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Pharmacokinetic Drug Interaction Profiles of Proton Pump Inhibitors

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Abstract

Proton pump inhibitors are used extensively for the treatment of gastric acid-related disorders because they produce a greater degree and longer duration of gastric acid suppression and, thus, better healing rates, than histamine H2 receptor antagonists. The need for long-term treatment of these disorders raises the potential for clinically significant drug interactions in patients receiving proton pump inhibitors and other medications. Therefore, it is important to understand the mechanisms for drug interactions in this setting. Proton pump inhibitors can modify the intragastric release of other drugs from their dosage forms by elevating pH (e.g. reducing the antifungal activity of ketoconazole). Proton pump inhibitors also influence drug absorption and metabolism by interacting with adenosine triphosphate-dependent P-glycoprotein (e.g. inhibiting digoxin efflux) or with the cytochrome P450 (CYP) enzyme system (e.g. decreasing simvastatin metabolism), thereby affecting both intestinal first-pass metabolism and hepatic clearance.

Although interactions based on the change of gastric pH are a group-specific effect and thus may occur with all proton pump inhibitors, individual proton pump inhibitors differ in their propensities to interact with other drugs and the extent to which their interaction profiles have been defined. The interaction profiles of omeprazole and pantoprazole have been studied most extensively. A number of studies have shown that omeprazole carries a considerable potential for drug interactions, since it has a high affinity for CYP2C19 and a somewhat lower affinity for CYP3A4. In contrast, pantoprazole appears to have lower potential for interactions with other medications. Although the interaction profiles of esomeprazole, lansoprazole and rabeprazole have been less extensively investigated, evidence suggests that lansoprazole and rabeprazole seem to have a weaker potential for interactions than omeprazole.

Although only a few drug interactions involving proton pump inhibitors have been shown to be of clinical significance, the potential for drug interactions should be taken into account when choosing a therapy for gastric acid-related disorders, especially for elderly patients in whom polypharmacy is common, or in those receiving a concomitant medication with a narrow therapeutic index.

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References

  1. Horn J. The proton-pump inhibitors: similarities and differences. Clin Ther 2000; 22: 266–80

    Article  PubMed  CAS  Google Scholar 

  2. Farup PG, Juul-Hansen PH, Rydning A. Does short-term treatment with proton pump inhibitors cause rebound aggravation of symptoms? J Clin Gastroenterol 2001; 33: 206–9

    Article  PubMed  CAS  Google Scholar 

  3. Gillen D, Wirz AA, McColl KE. Helicobacter pylori eradication releases prolonged increased acid secretion following omeprazole treatment. Gastroenterology 2004; 126: 980–8

    Article  PubMed  CAS  Google Scholar 

  4. Chiba N, De Gara CJ, Wilkinson JM, et al. Speed of healing and symptom relief in grade II to IV gastroesophageal reflux disease: a meta-analysis. Gastroenterology 1997; 112: 1798–810

    Article  PubMed  CAS  Google Scholar 

  5. Dammann HG. Pantoprazole: a pharmacological and clinical profile. Today’s Ther Trends 1997; 15: 109–36

    Google Scholar 

  6. Cheer SM, Prakash A, Faulds D, et al. Pantoprazole: an update of its pharmacological properties and therapeutic use in the management of acid-related disorders. Drugs 2003; 63: 101–32

    Article  PubMed  CAS  Google Scholar 

  7. Welage LS, Berardi RR. Evaluation of omeprazole, lansoprazole, pantoprazole, and rabeprazole in the treatment of acid-related diseases. J Am Pharm Assoc (Wash) 2000; 40: 52–62

    CAS  Google Scholar 

  8. Lanza FL. A guideline for the treatment and prevention of NSAID-induced ulcers. Members of the Ad Hoc Committee on Practice Parameters of the American College of Gastroenterology. Am J Gastroenterol 1998; 93: 2037–46

    Article  PubMed  CAS  Google Scholar 

  9. Singh G, Triadafilopoulos G. Appropriate choice of proton pump inhibitor therapy in the prevention and management of NSAID-related gastrointestinal damage. Int J Clin Pract 2005; 59: 1210–7

    Article  PubMed  CAS  Google Scholar 

  10. Humphries TJ, Merritt GJ. Drug interactions with agents used to treat acid-related diseases. Aliment Pharmacol Ther 1999; 13Suppl. 3: 18–26

    Article  PubMed  CAS  Google Scholar 

  11. Johnson AG, Seidemann P, Day RO. NSAID-related adverse drug interactions with clinical relevance: an update. Int J Clin Pharmacol Ther 1994; 32: 509–32

    PubMed  CAS  Google Scholar 

  12. Triadafilopoulos G, Sharma R. Features of symptomatic gastroesophageal reflux disease in elderly patients. Am J Gastroenterol 1997; 92: 2007–11

    PubMed  CAS  Google Scholar 

  13. Chutka DS, Evans JM, Fleming KC, et al. Drug prescribing for elderly patients. Mayo Clin Proc 1995; 70: 685–93

    Article  PubMed  CAS  Google Scholar 

  14. Ramirez FC. Diagnosis and treatment of gastroesophageal reflux disease in the elderly. Cleve Clin J Med 2000; 67: 755–65

    PubMed  CAS  Google Scholar 

  15. Gerson LB, Triadafilopoulos G. Proton pump inhibitors and their drug interactions: an evidence-based approach. Eur J Gastroenterol Hepatol 2001; 13: 611–6

    Article  PubMed  CAS  Google Scholar 

  16. Hanlon JT, Schmader KE, Koronkowski MJ, et al. Adverse drug events in high risk older outpatients. J Am Geriatr Soc 1997; 45: 945–8

    PubMed  CAS  Google Scholar 

  17. Lazarou J, Pomeranz BH, Corey PN. Incidence of adverse drug reactions in hospitalized patients: a meta-analysis of prospective studies. JAMA 1998; 279: 1200–5

    Article  PubMed  CAS  Google Scholar 

  18. Lamy PP. Pharmacotherapeutics in the elderly. Md Med J 1989; 38: 144–8

    PubMed  CAS  Google Scholar 

  19. Stewart RB, Cooper JW. Polypharmacy in the aged: practical solutions. Drugs Aging 1994; 4: 449–61

    Article  PubMed  CAS  Google Scholar 

  20. Shapiro LE, Shear NH. Drug interactions: proteins, pumps, and P-450s. J Am Acad Dermatol 2002; 47: 467–84

    Article  PubMed  Google Scholar 

  21. Reynolds JC. The clinical importance of drug interactions with antiulcer therapy. J Clin Gastroenterol 1990; 12Suppl. 2: 54S–63S

    Article  Google Scholar 

  22. Vanderhoff BT, Tahboub RM. Proton pump inhibitors: an update. Am Fam Physician 2002; 66: 273–80

    PubMed  Google Scholar 

  23. Chin TW, Loeb M, Fong IW. Effects of an acidic beverage (Coca-Cola) on absorption of ketoconazole. Antimicrob Agents Chemother 1995; 39: 1671–5

    Article  PubMed  CAS  Google Scholar 

  24. Carlson JA, Mann HJ, Canafax DM. Effect of pH on disintegration and dissolution of ketoconazole tablets. Am J Hosp Pharm 1983; 40: 1334–6

    PubMed  CAS  Google Scholar 

  25. Jaruratanasirikul S, Sriwiriyajan S. Effect of omeprazole on the pharmacokinetics of itraconazole. Eur J Clin Pharmacol 1998; 54: 159–61

    Article  PubMed  CAS  Google Scholar 

  26. Johnson MD, Hamilton CD, Drew RH, et al. A randomized comparative study to determine the effect of omeprazole on the peak serum concentration of itraconazole oral solution. J Antimicrob Chemother 2003; 51: 453–7

    Article  PubMed  CAS  Google Scholar 

  27. Burger DM, Hugen PWH, Kroon FP, et al. Pharmacokinetic interaction between the proton pump inhibitor omeprazole and the HIV protease inhibitor indinavir. AIDS 1998; 12: 2080–2

    Article  PubMed  CAS  Google Scholar 

  28. Treiber G, Walker S, Klotz U. Omeprazole-induced increase in the absorption of bismuth from tripotassium dicitrato bismuthate. Clin Pharmacol Ther 1994; 55: 486–91

    Article  PubMed  CAS  Google Scholar 

  29. Pauli-Magnus C, Rekersbrink S, Klotz U, et al. Interaction of omeprazole, lansoprazole and pantoprazole with P-glycoprotein. Naunyn Schniedebergs Arch Pharmacol 2001; 364: 551–7

    Article  CAS  Google Scholar 

  30. Cummins CL, Jacobsen W, Benet LZ. Unmasking the dynamic interplay between intestinal P-glycoprotein and CYP3A4. J Pharmacol Exp Ther 2002; 300: 1036–45

    Article  PubMed  CAS  Google Scholar 

  31. Meyer UA. Overview of enzymes of drug metabolism. J Pharmacokinet Biopharm 1996; 24: 449–59

    PubMed  CAS  Google Scholar 

  32. Kolars JC, Awni WM, Merion RM, et al. First-pass metabolism of cyclosporin by the gut. Lancet 1991; 338: 1488–90

    Article  PubMed  CAS  Google Scholar 

  33. Paine MF, Shen DD, Kunze KL, et al. First-pass metabolism of midazolam by the human intestine. Clin Pharmacol Ther 1996; 60: 14–24

    Article  PubMed  CAS  Google Scholar 

  34. Shen DD, Kunze KL, Thummel KE. Enzyme-catalyzed processes of first-pass hepatic and intestinal drug extraction. Adv Drug Deliv Rev 1997; 27: 99–127

    Article  PubMed  Google Scholar 

  35. Lown K, Balley D, Fontana R, et al. Grapefruit juice increases felodipine oral bioavailability in humans by decreasing intestinal CYP3A protein expression. J Clin Invest 1997; 99: 2545–53

    Article  PubMed  CAS  Google Scholar 

  36. Martin J, Krum H. Cytochrome P450 drug interactions within the HMG-CoA reductase inhibitor class: are they clinically relevant? Drug Saf 2003; 26: 13–21

    Article  PubMed  CAS  Google Scholar 

  37. Li XQ, Andersson TB, Ahlstrom M, et al. Comparison of inhibitory effects of the proton pump-inhibiting drugs omeprazole, esomeprazole, lansoprazole, pantoprazole, and rabeprazole on human cytochrome P450 activities. Drug Metab Dispos 2004; 32: 821–7

    Article  PubMed  CAS  Google Scholar 

  38. Simon WA. Faster in vitro biotransformation of S-omeprazole by the cytochrome P450 isoenzyme system compared to pantoprazole [abstract]. Pharmacotherapy 2003; 23: 1338

    Google Scholar 

  39. Bliesath H, Huber R, Steinijans VW, et al. Lack of pharmacokinetic interaction between pantoprazole and diclofenac. Int J Clin Pharmacol Ther 1996; 34: 152–6

    PubMed  CAS  Google Scholar 

  40. Karol MD, Locke CS, Cavanaugh JH. Lack of pharmacokinetic interaction between lansoprazole and intravenously administered phenytoin. J Clin Pharmacol 1999; 39: 1283–9

    Article  PubMed  CAS  Google Scholar 

  41. Krusekopf S, Roots I, Hildebrandt AG, et al. Time-dependent transcriptional induction of CYP1A1, CYP1A2 and CYP1B1 mRNAs by H+/K+-ATPase inhibitors and other xenobiotics. Xenobiotica 2003; 33: 107–18

    Article  PubMed  CAS  Google Scholar 

  42. Gerloff J, Barth H, Mignot A, et al. Does the proton pump inhibitor lansoprazole interact with antacids [abstract]. Arch Pharmacol 1993; 347: A124

    Google Scholar 

  43. Gremse DA. Lansoprazole: pharmacokinetics, pharmacodynamics and clinical uses. Expert Opin Pharmacother 2001; 2: 1663–70

    Article  PubMed  CAS  Google Scholar 

  44. Iwao K, Saitoh H, Takeda K, et al. Decreased plasma levels of omeprazole after coadministration with magnesium-aluminium hydroxide dry suspension granules. Yakugaku Zasshi 1999; 119: 221–8

    PubMed  CAS  Google Scholar 

  45. Hartmann M, Bliesath H, Huber R, et al. Simultaneous intake of antacids has no influence on the pharmacokinetics of the gastric H+/K+-ATPase inhibitor pantoprazole [abstract]. Gut 1994; 35Suppl. 4: A76

    Google Scholar 

  46. Yasuda S, Higashi S, Murakami M, et al. Antacids have no influence on the pharmacokinetics of rabeprazole, a new proton pump inhibitor, in healthy volunteers. Int J Clin Pharmacol Ther 1999; 37: 249–53

    PubMed  CAS  Google Scholar 

  47. St Peter JV, Awni WM, Granneman GR, et al. The effects of lansoprazole on the disposition of antipyrine and indocyanine green in normal human subjects. Am J Ther 1995; 2: 561–8

    Article  PubMed  Google Scholar 

  48. De Mey C, Meineke I, Steinijans VW, et al. Pantoprazole lacks interaction with antipyrine in man, either by inhibition or induction. Int J Clin Pharmacol Ther 1994; 32: 98–106

    PubMed  Google Scholar 

  49. Andersson T, Holmberg J, Rohss K, et al. Pharmacokinetics and effect on caffeine metabolism of the proton pump inhibitors, omeprazole, lansoprazole, and pantoprazole. Br J Clin Pharmacol 1998; 45: 369–75

    Article  PubMed  CAS  Google Scholar 

  50. Rost KL, Roots I. Accelerated caffeine metabolism after omeprazole treatment indicated by urinary metabolic ratios: coincidence with plasma clearance and breath test. Clin Pharmacol Ther 1994; 55: 402–11

    Article  PubMed  CAS  Google Scholar 

  51. Hartmann M, Zech K, Bliesath H, et al. Pantoprazole lacks induction of CYP1A2 activity in man. Int J Clin Pharmacol Ther 1999; 37: 159–64

    PubMed  CAS  Google Scholar 

  52. Naidu MUR, Shobha JC, Dixit VK, et al. Effect of multiple dose omeprazole on the pharmacokinetics of carbamazepine. Drug Invest 1994; 7: 8–12

    Article  Google Scholar 

  53. Huber R, Bliesath H, Hartmann M, et al. Pantoprazole does not interact with the pharmacokinetics of carbamazepine. Int J Clin Pharmacol Ther 1998; 36: 521–4

    PubMed  CAS  Google Scholar 

  54. Colin-Jones DG. Safety of lansoprazole. Aliment Pharmacol Ther 1993; 7Suppl. 1: 56–60

    PubMed  Google Scholar 

  55. Middle MV, Müller FO, Schall R, et al. Effect of pantoprazole on ovulation suppression by a low-dose hormonal contraceptive. Clin Drug Invest 1995; 9: 54–6

    Google Scholar 

  56. Schouler L, Dumas F, Couzigou P, et al. Omeprazolecyclosporin interaction [abstract]. Am J Gastroenterol 1991; 86: 1097

    PubMed  CAS  Google Scholar 

  57. Reichenspurner H, Meiser BM, Muschiol F, et al. The influence of gastrointestinal agents on resorption and metabolism of cyclosporine after heart transplantation: experimental and clinical results. J Heart Lung Transplant 1993; 12(6 Pt 1): 987–92

    PubMed  CAS  Google Scholar 

  58. Blohme I, Idstrom JP, Andersson T. A study of the interaction between omeprazole and cyclosporine in renal transplant patients. Br J Clin Pharmacol 1993; 35: 156–60

    PubMed  CAS  Google Scholar 

  59. Lorf T, Ramadori G, Ringe B, et al. Pantoprazole does not affect ciclosporin A blood concentration in kidney-transplant patients. Eur J Clin Pharmacol 2000; 55: 733–5

    Article  PubMed  CAS  Google Scholar 

  60. Padhi D, Harris R, Salfi M, et al. Cinacalcet HCl absorption in study subjects is not affected by coadministration of medications commonly prescribed to chronic kidney disease (CKD) patients (pantoprazole, sevelamar HCl, and calcium carbonate) [abstract]. J Am Soc Nephrol 2003; 14: SA–PO744

    Google Scholar 

  61. Andersson T, Hassan-lin M, Hasselgren G, et al. Pharmacokinetic studies with esomeprazole, the (S)-somer of omeprazole. Clin Pharmacokinet 2001; 40: 411–26

    Article  PubMed  CAS  Google Scholar 

  62. Andersson T, Hassan-lin M, Hasselgren G, et al. Drug interaction studies with esomeprazole, the (S)-somer of omeprazole. Clin Pharmacokinet 2001; 40: 523–37

    Article  PubMed  CAS  Google Scholar 

  63. Drewelow B, Schaffler K, Reitmeir P. Superior interaction profile of pantoprazole vs esomeprazole after single dose diazepam regarding pharmacodynamic (PD) and kinetic (PK) parameters. Can J Gastroenterol 2006; 20Suppl. A: 144

    Google Scholar 

  64. Lefebvre RA, Flouvat B, Karolac-Tamisier S, et al. Influence of lansoprazole treatment on diazepam plasma concentrations. Clin Pharmacol Ther 1992; 52: 458–63

    Article  PubMed  CAS  Google Scholar 

  65. Andersson T, Cederberg C, Edvardsson G, et al. Effect of omeprazole treatment on diazepam plasma levels in slow versus normal rapid metabolizers of omeprazole. Clin Pharmacol Ther 1990; 47: 79–85

    Article  PubMed  CAS  Google Scholar 

  66. Gugler R, Jensen JC. Omeprazole inhibits oxidative drug metabolism: studies with diazepam and phenytoin in vivo and 7-ethoxycoumarin in vitro. Gastroenterology 1985; 89: 1235–41

    PubMed  CAS  Google Scholar 

  67. Gugler R, Hartmann M, Rudi J, et al. Lack of pharmacokinetic interaction of pantoprazole with diazepam in man. Br J Clin Pharmacol 1996; 42: 249–52

    Article  PubMed  CAS  Google Scholar 

  68. Ishizaki T, Chiba K, Manabe K, et al. Comparison of the interaction potential of a new proton pump inhibitor, E3810, versus omeprazole with diazepam in extensive and poor metabolizers of S-mephenytoin 4′-hydroxylation. Clin Pharmacol Ther 1995; 58: 155–64

    Article  PubMed  CAS  Google Scholar 

  69. Andersson T, Bredberg E, Lagerstrom PO, et al. Lack of drug-drug interaction between three different non-steroidal anti-inflammatory drugs and omeprazole. Eur J Clin Pharmacol 1998; 54: 399–404

    Article  PubMed  CAS  Google Scholar 

  70. Oosterhuis B, Jonkman JH, Andersson T, et al. Minor effect of multiple dose omeprazole on the pharmacokinetics of digoxin after a single oral dose. Br J Clin Pharmacol 1991; 32: 569–72

    Article  PubMed  CAS  Google Scholar 

  71. Hartmann M, Huber R, Bliesath H, et al. Lack of interaction between pantoprazole and digoxin at therapeutic doses in man. Int J Clin Pharmacol Ther 1996; 34(1 Suppl.): 67S–71S

    Google Scholar 

  72. Fuhr U, Jetter A. Rabeprazole: pharmacokinetic and pharmacokinetic drug interactions. Pharmazie 2002; 57: 595–601

    PubMed  CAS  Google Scholar 

  73. Battison L, Tulissi P, Moretti M, et al. Lansoprazole and ethanol metabolism: comparison with omeprazole and cimetidine. Pharmacol Toxicol 1997; 81: 247–52

    Google Scholar 

  74. Heinze H, Fischer R, Pfutzer R, et al. Lack of interaction between pantoprazole and ethanol. Clin Drug Invest 2001; 21: 345–51

    Article  CAS  Google Scholar 

  75. Walter-Sack IE, Bliesath H, Stotzer F, et al. Lack of pharmacokinetic and pharmacodynamic interaction between pantoprazole and glibenclamide in humans. Clin Drug Invest 1998; 15: 253–60

    Article  CAS  Google Scholar 

  76. Dietrich JW, Gleselbrecht K, Holl RW, et al. Absorption kinetic of levothyroxine is not altered by proton-pump inhibitor therapy. Horm Metab Res 2006; 38: 57–9

    Article  PubMed  CAS  Google Scholar 

  77. Andersson T, Lundborg P, Regardh CG. Lack of effect of omeprazole treatment on steady-state plasma levels of metoprolol. Eur J Clin Pharmacol 1991; 40: 61–5

    Article  PubMed  CAS  Google Scholar 

  78. Koch HJ, Hartmann M, Bliesath H, et al. Pantoprazole has no influence on steady state pharmacokinetics and pharmacodynamics of metoprolol in healthy volunteers. Int J Clin Pharmacol Ther 1996; 34: 420–3

    PubMed  CAS  Google Scholar 

  79. Hartmann M, Schulz HU, Krupp S, et al. Pantoprazole lacks interaction with the NSAID naproxen in man [abstract]. Gut 2000; 47: A85

    Google Scholar 

  80. Soons P, van der Berg G, Danhof M, et al. Influence of single- and multiple-dose omeprazole treatment on nifedipine pharmacokinetics and effects in healthy subjects. Eur J Clin Pharmacol 1992; 42: 319–24

    Article  PubMed  CAS  Google Scholar 

  81. Bliesath H, Huber R, Steinijans VW, et al. Pantoprazole does not interact with nifedipine in man under steady-state conditions. Int J Clin Pharmacol Ther 1996; 34: 51–5

    PubMed  CAS  Google Scholar 

  82. Enderle C, Muller W, Grass U. Drug interaction: omeprazole and phenprocoumon [abstract]. BMC Gastroenterol 2001; 1: 2

    Article  PubMed  CAS  Google Scholar 

  83. Ehrlich A, Fuder H, Hartmann M, et al. Lack of pharmacodynamic and pharmacokinetic interaction between pantoprazole and phenprocoumon in man. Eur J Clin Pharmacol 1996; 51: 277–81

    Article  PubMed  CAS  Google Scholar 

  84. Prichard PJ, Walt RP, Kitchingman GK, et al. Oral phenytoin pharmacokinetics during omeprazole therapy. Br J Clin Pharmacol 1987; 24: 543–5

    Article  PubMed  CAS  Google Scholar 

  85. Andersson T, Lagerstrom PO, Unge P. A study of the interaction between omeprazole and phenytoin in epileptic patients. Ther Drug Monit 1990; 12: 329–33

    Article  PubMed  CAS  Google Scholar 

  86. Middle MV, Muller FO, Schall R, et al. No influence of pantoprazole on the pharmacokinetics of phenytoin. Int J Clin Pharmacol Ther 1995; 33: 304–7

    PubMed  CAS  Google Scholar 

  87. Humphries TJ. A review of the drug-drug interaction potential of rabeprazole sodium based on CYP-450 interference or absorption effects [abstract]. Digestion 1998; 59Suppl. 3: 76

    Google Scholar 

  88. Bliesath H, Hartmann M, Maier J, et al. Lack of interaction between pantoprazole and piroxicam in man [abstract]. Gut 2000; 47: A85

    Google Scholar 

  89. Itagaki F, Homma M, Yuzawa K, et al. Drug interaction of tacrolimus and proton pump inhibitors in renal transplant recipients with CYP2C19 gene mutation. Transplant Proc 2002; 34: 2777–8

    Article  PubMed  CAS  Google Scholar 

  90. Lorf T, Ramadori G, Ringe B, et al. The effect of pantoprazole on tacrolimus and cyclosporin A blood concentration in transplant recipients. Eur J Clin Pharmacol 2000; 56: 439–40

    Article  PubMed  CAS  Google Scholar 

  91. Dilger K, Zheng Z, Klotz U. Lack of drug interaction between omeprazole, lansoprazole, pantoprazole and theophylline. Br J Clin Pharmacol 1999; 48: 438–44

    Article  PubMed  CAS  Google Scholar 

  92. Granneman GR, Karol MD, Locke CS, et al. Pharmacokinetic interaction between lansoprazole and theophylline. Ther Drug Monit 1995; 17: 460–4

    Article  PubMed  CAS  Google Scholar 

  93. Taburet AM, Geneve J, Bocquentin M, et al. Theophylline steady state pharmacokinetics is not altered by omeprazole. Eur J Clin Pharmacol 1992; 42: 343–5

    Article  PubMed  CAS  Google Scholar 

  94. Schulz HU, Hartmann M, Steinijans VW, et al. Lack of influence of pantoprazole on the disposition kinetics of theophylline in man. Int J Clin Pharmacol Ther Toxicol 1991; 29: 369–75

    PubMed  CAS  Google Scholar 

  95. Humphries TJ, Nardi RV, Spera AC, et al. Coadministration of rabeprazole sodium (E3810) does not affect the pharmacokinetics of anhydrous theophylline or warfarin [abstract]. Gastroenterology 1996; 110: A138

    Google Scholar 

  96. Sutfin T, Balmer K, Bostrom H, et al. Stereoselective interaction of omeprazole with warfarin in health men. Ther Drug Monit 1989; 11: 176–84

    Article  PubMed  CAS  Google Scholar 

  97. Unge P, Svedberg LE, Nordgren A, et al. A study of the interaction of omeprazole and warfarin in anticoagulated patients. Br J Clin Pharmacol 1992; 34: 509–12

    Article  PubMed  CAS  Google Scholar 

  98. Duursema L, Muller FO, Schall R, et al. Lack of effect of pantoprazole on the pharmacodynamics and pharmacokinetics of warfarin. Br J Clin Pharmacol 1995; 39: 700–3

    Article  PubMed  CAS  Google Scholar 

  99. Howden CW. Clinical pharmacology of omeprazole. Clin Pharmacokinet 1991; 20: 38–49

    Article  PubMed  CAS  Google Scholar 

  100. Andersson T, Miners JO, Veronese ME, et al. Identification of human liver cytochrome P450 isoforms mediating omeprazole metabolism. Br J Clin Pharmacol 1993; 36: 521–30

    Article  PubMed  CAS  Google Scholar 

  101. Funck-Brentano C, Becquemont L, Leneveu A, et al. Inhibition by omeprazole of proguanil metabolism: mechanism of the interaction in vitro and prediction of in vivo results from the in vitro experiments. J Pharm Exp Ther 1997; 280: 730–8

    CAS  Google Scholar 

  102. Yu KS, Yim DS, Cho JY, et al. Effect of omeprazole on the pharmacokinetics of moclobemide according to the genetic polymorphism of CYP2C19. Clin Pharmacol Ther 2001; 69: 266–73

    Article  PubMed  CAS  Google Scholar 

  103. Grass U. Drug interactions with proton pump inhibitors: cases reported internationally from medical practice [in German]. Der Kassenarzt 2000; 43: 32–9

    Google Scholar 

  104. Koop H, Bachem MG. Serum iron, ferritin, and vitamin B12 during prolonged omeprazole therapy. J Clin Gastroenterol 1992; 14: 288–92

    Article  PubMed  CAS  Google Scholar 

  105. Reid T, Yuen A, Catolico M, et al. Impact of omeprazole on the plasma clearance of methotrexate. Cancer Chemother Pharmacol 1993; 33: 82–4

    Article  PubMed  CAS  Google Scholar 

  106. Beorlegui B, Aldaz A, Ortega A, et al. Potential interaction between methotrexate and omeprazole. Ann Pharmacother 2000; 34: 1024–7

    Article  PubMed  CAS  Google Scholar 

  107. Bottiger Y, Tybring G, Gotharson E, et al. Inhibition of the sulfoxidation of omeprazole by ketoconazole in poor and extensive metabolizers of S-mephenytoin. Clin Pharmacol Ther 1997; 62: 384–91

    Article  PubMed  CAS  Google Scholar 

  108. Furuta T, Ohashi K, Kobayashi K, et al. Effects of clarithromycin on the metabolism of omeprazole in relation to CYP2C19 genotype status in humans. Clin Pharmacol Ther 1999; 66: 265–74

    Article  PubMed  CAS  Google Scholar 

  109. Cho JY, Yu KS, Jang IJ, et al. Omeprazole hydroxylation is inhibited by a single dose of moclobemide in homozygotic EM genotype for CYP2C19. Br J Clin Pharmacol 2002; 53: 393–7

    Article  PubMed  CAS  Google Scholar 

  110. Yin OQ, Tomlinson B, Waye MM, et al. Pharmacogenetics and herb-drug interactions: experience with Ginkgo biloba and omeprazole. Pharmacogenetics 2004; 14: 841–50

    Article  PubMed  Google Scholar 

  111. Wang LS, Zhou G, Zhu B, et al. St. John’s wort induces both cytochrome P450 3A4-ctalyzed sulfoxidaiton and 2C19-dependent hydroxylation of omeprazole. Clin Pharmacol Ther 2004; 75: 191–7

    Article  PubMed  CAS  Google Scholar 

  112. Yasui-Furukori N, Takahata T, Nakagami T, et al. Different inhibitor effect of fluvoxamine on omeprazole metabolism between CYP 2C19 genotypes. Br J Clin Pharmacol 2004; 57: 487–94

    Article  PubMed  CAS  Google Scholar 

  113. Palovaara S, Tybring G, Laine K. The effect of ethinyloestradiol and levonorgestrel on the CYP2C19-mediated metabolisn of omeprazole in healthy female subjects. Br J Clin Pharmacol 2003; 56: 232–7

    Article  PubMed  CAS  Google Scholar 

  114. Abelo A, Andersson TB, Antonsson M, et al. Steroselective metabolism of omeprazole by human cytochrome P450 enzymes. Drug Metab Dispos 2000, 972

    Google Scholar 

  115. Hassan-lin M, Andersson T, Niazi M, et al. A pharmacokinetic study comparing single and repeated oral doses of 20mg and 40mg omeprazole and its two optical isomers, S-meprazole (esomeprazole) and R-meprazole, in healthy subjects. Eur J Clin Pharmacol 2005; 60: 779–84

    Article  CAS  Google Scholar 

  116. Andersson T, Andren K, Cederberg C, et al. Pharmacokinetics and bioavailability of omeprazole after single and repeated oral administration in healthy subjects. Br J Clin Pharmacol 1990; 29: 557–63

    Article  PubMed  CAS  Google Scholar 

  117. Hassan-lin M, Andersson T, Bredberg E, et al. Pharmacokinetics of esomeprazole after oral and intravenous administration of single and repeated doses to healthy subjects. Eur J Clin Pharmacol 2000; 56: 665–70

    Article  Google Scholar 

  118. Simon WA. Pantoprazole: which cytochrome P450 isoenzymes are involved in its biotransformation? [abstract] Gut 1995; 37: A1177

    Google Scholar 

  119. Meyer UA. Metabolic interactions of the proton-pump inhibitors lansoprazole, omeprazole and pantoprazole with other drugs. Eur J Gastroenterol Hepatol 1996; 8Suppl. 1: 21S–5S

    Article  Google Scholar 

  120. Radhofer-Welte S. Pharmacokinetics and metabolism of the proton pump inhibitor pantoprazole in man. Drugs Today 1999; 35: 765–72

    PubMed  CAS  Google Scholar 

  121. Calabresi L, Pazzucconi F, Ferrara S, et al. Pharmacokinetic interactions between omeprazole/pantoprazole and clarithromycin in health volunteers. Pharmacol Res 2004; 49: 493–9

    Article  PubMed  CAS  Google Scholar 

  122. Ferron GM, Paul JC, Fruncillo RJ, et al. Lack of pharmacokinetic interaction between oral pantoprazole and cisapride in healthy adults. J Clin Pharmacol 1999; 39: 945–50

    Article  PubMed  CAS  Google Scholar 

  123. Troger U, Stotzel B, Martens-Lobenhoffer J, et al. Severe myalgia from an interaction between treatments with pantoprazole and methotrexate. BMJ 2002; 324: 1497

    Article  PubMed  CAS  Google Scholar 

  124. Pearce RE, Rodrigues AD, Goldstein JA, et al. Identification of the human P450 enzymes involved in lansoprazole metabolism. J Pharmacol Exp Ther 1996; 277: 805–16

    PubMed  CAS  Google Scholar 

  125. Landes BD, Petite JP, Flouvat B. Clinical pharmacokinetics of lansoprazole. Clin Pharmacokinet 1995; 28: 458–70

    Article  PubMed  CAS  Google Scholar 

  126. Fuchs W, Sennewald R, Klotz U. Lansoprazole does not affect the bioavailability of oral contraceptives. Br J Clin Pharmacol 1994; 38: 376–80

    Article  PubMed  CAS  Google Scholar 

  127. Kokufu T, Ihara N, Sugioka N, et al. Effects of lansoprazole on pharmacokinetics and metabolism of theophylline. Eur J Clin Pharmacol 1995; 48: 391–5

    Article  PubMed  CAS  Google Scholar 

  128. Takahashi K, Motohashi H, Yonezawa A, et al. Lansoprazoletacrolimus interaction in Japanese transplant recipient with CYP2C19 polymorphism. Ann Pharmacother 2004; 38: 791–4

    Article  PubMed  Google Scholar 

  129. Itagaki F, Homma M, Yuzawa K, et al. Effect of lansoprazole and rabeprazole on tacrolimus pharmacokinetics in healthy volunteers with CYP2C19 mutations. J Pharm Pharmacol 2004; 56: 1055–9

    Article  PubMed  CAS  Google Scholar 

  130. Yasui-Furukori N, Saito M, Uno T, et al. Effects of fluvoxamine on lansoprazole pharmacokinetics in relation to CYP2C19 genotypes. J Clin Pharmacol 2004b; 44: 1223–9

    Article  PubMed  CAS  Google Scholar 

  131. Humphries TJ, Nardi RV, Spera AC, et al. Coadministration of rabeprazole sodium (E3810) and ketoconazole results in a predictable interaction with ketoconazole [abstract]. Gastroenterology 1996; 110: A138

    Google Scholar 

  132. Horai Y, Kimura M, Furuie H, et al. Pharmacodynamic effects and kinetic disposition of rabeprazole in relation to CYP 2C19 genotypes. Aliment Pharmcol Ther 2001; 15: 793–803

    Article  CAS  Google Scholar 

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Acknowledgements

This manuscript has been prepared with funding from unrestricted educational grant from ALTANA Pharma AG. The authors of this manuscript have no direct or indirect financial interest in ALTANA, nor have they received any direct honorarium or payment to undertake this work. As a clinical research organisation undertaking phase I clinical trials, SocraTec R&D has undertaken projects involving products of other pharmaceutical companies that also market proton pump inhibitors. Editorial support was provided by Rx Communications Ltd.

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  1. SocraTec R&D GmbH, Feldbergstrasse 27-29, D1440, Oberursel, Germany

    Henning Blume, Frank Donath, André Warnke & Barbara S. Schug

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  1. Henning Blume
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  2. Frank Donath
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  3. André Warnke
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  4. Barbara S. Schug
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Correspondence to Henning Blume.

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Blume, H., Donath, F., Warnke, A. et al. Pharmacokinetic Drug Interaction Profiles of Proton Pump Inhibitors. Drug-Safety 29, 769–784 (2006). https://doi.org/10.2165/00002018-200629090-00002

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