al. Rapid screening of commercially available herbal products for the inhibition of major human hepatic cytochrome P450 enzymes using the N-in-one cocktail. Xenobiotica. 2010;40:245-54 pubmed publisher
  9. Paris B, Ogilvie B, Scheinkoenig J, Ndikum Moffor F, Gibson R, Parkinson A. In vitro inhibition and induction of human liver cytochrome p450 enzymes by milnacipran. Drug Metab Dispos. 2009;37:2045-54 pubmed publisher
    ..Given these results, milnacipran is not expected to cause clinically significant P450 inhibition or induction. ..

More Information

Publications62

  1. Punyawudho B, Cloyd J, Leppik I, Ramsay R, MARINO S, Pennell P, et al. Characterization of the time course of carbamazepine deinduction by an enzyme turnover model. Clin Pharmacokinet. 2009;48:313-20 pubmed publisher
    ..An enzyme turnover model adequately characterized the experimental data. Based on the predicted enzyme half-life from the final model, the deinduction process should be completed within 2 weeks after carbamazepine therapy is terminated. ..
  2. Macphee I. Use of pharmacogenetics to optimize immunosuppressive therapy. Ther Drug Monit. 2010;32:261-4 pubmed publisher
    ..As pharmacogenetic testing moves into routine clinical practice, standards for service delivery and reporting of results need to be established. ..
  3. Dong H, Lin W, Wu J, Chen T. Flavonoids activate pregnane x receptor-mediated CYP3A4 gene expression by inhibiting cyclin-dependent kinases in HepG2 liver carcinoma cells. BMC Biochem. 2010;11:23 pubmed publisher
    ..These results may have important implications on the pharmacokinetics of drugs co-administered with herbal remedy and herbal-drug interactions. ..
  4. Ballent M, Lifschitz A, Virkel G, Mate L, Lanusse C. Pretreatment with the inducers rifampicin and phenobarbital alters ivermectin gastrointestinal disposition. J Vet Pharmacol Ther. 2010;33:252-9 pubmed publisher
    ..An enhanced P-glycoprotein-mediated intestinal transport activity in pretreated animals (particularly in PBT pretreated rats) may explain the drastic changes observed on IVM disposition. ..
  5. Siemes C, Visser L, de Jong F, Coebergh J, Uitterlinden A, Hofman A, et al. Cytochrome P450 3A gene variation, steroid hormone serum levels and prostate cancer--The Rotterdam Study. Steroids. 2010;75:1024-32 pubmed publisher
    ..In line with this, no significant associations were observed for CYP3A genotypes and prostate cancer incidence. ..
  6. von Hentig N, Lotsch J. Cytochrome P450 3A inhibition by atazanavir and ritonavir, but not demography or drug formulation, influences saquinavir population pharmacokinetics in human immunodeficiency virus type 1-infected adults. Antimicrob Agents Chemother. 2009;53:3524-7 pubmed publisher
    ..In contrast, age, sex, weight, pregnancy, and the pharmaceutical formulation exerted only minor, nonsignificant effects. ..
  7. Samer C, Daali Y, Wagner M, Hopfgartner G, Eap C, Rebsamen M, et al. The effects of CYP2D6 and CYP3A activities on the pharmacokinetics of immediate release oxycodone. Br J Pharmacol. 2010;160:907-18 pubmed publisher
    ..Shunting to CYP2D6 pathway was observed after CYP3A4 inhibition. Drug-drug interactions via CYP2D6 and CYP3A affected oxycodone pharmacokinetics and its magnitude depended on CYP2D6 genotype. ..
  8. Killer N, Hock M, Gehlhaus M, Capetian P, Knoth R, Pantazis G, et al. Modulation of androgen and estrogen receptor expression by antiepileptic drugs and steroids in hippocampus of patients with temporal lobe epilepsy. Epilepsia. 2009;50:1875-90 pubmed publisher
    ..The HN25.1 cell line holds promise to investigate the correlation between drug application and AR regulation, and to specifically address issues that are relevant to human TLE patients. ..
  9. Fortún Abete J. [Micafungin for therapy of invasive candidiasis in solid organ transplant recipients]. Rev Iberoam Micol. 2009;26:65-8 pubmed publisher
    ..The clinical results, its safety profile and the low grade of medical interactions permit micafungin to be considered for therapy in specific groups of transplant patients. ..
  10. Moore C, Shahrokh K, Sontum S, Cheatham T, Yost G. Improved cytochrome P450 3A4 molecular models accurately predict the Phe215 requirement for raloxifene dehydrogenation selectivity. Biochemistry. 2010;49:9011-9 pubmed publisher
    ..Thus, the improved structural model predicted novel enzyme-substrate interactions that control the selective dehydrogenation of raloxifene to its protein-binding intermediate. ..
  11. Kirby L, Johnson B, Adams L, Eberwein D, Zhang K, Murray S, et al. Effect of casopitant, a novel NK-1 receptor antagonist, on the pharmacokinetics and pharmacodynamics of steady-state warfarin. J Clin Pharmacol. 2010;50:566-75 pubmed publisher
    ..31-fold (90% confidence interval [CI]: 1.22, 1.41), and S-warfarin AUC was increased 1.27-fold (90% CI: 1.18, 1.38) on day 14 in regimen B. Steady-state INR values were not affected by either casopitant regimen. ..
  12. Yardley D. Proactive management of adverse events maintains the clinical benefit of ixabepilone. Oncologist. 2009;14:448-55 pubmed publisher
    ..By effectively managing adverse events and taking steps to minimize them, clinicians can ensure that patients derive the maximum benefit from ixabepilone therapy. ..
  13. Croyle M. Long-term virus-induced alterations of CYP3A-mediated drug metabolism: a look at the virology, immunology and molecular biology of a multi-faceted problem. Expert Opin Drug Metab Toxicol. 2009;5:1189-211 pubmed publisher
  14. Isla Tejera B, Aumente Rubio M, Martinez Moreno J, Reyes Malia M, Arizon J, Suárez García A. [Pharmacogenetic analysis of the absorption kinetics of cyclosporine in a population of Spanish cardiac transplant patients]. Farm Hosp. 2009;33:324-9 pubmed
    ..Our results show that genotype differences in MDR1 3435C > T can explain part of the variability in cyclosporine absorption among individuals in the population of Spanish cardiac transplant recipients. ..
  15. Sugatani J, Osabe M, Kurosawa M, Kitamura N, Ikari A, Miwa M. Induction of UGT1A1 and CYP2B6 by an antimitogenic factor in HepG2 cells is mediated through suppression of cyclin-dependent kinase 2 activity: cell cycle-dependent expression. Drug Metab Dispos. 2010;38:177-86 pubmed publisher
  16. Yanni S, Annaert P, Augustijns P, Ibrahim J, Benjamin D, Thakker D. In vitro hepatic metabolism explains higher clearance of voriconazole in children versus adults: role of CYP2C19 and flavin-containing monooxygenase 3. Drug Metab Dispos. 2010;38:25-31 pubmed publisher
    ..Although expression of CYP2C19 and FMO3 is not significantly different in children versus adults, these enzymes seem to contribute to higher metabolic clearance of voriconazole in children versus adults. ..
  17. Hostler D, Zhou J, Tortorici M, Bies R, Rittenberger J, Empey P, et al. Mild hypothermia alters midazolam pharmacokinetics in normal healthy volunteers. Drug Metab Dispos. 2010;38:781-8 pubmed publisher
    ..Future studies in patients who receive lower levels and a longer duration of hypothermia are warranted. ..
  18. Lamba V, Panetta J, Strom S, Schuetz E. Genetic predictors of interindividual variability in hepatic CYP3A4 expression. J Pharmacol Exp Ther. 2010;332:1088-99 pubmed publisher
    ..This approach identified sex and polymorphisms in FoxA2, HNF4alpha, FoxA3, PXR, ABCB1, and the CYP3A4 promoter that together explained as much as 24.6% of the variation in hepatic CYP3A4 expression. ..
  19. Oliver P, Lubomirov R, Carcas A. Genetic polymorphisms of CYP1A2, CYP3A4, CYP3A5, pregnane/steroid X receptor and constitutive androstane receptor in 207 healthy Spanish volunteers. Clin Chem Lab Med. 2010;48:635-9 pubmed publisher
  20. Fang Z, Zhang Y, Ge G, Huo H, Liang S, Yang L. Time-dependent inhibition (TDI) of CYP3A4 and CYP2C9 by noscapine potentially explains clinical noscapine-warfarin interaction. Br J Clin Pharmacol. 2010;69:193-9 pubmed publisher
    ..9% and 48.9% using C(max) or 41.8% and 32.7% using unbound C(max) with TDI prediction equation. TDI of CYP3A4 and CYP2C9 by noscapine potentially explains clinical noscapine-warfarin interaction. ..
  21. Yokooji T, Kida M, Mori M, Akashi H, Mori N, Yoshihara S, et al. Interaction of Rhei Rhizoma extract with cytochrome P450 3A and efflux transporters in rats. Pharmazie. 2010;65:367-74 pubmed
  22. Kim D, Cho K, Oh W, Lee C, Lee S, Jung J, et al. EaMEAD: Activation energy prediction of cytochrome P450 mediated metabolism with effective atomic descriptors. J Chem Inf Model. 2009;49:1643-54 pubmed publisher
    ..The reliability and ease of use of this model will greatly facilitate early stage PK predictions and rational drug design. Moreover, the model can be applied to develop the Ea prediction model of various types of chemical reactions. ..
  23. Ho Y, Huang D, Hsueh W, Lai M, Yu H, Tsai T. Effects of St. John's wort extract on indinavir pharmacokinetics in rats: differentiation of intestinal and hepatic impacts. Life Sci. 2009;85:296-302 pubmed publisher
    ..The application of the animal model to investigating herb-drug interactions or other relevant research purposes is envisioned. ..
  24. Madgula V, Avula B, Pawar R, Shukla Y, Khan I, Walker L, et al. Characterization of in vitro pharmacokinetic properties of hoodigogenin A from Hoodia gordonii. Planta Med. 2010;76:62-9 pubmed publisher
    ..The compound strongly inhibited CYP3A4 activity (IC(50) 3 microM), indicating a possibility of drug-herb/botanical interactions when products containing H. gordonii are used simultaneously with other botanicals/herbs/drugs. ..
  25. Kedem E, Shahar E, Hassoun G, Pollack S. Iatrogenic Cushing's syndrome due to coadministration of ritonavir and inhaled budesonide in an asthmatic human immunodeficiency virus infected patient. J Asthma. 2010;47:830-1 pubmed publisher
    ..In patients treated with inhaled or intranasal corticosteroids together with cART there may be a higher incidence of iatrogenic CS. CS should be looked for, and management considered carefully. ..
  26. Ganesan S, Sahu R, Walker L, Tekwani B. Cytochrome P450-dependent toxicity of dapsone in human erythrocytes. J Appl Toxicol. 2010;30:271-5 pubmed publisher
    ..The results provide useful insights into CYP-dependent hemotoxicity of dapsone in human erythrocytes. ..
  27. Zhang X, Galinsky R, Kimura R, Quinney S, Jones D, Hall S. Inhibition of CYP3A by erythromycin: in vitro-in vivo correlation in rats. Drug Metab Dispos. 2010;38:61-72 pubmed publisher
    ..1-fold for the in vitro-estimated CYP3A activity and the in vivo CL(int), respectively. This study demonstrates that in vivo DDIs are predictable from in vitro data when the appropriate model and parameter estimates are available. ..
  28. Pérez V, Sánchez Parra C, Serrano Villar S. [Etravirine drug interactions]. Enferm Infecc Microbiol Clin. 2009;27 Suppl 2:27-31 pubmed publisher
    ..Interaction with fosamprenavir/ritonavir is not clinically significant, although their plasma levels vary slightly when used in combination with ETR. ETR shows no interactions with darunavir/ritonavir...
  29. Anderson P, Aquilante C, Gardner E, Predhomme J, McDaneld P, Bushman L, et al. Atazanavir pharmacokinetics in genetically determined CYP3A5 expressors versus non-expressors. J Antimicrob Chemother. 2009;64:1071-9 pubmed publisher
    ..Thus, CYP3A5, ABCB1 and UGT1A1 polymorphisms are associated with atazanavir pharmacokinetics and pharmacodynamics in vivo. ..
  30. Spangler M, Saxena S. Warfarin and bosentan interaction in a patient with pulmonary hypertension secondary to bilateral pulmonary emboli. Clin Ther. 2010;32:53-6 pubmed publisher
    ..We describe here a probable drug interaction between bosentan and warfarin that resulted in a 43% increase in warfarin dose to maintain the patient's therapeutic INR. ..
  31. Perdaems N, Blasco H, Vinson C, Chenel M, Whalley S, Cazade F, et al. Predictions of metabolic drug-drug interactions using physiologically based modelling: Two cytochrome P450 3A4 substrates coadministered with ketoconazole or verapamil. Clin Pharmacokinet. 2010;49:239-58 pubmed publisher
  32. Takahashi N, Inui N, Morita H, Takeuchi K, Uchida S, Watanabe H, et al. Effect of thyroid hormone on the activity of CYP3A enzyme in humans. J Clin Pharmacol. 2010;50:88-93 pubmed publisher
    ..92 to 5.88 (P < .05). These results strongly suggested that thyroid hormone reduced CYP3A activity in human and may influence the pharmacokinetics of concomitant CYP3A substrate drugs. ..
  33. Chen J, Tran C, Xiao L, Palamanda J, Klapmuts T, Kumari P, et al. Co-induction of CYP3A12 and 3A26 in dog liver slices by xenobiotics: species difference between human and dog CYP3A induction. Drug Metab Lett. 2009;3:61-6 pubmed
    ..This finding suggests that these two amino acids may play a role in the binding specificity of ligands. ..
  34. Yue J, Peng R. Does CYP2E1 play a major role in the aggravation of isoniazid toxicity by rifampicin in human hepatocytes?. Br J Pharmacol. 2009;157:331-3 pubmed publisher
    ..The study by Shen et al. suggests that another drug-metabolizing enzyme rather than CYP2E1 could be involved in the aggravation of isoniazid toxicity by rifampicin in human hepatocytes. ..
  35. Moore C, Reilly C, Yost G. CYP3A4-Mediated oxygenation versus dehydrogenation of raloxifene. Biochemistry. 2010;49:4466-75 pubmed publisher
    ..These findings not only confirm CYP3A4-mediated dehydrogenation of raloxifene to a reactive diquinone methide but also suggest a novel route of raloxifene toxicity. ..
  36. Larriba J, Imperiali N, Groppa R, Giordani C, Algranatti S, Redal M. Pharmacogenetics of immunosuppressant polymorphism of CYP3A5 in renal transplant recipients. Transplant Proc. 2010;42:257-9 pubmed publisher
    ..The genetic polymorphisms can determine responses to drugs. The molecular diagnosis must be transferred to clinical practice so as to guide selection of medicine and drug doses to be optimal for each individual. ..
  37. Dapkunas J, Sazonovas A, Japertas P. Probabilistic prediction of the human CYP3A4 and CYP2D6 metabolism sites. Chem Biodivers. 2009;6:2101-6 pubmed publisher
    ..The results obtained so far show promising perspectives for the utilization of the GALAS modeling in the analysis of regioselectivity for other important biotransformation enzymes--a work currently in progress. ..
  38. Asaoka Y, Sakai H, Sasaki J, Goryo M, Yanai T, Masegi T, et al. Changes in the gene expression and enzyme activity of hepatic cytochrome P450 in juvenile Sprague-Dawley rats. J Vet Med Sci. 2010;72:471-9 pubmed
    ..Thus, our results on developmental difference of hepatic CYPs in juvenile rats are useful to identify underlying age-dependent susceptibility of chemical-induced toxicity, and to understand developmental change of chemical disposition. ..
  39. Franke R, Carducci M, Rudek M, Baker S, Sparreboom A. Castration-dependent pharmacokinetics of docetaxel in patients with prostate cancer. J Clin Oncol. 2010;28:4562-7 pubmed publisher
    ..It is recommended that castration- and/or hormone-related changes in the clearance of oncology drugs should be considered as a possible risk factor for treatment failure. ..
  40. Hyland R, Osborne T, Payne A, Kempshall S, Logan Y, Ezzeddine K, et al. In vitro and in vivo glucuronidation of midazolam in humans. Br J Clin Pharmacol. 2009;67:445-54 pubmed publisher
    ..Direct N-glucuronidation of MDZ occurs in vivo. Pharmacokinetic modelling using Simcyp illustrates an increased role for UGT1A4 under CYP3A inhibited conditions. ..
  41. Xin H, Wu X, Li Q, Yu A, Xiong L. Effects of Schisandra sphenanthera extract on the pharmacokinetics of midazolam in healthy volunteers. Br J Clin Pharmacol. 2009;67:541-6 pubmed publisher
    ..SchE can markedly increase the oral bioavailability of midazolam in healthy volunteers. SchE is an inhibitor of CYP3A and has a high susceptibility to alter the disposition of drugs metabolized by CYP3A. ..
  42. Nishimura M, Koeda A, Morikawa H, Satoh T, Narimatsu S, Naito S. Tissue-specific mRNA expression profiles of drug-metabolizing enzymes and transporters in the cynomolgus monkey. Drug Metab Pharmacokinet. 2009;24:139-44 pubmed
  43. Allmyr M, Panagiotidis G, Sparve E, Diczfalusy U, Sandborgh Englund G. Human exposure to triclosan via toothpaste does not change CYP3A4 activity or plasma concentrations of thyroid hormones. Basic Clin Pharmacol Toxicol. 2009;105:339-44 pubmed publisher
    ..This indicates that the normal use of triclosan-containing toothpaste is not likely to alter metabolism of drugs via CYP3A4 induction or cause adverse events because of thyroid disturbances in humans. ..
  44. Murai K, Yamazaki H, Nakagawa K, Kawai R, Kamataki T. Deactivation of anti-cancer drug letrozole to a carbinol metabolite by polymorphic cytochrome P450 2A6 in human liver microsomes. Xenobiotica. 2009;39:795-802 pubmed publisher
    ..Polymorphic variation of CYP2A6 is considered to be relevant to inter-subject variation in therapeutic exposure of letrozole. ..
  45. Lutz U, Bittner N, Ufer M, Lutz W. Quantification of cortisol and 6 beta-hydroxycortisol in human urine by LC-MS/MS, and gender-specific evaluation of the metabolic ratio as biomarker of CYP3A activity. J Chromatogr B Analyt Technol Biomed Life Sci. 2010;878:97-101 pubmed publisher
    ..This non-invasive biomarker for CYP3A activity lends itself for the study of genetic differences as well as enzyme induction or inhibition in the clinical setting without the need of using a probe drug. ..
  46. Abdou R, Sasaki K, Khalil W, Shah S, Murasawa Y, Shimoda M. Effects of several pyrethroids on hepatic cytochrome P450 activities in rats. J Vet Med Sci. 2010;72:425-33 pubmed
    ..As permethrin and fenpropathrin were potent inhibitor for CYP1A, they may result in substantial accumulation of some chemicals. The resultant accumulation may lead to fatal toxicities in some case. ..
  47. Hum M, McLaughlin B, Roman G, Vlahakis J, Szarek W, Nakatsu K. The effects of azole-based heme oxygenase inhibitors on rat cytochromes P450 2E1 and 3A1/2 and human cytochromes P450 3A4 and 2D6. J Pharmacol Exp Ther. 2010;334:981-7 pubmed publisher
    ..Four structural regions of QC-xx were analyzed, leading to the identification of structures that confer a decreased effect on both rat and human P450 isoforms studied while maintaining an inhibitory effect on the HOs...
  48. Johnson B, Adams L, Zhang K, Gainer S, Kirby L, Blum R, et al. Ketoconazole and rifampin significantly affect the pharmacokinetics, but not the safety or QTc interval, of casopitant, a neurokinin-1 receptor antagonist. J Clin Pharmacol. 2010;50:951-9 pubmed publisher
  49. Istrate M, Nussler A, Eichelbaum M, Burk O. Regulation of CYP3A4 by pregnane X receptor: The role of nuclear receptors competing for response element binding. Biochem Biophys Res Commun. 2010;393:688-93 pubmed publisher
    ..In summary, our results demonstrate that nuclear receptor binding to PXR response elements interferes with PXR-mediated expression and induction of CYP3A4 and thereby contributes to the interindividual variability of induction. ..
  50. Kuypers D, Naesens M, de Jonge H, Lerut E, Verbeke K, Vanrenterghem Y. Tacrolimus dose requirements and CYP3A5 genotype and the development of calcineurin inhibitor-associated nephrotoxicity in renal allograft recipients. Ther Drug Monit. 2010;32:394-404 pubmed publisher
  51. Hesselink D, Bouamar R, van Gelder T. The pharmacogenetics of calcineurin inhibitor-related nephrotoxicity. Ther Drug Monit. 2010;32:387-93 pubmed publisher
    ..In this paper this evidence is reviewed, with special emphasis on the role of genetic factors influencing metabolism and transportation of CNIs in both acceptor and donor. ..
  52. Pithavala Y, Tortorici M, Toh M, Garrett M, Hee B, Kuruganti U, et al. Effect of rifampin on the pharmacokinetics of Axitinib (AG-013736) in Japanese and Caucasian healthy volunteers. Cancer Chemother Pharmacol. 2010;65:563-70 pubmed publisher
    ..The results support a common axitinib starting dose in both populations. Potent inducers of drug-metabolizing enzymes reduce axitinib exposure and dose adjustments may be needed for optimal efficacy. ..
  53. Benet L. A Holy Grail of clinical pharmacology: prediction of drug pharmacokinetics and pharmacodynamics in the individual patient. Clin Pharmacol Ther. 2009;86:133-4 pubmed publisher
    ..However, one should not expect any prediction success for drugs primarily metabolized by the major cytochrome P450 enzyme, CYP3A4, whether one uses an exogenous drug or an endogenous metabolic process, such as the oxidation of cortisol. ..