Effects of ketoconazole and quinidine on pharmacokinetics of pactimibe and its plasma metabolite, R-125528, in humans

Drug Metabolism and Disposition

Volumn 36, Issue 8, 2008, Pages 1505-1511

  Kotsuma, Masakatsu ^a   Tokui, Taro ^a   Freudenthaler, Stefan ^a   Nishimura, Kenji ^a  

^a DAIICHI SANKYO CO   (Japan)

Author keywords

[No Author keywords available]

Indexed keywords

CHOLESTEROL ACYLTRANSFERASE INHIBITOR; CYTOCHROME P450 2D6; CYTOCHROME P450 3A4; DRUG METABOLITE; KETOCONAZOLE; PACTIMIBE; QUINIDINE; R 125528;

ACIDITY; ADULT; AREA UNDER THE CURVE; ARTICLE; ATHEROSCLEROSIS; CLINICAL TRIAL; CONTROLLED CLINICAL TRIAL; CONTROLLED STUDY; CROSSOVER PROCEDURE; DOUBLE BLIND PROCEDURE; DRUG BLOOD LEVEL; DRUG CROSS REACTIVITY; DRUG ELIMINATION; DRUG METABOLISM; HUMAN; HUMAN CELL; HUMAN EXPERIMENT; HUMAN TISSUE; HYPERCHOLESTEROLEMIA; IN VITRO STUDY; MALE; MORNING DOSAGE; NORMAL HUMAN; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL; SINGLE DRUG DOSE;

ADULT; ALKANES; AREA UNDER CURVE; CROSS-OVER STUDIES; DOSE-RESPONSE RELATIONSHIP, DRUG; DOUBLE-BLIND METHOD; DRUG INTERACTIONS; ENZYME INHIBITORS; HUMANS; INDOLEACETIC ACIDS; INDOLES; KETOCONAZOLE; MALE; PLACEBOS; QUINIDINE; SENSITIVITY AND SPECIFICITY;

EID: 47949093035     PISSN: 00909556     EISSN: 1521009X     Source Type: Journal    
DOI: 10.1124/dmd.108.021394     Document Type: Article

References (32)

1. Bjornsson TD, Callaghan JT, Einolf HJ, Fischer V, Gan L, Grimm S, Kao J, King SP, Miwa G, Ni L, et al (2003) The conduct of in vitro and in vivo drug-drug interaction studies: a PhRMA perspective. J Clin Pharmacol 43:443-469.
2. Brinn R, Brøsen K, Gram LF, Haghfelt T, and Otton SV (1986) Sparteine oxidation is practically abolished in quinidine-treated patients. Br J Clin Pharmacol 22:194-197.
3. Brøsen K, Gram LF, Haghfelt T, and Bertilsson L (1987) Extensive metabolizers of debrisoquine become poor metabolizers during quinidine treatment. Pharmacol Toxicol 60:312-314.
4. Center for Drug Evaluation and Research (2006) In Vivo Drug Metabolism/Drug Interaction Studies-Study Design, Data Analysis, and Recommendations for Dosing and Labeling. U.S. Food and Drug Administration, Washington, DC.
5. Ellis SW, Hayhurst GP, Smith G, Lightfoot T, Wong MM, Simula AP, Ackland MJ, Sternberg MJ, Lennard MS, Tucker GT, et al. (1995) Evidence that aspartic acid 301 is a critical substrate-contact residue in the active site of cytochrome P450 2D6. J Biol Chem 270:29055-29058.
6. Gibbs JP, Hyland R, and Youdim K (2006) Minimizing polymorphic metabolism in drug discovery: evaluation of the utility of in vitro methods for predicting pharmacokinetic consequences associated with CYP2D6 metabolism. Drug Metab Dispos 34:1516-1522.
7. Guengerich FP, Miller GP, Hanna IH, Martin MV, Leger S, Black C, Chauret N, Silva JM, Trimble LA, Yergey JA, et al. (2002) Diversity in the oxidation of substrates by cytochrome P450 2D6: lack of an obligatory role of aspartate 301-substrate electrostatic bonding. Biochemistry 41:11025-11034.
8. Hainer JW, Terry JG, Connell JM, Zyruk H, Jenkins RM, Shand DL, Gillies PJ, Livak KJ, Hunt TL, and Crouse JR 3rd (1994) Effect of the acyl-CoA:cholesterol acyltransferase inhibitor DuP 128 on cholesterol absorption and serum cholesterol in humans. Clin Pharmacol Ther 56:65-74.
9. Harris WS, Dujovne CA, von Bergmann K, Neal J, Akester J, Windsor SL, Greene D, and Look Z (1990) Effects of the ACAT inhibitor CL 277,082 on cholesterol metabolism in humans. Clin Pharmacol Ther 48:189-194.
10. Ishi M, Tomono Y, Sanma H, Yamoto C, Sekino H, Nomura M, and Nakaya N (1994) Pharmacokinetics of novel ACAT inhibitor E5324, in healthy volunteers. Atherosclerosis 109:283 (253-Abstract).
11. Ito K, Brown HS, and Houston JB (2004) Database analyses for the prediction of in vivo drug-drug interactions from in vitro data. Br J Clin Pharmacol 57:473-486.
12. Ito K, Hallifax D, Obach RS, and Houston JB (2005) Impact of parallel pathways of drug elimination and multiple cytochrome P450 involvement on drug-drug interactions: CYP2D6 paradigm. Drug Metab Dispos 33:837-844.
13. Ito K, Iwatsubo T, Kanamitsu S, Ueda K, Suzuki H, and Sugiyama Y (1998) Prediction of pharmacokinetic alterations caused by drug-drug interactions: metabolic interaction in the liver. Pharmacol Rev 50:387-412.
14. Jones TE (1997) The use of other drugs to allow a lower dosage of cyclosporin to be used: therapeutic and pharmacoeconomic considerations. Clin Pharmacokinet 32:357-367.
15. Kashiwa M, Masuyama Y, Miyauchi H, Uchida T, Naganuma S, Kakuta H, Terada M, Kiriyama T, Matsuda K, Ito N, et al. (1997) Pharmacological properties of YM17E, an acyl-CoA: cholesterol acyltransferase inhibitor, and diarrheal effect in beagle dogs. Jpn J Pharmacol 73:41-50.
16. Kitayama K, Koga T, Inaba T, and Fujioka T (2006a) Multiple mechanisms of hypocholesterolemic action of pactimibe, a novel acyl-coenzyme A:cholesterol acyltransferase inhibitor. Eur J Pharmacol 543:123-132.
17. Kitayama K, Koga T, Maeda N, Inaba T, and Fujioka T (2006b) Pactimibe stabilizes atherosclerotic plaque through macrophage acyl-CoA:cholesterol acyltransferase inhibition in WHHL rabbits. Eur J Pharmacol 539:81-88.
18. Kitayama K, Tanimoto T, Koga T, Terasaka N, Fujioka T, and Inaba T (2006c) Importance of acyl-coenzyme A:cholesterol acyltransferase 1/2 dual inhibition for anti-atherosclerotic potency of pactimibe. Eur J Pharmacol 540:121-130.
19. Kotsuma M, Tokui T, Ishizuka-Ozeki T, Honda T, Iwabuchi H, Murai T, Ikeda T, and Saji H (2008) CYP2D6-mediated metabolism of a novel acyl coenzyme A:cholesterol acyltransferase inhibitor, pactimibe, and its unique plasma metabolite, R-125528. Drug Metab Dispos 36:529-534.
20. Matsuo M, Hashimoto M, Suzuki J, Iwanami K, Tomoi M, and Shimomura K (1996) Difference between normal and WHHL rabbits in susceptibility to the adrenal toxicity of an acyl-CoA: cholesterol acyltransferase inhibitor, FR145237. Toxicol Appl Pharmacol 140:387-392.
21. Nakaya N, Nakamichi N, Sekino H, Nomura M, Ishii M, Tomono Y, and Yamato C (1994) Effect of a novel ACAT inhibitor, E5324, on serum lipids and lipoproteins in healthy volunteers. Atherosclerosis 109:284 (253-Abstract).
22. Nissen SE, Tuzcu EM, Brewer HB, Sipahi I, Nicholls SJ, Ganz P, Schoenhagen P, Waters DD, Pepine CJ, Crowe TD, et al. (2006) Effect of ACAT inhibition on the progression of coronary atherosclerosis. N Engl J Med 354:1253-1263.
23. Niwa T, Shiraga T, and Takagi A (2005) Drug-drug interaction of antifungal drugs. Yakugaku Zasshi 125:795-805.
24. Olkkola KT, Backman JT, and Neuvonen PJ (1994) Midazolam should be avoided in patients receiving the systemic antimycotics ketoconazole or itraconazole. Clin Pharmacol Ther 55:481-485.
25. Paine MJ, McLaughlin LA, Flanagan JU, Kemp CA, Sutcliffe MJ, Roberts GC, and Wolf CR (2003) Residues glutamate 216 and aspartate 301 are key determinants of substrate specificity and product regioselectivity in cytochrome P450 2D6. J Biol Chem 278:4021-4027.
26. Palkama VJ, Ahonen J, Neuvonen PJ, and Olkkola KT (1999) Effect of saquinavir on the pharmacokinetics and pharmacodynamics of oral and intravenous midazolam. Clin Pharmacol Ther 66:33-39.
27. Reindel JF, Dominick MA, Bocan TM, Gough AW, and McGuire EJ (1994) Toxicologic effects of a novel acyl-CoA:cholesterol acyltransferase inhibitor in cynomolgus monkeys. Toxicol Pathol 22:510-518.
28. Tardif JC, Gregoire J, L'Allier PL, Anderson TJ, Bertrand O, Reeves F, Title LM, Alfonso F, Schampaert E, Hassan A, et al. (2004) Effects of the acyl coenzyme A:cholesterol acyltransferase inhibitor avasimibe on human atherosclerotic lesions. Circulation 110:3372-3377.
29. Terasaka N, Miyazaki A, Kasanuki N, Ito K, Ubukata N, Koieyama T, Kitayama K, Tanimoto T, Maeda N, and Inaba T (2007) ACAT inhibitor pactimibe sulfate (CS-505) reduces and stabilizes atherosclerotic lesions by cholesterol-lowering and direct effects in apolipoprotein E-deficient mice. Atherosclerosis 190:239-247.
30. Vernetti LA, MacDonald JR, Wolfgang GH, Dominick MA, and Pegg DG (1993) ATP depletion is associated with cytotoxicity of a novel lipid regulator in guinea pig adrenocortical cells. Toxicol Appl Pharmacol 118:30-38.
31. von Moltke LL, Greenblatt DJ, Harmatz JS, Duan SX, Harrel LM, Cotreau-Bibbo MM, Pritchard GA, Wright CE, and Shader RI (1996) Triazolam biotransformation by human liver microsomes in vitro: effects of metabolic inhibitors and clinical confirmation of a predicted interaction with ketoconazole. J Pharmacol Exp Ther 276:370-379.
32. Zhou HH, Anthony LB, Roden DM, and Wood AJ (1990) Quinidine reduces clearance of (+)-propranolol more than (-)-propranolol through marked reduction in 4-hydroxylation. Clin Pharmacol Ther 47:686-693.