61: Tiainen S-M, Heinonen H, Koskinen A, Mäkelä S, Laitio R, Löyttyniemi E, Mäkelä K, Saari TI, Uusalo P. Premedication with intranasal dexmedetomidine in patients undergoing total knee arthroplasty (TKADEX) – a prospective, double-blinded, randomised controlled trial. BJA Open, accepted, BJAO-D-24-00073
60: Ashraf MW, Poikola S, Neuvonen M, Kiiski JI, Kontinen VK, Olkkola KT, Backman JT, Niemi M, Saari TI. Population Pharmacokinetic Quantification of CYP2D6 Activity in Codeine Metabolism in Ambulatory Surgical Patients for Model-Informed Precision Dosing. Clin Pharmacokinet. 2024 Nov;63(11):1547-1560. doi: 10.1007/s40262-024-01433-9. Epub 2024 Oct 23. PMID: 39441506.
59: Tiainen SM, Anderson BJ, Rinne E, Tornio A, Engström MT, Saari TI, Uusalo P. Absorption pharmacokinetics and feasibility of intranasal dexmedetomidine in patients under general anaesthesia. Acta Anaesthesiol Scand. 2024 Oct;68(9):1182-1191. doi: 10.1111/aas.14473. Epub 2024 Jun 19. PMID: 38895976.
58: Saari TI, Strang J, Dale O. Clinical Pharmacokinetics and Pharmacodynamics of Naloxone. Clin Pharmacokinet. 2024 Apr;63(4):397-422. doi: 10.1007/s40262-024-01355-6. Epub 2024 Mar 14. PMID: 38485851
57: Laaksonen M, Rinne J, Rahi M, Posti JP, Laitio R, Kivelev J, Saarenpää I, Laukka D, Frösen J, Ronkainen A, Bendel S, Långsjö J, Ala-Peijari M, Saunavaara J, Parkkola R, Nyman M, Martikainen IK, Dickens AM, Rinne J, Valtonen M, Saari TI, Koivisto T, Bendel P, Roine T, Saraste A, Vahlberg T, Tanttari J, Laitio T. Effect of xenon on brain injury, neurological outcome, and survival in patients after aneurysmal subarachnoid hemorrhage-study protocol for a randomized clinical trial. Trials. 2023 Jun 19;24(1):417. doi: 10.1186/s13063-023-07432-8. PMID: 37337295.
56: Brinck ECV, Virtanen T, Mäkelä S, Soini V, Hynninen V-V, Mulo J, Savolainen U, Rantakokko J, Maisniemi K, Liukas A, Olkkola KT, Kontinen V, Tarkkila P, Peltoniemi M, Saari TI. S-ketamine in patient-controlled analgesia with oxycodone improves analgesia in a dose-dependent manner after major lumbar fusion surgery: a randomized, double-blind, placebo-controlled clinical trial. PLoS One. 2021 Jun 7;16(6):e0252626. doi: 10.1371/journal.pone.0252626 . eCollection 2021. PMID: 34097713. Preprint published in medRxiv 2021.01.22.21250352;
55: Sisa K, Huoponen S, Ettala O, Antila H, Saari TI, Uusalo P. Effects of pre-emptive pregabalin and multimodal anesthesia on postoperative opioid requirements in patients undergoing robot-assisted laparoscopic prostatectomy. BMC Urol. 2021 Feb 2;21(1):14. doi: 10.1186/s12894-021-00785-9. PMID: 33530959
54: Fihlman M, Karru E, Varpe P, Huhtinen H, Hagelberg N, Saari TI, Olkkola KT. Feasibility of a transmucosal sublingual fentanyl tablet as a procedural pain treatment in colonoscopy patients: a prospective placebo-controlled randomized study. Sci Rep. 2020 Dec 1;10(1):20897. doi: 10.1038/s41598-020-78002-0. PMID: 33262414
53: Seppänen S-M, Kuuskoski R, Mäkelä K, Saari TI, Uusalo P. Intranasal dexmedetomidine reduces postoperative opioid requirement in patients undergoing total knee arthroplasty under general anesthesia. J Arthroplasty. 2021 Feb 16;36(3):978-985.e1, 2021. doi.org/10.1016/j.arth.2020.09.032. PMID: 33046329
52: Havrdová M, Saari TI, Jalonen J, Peltoniemi M, Kurkela M, Vahlberg T, Tienhaara A, Backman JT, Olkkola KT, Schramko A. Relationship of Edoxaban Plasma Concentration and Blood Coagulation in Healthy Volunteers Using Standard Laboratory Tests and Viscoelastic Analysis. J Clin Pharmacol. 2020 Oct 7. doi: 10.1002/jcph.1758. Online ahead of print. PMID: 33027547.
51: Kamp J, Olofsen E, Henthorn T, van Velzen M, Niesters M, Dahan A, Backman JT, Drover DR, Elkomy MH, Fanta S, Flint RB, Gustafsson LL, Hammer GB, Herd DW, Kalso E, Mathot RAA, Olkkola K, Peltoniemi M, Persson J, Ramamoorthy C, Saari TI, Sherwin C. Pharmacokinetics of the NMDA receptor antagonist ketamine: a systematic review of the literature and meta-analysis. Anesthesiology. 2020 Dec 1;133(6):1192-1213. doi.org/10.1097/ALN.0000000000003577 PMID: 32997732.
50: Ashraf M, Uusalo P, Scheinin M, Saari TI. Population modelling of dexmedetomidine pharmacokinetics and hemodynamic effects after intravenous and subcutaneous administration, Clin Pharmacokin. 2020 Nov;59(11):1467-1482. doi.org/10.1007/s40262-020-00900-3. PMID: 32462542
49: Kallioinen M, Posti JP, Rahi M, Sharma D, Katila A, Grönlund J, Vahlberg T, Frantzen J, Olkkola K, Saari TI, Takala R. Cerebral autoregulation after aneyrysmal subarachnoid haemorrhage. A preliminary study comparing dexmedetomidine to Propofol and midazolam. Acta Anaesthesiol Scand. 2020 Sep 7 64:1278-1286. doi-org.ezproxy.utu.fi/10.1111/aas.13663 PMID: 32609878
48: Li X, Frechen S, Moj D, Lehr T, Taubert M, Hsin C-H, Mikus G, Neuvonen PJ, Olkkola KT, Saari TI, Fuhr U. A Physiologically-Based Pharmacokinetic Model of Voriconazole Integrating Time-Dependent Inhibition, Genetic Polymorphisms of CYP2C19 and Predictions of Drug-Drug Interactions. Clin Pharmacokinet. 2020 Jun;59(6):781-808 doi.org/10.1007/s40262-019-00856-z PMID: 31853755
47: Uusalo P, Guillaume S, Siren S, Manner T, Vilo S, Scheinin M, Saari TI. Pharmacokinetics and Sedative Effects of Intranasal Dexmedetomidine in Ambulatory Pediatric Patients. Anesth Analg. 2020 Apr;130(4):949-957. doi:10.1213/ANE.0000000000004264. PMID: 31206433
46: Uusalo P, Lehtinen M, Löyttyniemi E, Manner T, Scheinin M, Saari TI. Premedication with intranasal dexmedetomidine decreases barbiturate requirement in pediatric patients sedated for magnetic resonance imaging: a retrospective study. BMC Anesthesiol. 2019 Feb 13;19(1):22. doi: 10.1186/s12871-019-0690-1. PubMed PMID: 30760215.
45: Uusalo P, Jätinvuori H, Löyttyniemi E, Kosola J, Saari TI. Intranasal Low-Dose Dexmedetomidine Reduces Postoperative Opioid Requirement in Patients Undergoing Hip Arthroplasty Under General Anesthesia. J Arthroplasty. 2019 Jan 7. pii: S0883-5403(18)31238-5. doi: 10.1016/j.arth.2018.12.036. PubMed PMID: 30733071.
44: Ahtiala M, Soppi E, Saari TI. Sequential Organ Failure Assessment (SOFA) to Predict Pressure Ulcer Risk in Intensive Care Patients: A Retrospective Cohort Study. Ostomy Wound Manage. 2018 Oct;64(10):32-38. PubMed PMID: 30312156.
43: Fihlman M, Hemmilä T, Hagelberg NM, Backman JT, Laitila J, Laine K, Neuvonen PJ, Olkkola KT, Saari TI. Voriconazole greatly increases the exposure to oral buprenorphine. Eur J Clin Pharmacol. 2018 Dec;74(12):1615-1622. doi: 10.1007/s00228-018-2548-8. Epub 2018 Aug 30. PubMed PMID: 30167757.
42: Ashraf MW, Peltoniemi MA, Olkkola KT, Neuvonen PJ, Saari TI. Semimechanistic Population Pharmacokinetic Model to Predict the Drug-Drug Interaction Between S-ketamine and Ticlopidine in Healthy Human Volunteers. CPT Pharmacometrics Syst Pharmacol. 2018 Oct;7(10):687-697. doi: 10.1002/psp4.12346. Epub 2018 Sep 10. PubMed PMID: 30091858; PubMed Central PMCID: PMC6202471.
41: Uusalo P, Al-Ramahi D, Tilli I, Aantaa RA, Scheinin M, Saari TI. Subcutaneously administered dexmedetomidine is efficiently absorbed and is associated with attenuated cardiovascular effects in healthy volunteers. Eur J Clin Pharmacol. 2018 Aug;74(8):1047-1054. doi: 10.1007/s00228-018-2461-1. Epub 2018 Apr 17. PubMed PMID: 29666901.
40: Hagelberg NM, Fihlman M, Hemmilä T, Backman JT, Laitila J, Neuvonen PJ, Laine K, Olkkola KT, Saari TI. Rifampicin decreases exposure to sublingual buprenorphine in healthy subjects. Pharmacol Res Perspect. 2016 Nov 3;4(6):e00271. doi: 10.1002/prp2.271. eCollection 2016 Dec. PubMed PMID: 28097004; PubMed Central PMCID: PMC5226287.
39: Fihlman M, Hemmilä T, Hagelberg NM, Kuusniemi K, Backman JT, Laitila J, Laine K, Neuvonen PJ, Olkkola KT, Saari TI. Voriconazole more likely than posaconazole increases plasma exposure to sublingual buprenorphine causing a risk of a clinically important interaction. Eur J Clin Pharmacol. 2016 Nov;72(11):1363-1371. Epub 2016 Aug 10. PubMed PMID: 27510521.
38: Peltoniemi MA, Hagelberg NM, Olkkola KT, Saari TI. Ketamine: A Review of Clinical Pharmacokinetics and Pharmacodynamics in Anesthesia and Pain Therapy. Clin Pharmacokinet. 2016 Sep;55(9):1059-77. doi: 10.1007/s40262-016-0383-6. Review. PubMed PMID: 27028535.
37: Jeleazcov C, Ihmsen H, Saari TI, Rohde D, Mell J, Fröhlich K, Krajinovic L, Fechner J, Schwilden H, Schüttler J. Patient-controlled Analgesia with Target-controlled Infusion of Hydromorphone in Postoperative Pain Therapy. Anesthesiology. 2016 Jan;124(1):56-68. doi: 10.1097/ALN.0000000000000937. PubMed PMID: 26556729.
36: Saarikoski T, Saari TI, Hagelberg NM, Backman JT, Neuvonen PJ, Scheinin M, Olkkola KT, Laine K. Effects of terbinafine and itraconazole on the pharmacokinetics of orally administered tramadol. Eur J Clin Pharmacol. 2015 Mar;71(3):321-7. doi: 10.1007/s00228-014-1799-2. Epub 2015 Jan 6. PubMed PMID: 25560051.
35: Saari TI, Ihmsen H, Mell J, Fröhlich K, Fechner J, Schüttler J, Jeleazcov C. Influence of intensive care treatment on the protein binding of sufentanil and hydromorphone during pain therapy in postoperative cardiac surgery patients. Br J Anaesth. 2014 Oct;113(4):677-87. doi: 10.1093/bja/aeu160. Epub 2014 Jul 6. PubMed PMID: 25001621.
34: Jeleazcov C, Saari TI, Ihmsen H, Mell J, Fröhlich K, Krajinovic L, Fechner J, Schüttler J. Population pharmacokinetic modeling of hydromorphone in cardiac surgery patients during postoperative pain therapy. Anesthesiology. 2014 Feb;120(2):378-91. doi: 10.1097/ALN.0b013e3182a76d05. PubMed PMID: 23958818.
33: Frechen S, Junge L, Saari TI, Suleiman AA, Rokitta D, Neuvonen PJ, Olkkola KT, Fuhr U. A semiphysiological population pharmacokinetic model for dynamic inhibition of liver and gut wall cytochrome P450 3A by voriconazole. Clin Pharmacokinet. 2013 Sep;52(9):763-81. doi: 10.1007/s40262-013-0070-9. PubMed PMID: 23653047.
32: Olkkola KT, Kontinen VK, Saari TI, Kalso EA. Does the pharmacology of oxycodone justify its increasing use as an analgesic? Trends Pharmacol Sci. 2013 Apr;34(4):206-14. doi: 10.1016/j.tips.2013.02.001. Epub 2013 Mar 4. Review. PubMed PMID: 23465410.
31: Saarikoski T, Saari TI, Hagelberg NM, Neuvonen M, Neuvonen PJ, Scheinin M, Olkkola KT, Laine K. Rifampicin markedly decreases the exposure to oral and intravenous tramadol. Eur J Clin Pharmacol. 2013 Jun;69(6):1293-301. doi: 10.1007/s00228-012-1460-x. Epub 2012 Dec 15. PubMed PMID: 23242004.
30: Ihmsen H, Saari TI. [Dexmedetomidine. Pharmacokinetics and pharmacodynamics]. Anaesthesist. 2012 Dec;61(12):1059-66. doi: 10.1007/s00101-012-2114-1. Review. German. PubMed PMID: 23223843.
29: Hagelberg NM, Saarikoski T, Saari TI, Neuvonen M, Neuvonen PJ, Turpeinen M, Scheinin M, Laine K, Olkkola KT. Ticlopidine inhibits both O-demethylation and renal clearance of tramadol, increasing the exposure to it, but itraconazole has no marked effect on the ticlopidine-tramadol interaction. Eur J Clin Pharmacol. 2013 Apr;69(4):867-75. doi: 10.1007/s00228-012-1433-0. Epub 2012 Oct 26. PubMed PMID: 23099620.
28: Saari TI, Fechner J, Ihmsen H, Schüttler J, Jeleazcov C. Analysis of total and unbound hydromorphone in human plasma by ultrafiltration and LC MS/MS: application to clinical trial in patients undergoing open heart surgery. J Pharm Biomed Anal. 2012 Dec;71:63-70. doi: 10.1016/j.jpba.2012.07.025. Epub 2012 Jul 31. PubMed PMID: 22884788.
27: Jeleazcov C, Saari TI, Ihmsen H, Schüttler J, Fechner J. Changes in total and unbound concentrations of sufentanil during target controlled infusion for cardiac surgery with cardiopulmonary bypass. Br J Anaesth. 2012 Nov;109(5):698-706. doi: 10.1093/bja/aes253. Epub 2012 Jul 24. PubMed PMID: 22831891.
26: Peltoniemi MA, Saari TI, Hagelberg NM, Laine K, Kurkinen KJ, Neuvonen PJ, Olkkola KT. Rifampicin has a profound effect on the pharmacokinetics of oral S-ketamine and less on intravenous S-ketamine. Basic Clin Pharmacol Toxicol. 2012 Nov;111(5):325-32. doi: 10.1111/j.1742-7843.2012.00908.x. Epub 2012 Jun 27. PubMed PMID: 22676424.
25: Saari TI, Fechner J, Ihmsen H, Schüttler J, Jeleazcov C. Determination of total and unbound sufentanil in human plasma by ultrafiltration and LC MS/MS: application to clinical pharmacokinetic study. J Pharm Biomed Anal. 2012 Jul;66:306-13. doi: 10.1016/j.jpba.2012.03.050. Epub 2012 Apr 3. PubMed PMID: 22522038.
24: Peltoniemi MA, Saari TI, Hagelberg NM, Laine K, Neuvonen PJ, Olkkola KT. S-ketamine concentrations are greatly increased by grapefruit juice. Eur J Clin Pharmacol. 2012 Jun;68(6):979-86. doi: 10.1007/s00228-012-1214-9. PubMed PMID: 22286159.
23: Nieminen TH, Hagelberg NM, Saari TI, Grönlund J, Neuvonen PJ, Olkkola KT. Re: Pergolizzi et al. 2011: Exposure to potential CYP450 pharmacokinetic drug-drug interactions. Pain Pract. 2012 Jan;12(1):81-2. doi: 10.1111/j.1533-2500.2011.00506.x. PubMed PMID: 22230379.
22: Saari TI, Ihmsen H, Neuvonen PJ, Olkkola KT, Schwilden H. Oxycodone clearance is markedly reduced with advancing age: a population pharmacokinetic study. Br J Anaesth. 2012 Mar;108(3):491-8. doi: 10.1093/bja/aer395. Epub 2011 Dec 26. PubMed PMID: 22201184.
21: Peltoniemi MA, Saari TI, Hagelberg NM, Reponen P, Turpeinen M, Laine K, Neuvonen PJ, Olkkola KT. Exposure to oral S-ketamine is unaffected by itraconazole but greatly increased by ticlopidine. Clin Pharmacol Ther. 2011 Aug;90(2):296-302. doi: 10.1038/clpt.2011.140. Epub 2011 Jun 29. PubMed PMID: 21716267.
20: Peltoniemi MA, Saari TI, Hagelberg NM, Laine K, Neuvonen PJ, Olkkola KT. St John’s wort greatly decreases the plasma concentrations of oral S-ketamine. Fundam Clin Pharmacol. 2012 Dec;26(6):743-50. doi: 10.1111/j.1472-8206.2011.00954.x. Epub 2011 Jun 2. PubMed PMID: 21635359.
19: Saari TI, Uusi-Oukari M, Ahonen J, Olkkola KT. Enhancement of GABAergic activity: neuropharmacological effects of benzodiazepines and therapeutic use in anesthesiology. Pharmacol Rev. 2011 Mar;63(1):243-67. doi: 10.1124/pr.110.002717. Epub 2011 Jan 18. Review. PubMed PMID: 21245208.
18: Hagelberg NM, Nieminen TH, Saari TI, Neuvonen M, Neuvonen PJ, Laine K, Olkkola KT. Interaction of oxycodone and voriconazole-a case series of patients with cancer pain supports the findings of randomised controlled studies with healthy subjects. Eur J Clin Pharmacol. 2011 Aug;67(8):863-4. doi: 10.1007/s00228-010-0969-0. Epub 2011 Jan 11. PubMed PMID: 21221959.
17: Grönlund J, Saari TI, Hagelberg N, Neuvonen PJ, Olkkola KT, Laine K. Miconazole oral gel increases exposure to oral oxycodone by inhibition of CYP2D6 and CYP3A4. Antimicrob Agents Chemother. 2011 Mar;55(3):1063-7. doi: 10.1128/AAC.01242-10. Epub 2010 Dec 20. PubMed PMID: 21173180; PubMed Central PMCID: PMC3067090.
16: Grönlund J, Saari TI, Hagelberg NM, Neuvonen PJ, Laine K, Olkkola KT. Effect of inhibition of cytochrome P450 enzymes 2D6 and 3A4 on the pharmacokinetics of intravenous oxycodone: a randomized, three-phase, crossover, placebo-controlled study. Clin Drug Investig. 2011;31(3):143-53. doi: 10.2165/11539950-000000000-00000. PubMed PMID: 21142269.
15: Nieminen TH, Hagelberg NM, Saari TI, Neuvonen M, Neuvonen PJ, Laine K, Olkkola KT. Oxycodone concentrations are greatly increased by the concomitant use of ritonavir or lopinavir/ritonavir. Eur J Clin Pharmacol. 2010 Oct;66(10):977-85. doi: 10.1007/s00228-010-0879-1. Epub 2010 Aug 10. PubMed PMID: 20697700.
14: Grönlund J, Saari TI, Hagelberg NM, Neuvonen PJ, Olkkola KT, Laine K. Exposure to oral oxycodone is increased by concomitant inhibition of CYP2D6 and 3A4 pathways, but not by inhibition of CYP2D6 alone. Br J Clin Pharmacol. 2010 Jul;70(1):78-87. doi: 10.1111/j.1365-2125.2010.03653.x. PubMed PMID: 20642550; PubMed Central PMCID: PMC2909810.
13: Saari TI, Olkkola KT. Azole antimycotics and drug interactions in the perioperative period. Curr Opin Anaesthesiol. 2010 Aug;23(4):441-8. doi:
10.1097/ACO.0b013e32833a254d. Review. PubMed PMID: 20610983.
12: Nieminen TH, Hagelberg NM, Saari TI, Neuvonen M, Neuvonen PJ, Laine K, Olkkola KT. Grapefruit juice enhances the exposure to oral oxycodone. Basic Clin Pharmacol Toxicol. 2010 Oct;107(4):782-8. doi: 10.1111/j.1742-7843.2010.00582.x. PubMed PMID: 20406214.
11: Nieminen TH, Hagelberg NM, Saari TI, Neuvonen M, Laine K, Neuvonen PJ, Olkkola KT. St John’s wort greatly reduces the concentrations of oral oxycodone. Eur J Pain. 2010 Sep;14(8):854-9. doi: 10.1016/j.ejpain.2009.12.007. Epub 2010 Jan 27. PubMed PMID: 20106684.
10: Saari TI, Grönlund J, Hagelberg NM, Neuvonen M, Laine K, Neuvonen PJ, Olkkola KT. Effects of itraconazole on the pharmacokinetics and pharmacodynamics of intravenously and orally administered oxycodone. Eur J Clin Pharmacol. 2010 Apr;66(4):387-97. doi: 10.1007/s00228-009-0775-8. PubMed PMID: 20076952.
9: Hagelberg NM, Peltoniemi MA, Saari TI, Kurkinen KJ, Laine K, Neuvonen PJ, Olkkola KT. Clarithromycin, a potent inhibitor of CYP3A, greatly increases exposure to oral S-ketamine. Eur J Pain. 2010 Jul;14(6):625-9. doi: 10.1016/j.ejpain.2009.10.003. Epub 2009 Nov 7. PubMed PMID: 19897389.
8: Grönlund J, Saari T, Hagelberg N, Martikainen IK, Neuvonen PJ, Olkkola KT, Laine K. Effect of telithromycin on the pharmacokinetics and pharmacodynamics of oral oxycodone. J Clin Pharmacol. 2010 Jan;50(1):101-8. doi: 10.1177/0091270009336444. Epub 2009 Sep 15. PubMed PMID: 19755414.
7: Nieminen TH, Hagelberg NM, Saari TI, Pertovaara A, Neuvonen M, Laine K, Neuvonen PJ, Olkkola KT. Rifampin greatly reduces the plasma concentrations of intravenous and oral oxycodone. Anesthesiology. 2009 Jun;110(6):1371-8. doi: 10.1097/ALN.0b013e31819faa54. PubMed PMID: 19417618.
6: Hagelberg NM, Nieminen TH, Saari TI, Neuvonen M, Neuvonen PJ, Laine K, Olkkola KT. Voriconazole drastically increases exposure to oral oxycodone. Eur J Clin Pharmacol. 2009 Mar;65(3):263-71. doi: 10.1007/s00228-008-0568-5. Epub 2008 Oct 3. PubMed PMID: 18836708.
5: Saari TI, Laine K, Neuvonen M, Neuvonen PJ, Olkkola KT. Effect of voriconazole and fluconazole on the pharmacokinetics of intravenous fentanyl. Eur J Clin Pharmacol. 2008 Jan;64(1):25-30. Epub 2007 Nov 7. PubMed PMID: 17987285.
4: Saari TI, Laine K, Bertilsson L, Neuvonen PJ, Olkkola KT. Voriconazole and fluconazole increase the exposure to oral diazepam. Eur J Clin Pharmacol. 2007 Oct;63(10):941-9. Epub 2007 Aug 4. PubMed PMID: 17676319.
3: Saari TI, Laine K, Leino K, Valtonen M, Neuvonen PJ, Olkkola KT. Voriconazole, but not terbinafine, markedly reduces alfentanil clearance and prolongs its half-life. Clin Pharmacol Ther. 2006 Nov;80(5):502-8. PubMed PMID: 17112806.
2: Saari TI, Laine K, Leino K, Valtonen M, Neuvonen PJ, Olkkola KT. Effect of voriconazole on the pharmacokinetics and pharmacodynamics of zolpidem in healthy subjects. Br J Clin Pharmacol. 2007 Jan;63(1):116-20. Epub 2006 Jul 6. PubMed PMID: 16822278; PubMed Central PMCID: PMC2000716.
1: Saari TI, Laine K, Leino K, Valtonen M, Neuvonen PJ, Olkkola KT. Effect of voriconazole on the pharmacokinetics and pharmacodynamics of intravenous and oral midazolam. Clin Pharmacol Ther. 2006 Apr;79(4):362-70. PubMed PMID: 16580904.