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Clinical Pharmacokinetics of Clarithromycin

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Abstract

Clarithromycin is a macrolide antibacterial that differs in chemical structure from erythromycin by the methylation of the hydroxyl group at position 6 on the lactone ring. The pharmacokinetic advantages that clarithromycin has over erythromycin include increased oral bioavailability (52 to 55%), increased plasma concentrations (mean maximum concentrations ranged from 1.01 to 1.52 mg/L and 2.41 to 2.85 mg/L after multiple 250 and 500mg doses, respectively), and a longer elimination half-life (3.3 to 4.9 hours) to allow twice daily administration. In addition, clarithromycin has extensive diffusion into saliva, sputum, lung tissue, epithelial lining fluid, alveolar macrophages, neutrophils, tonsils, nasal mucosa and middle ear fluid.

Clarithromycin is primarily metabolised by cytochrome P450 (CYP) 3A isozymes and has an active metabolite, 14-hydroxyclarithromycin. The reported mean values of total body clearance and renal clearance in adults have ranged from 29.2 to 58.1 L/h and 6.7 to 12.8 L/h, respectively. In patients with severe renal impairment, increased plasma concentrations and a prolonged elimination half-life for clarithromycin and its metabolite have been reported. A dosage adjustment for clarithromycin should be considered in patients with a creatinine clearance <1.8 L/h.

The recommended goal for dosage regimens of clarithromycin is to ensure that the time that unbound drug concentrations in the blood remains above the minimum inhibitory concentration is at least 40 to 60% of the dosage interval. However, the concentrations and in vitro activity of 14-hydroxyclarithromycin must be considered for pathogens such as Haemophilus influenzae. In addition, clarithromycin achieves significantly higher drug concentrations in the epithelial lining fluid and alveolar macrophages, the potential sites of extracellular and intracellular respiratory tract pathogens, respectively. Further studies are needed to determine the importance of these concentrations of clarithromycin at the site of infection.

Clarithromycin can increase the steady-state concentrations of drugs that are primarily depend upon CYP3A metabolism (e.g., astemidole, cisapride, pimozide, midazolam and triazolam). This can be clinically important for drugs that have a narrow therapeutic index, such as carbamazepine, cyclosporin, digoxin, theophylline and warfarin. Potent inhibitors of CYP3A (e.g., omeprazole and ritonavir) may also alter the metabolism of clarithromycin and its metabolites. Rifampicin (rifampin) and rifabutin are potent enzyme inducers and several small studies have suggested that these agents may significantly decrease serum clarithromycin concentrations. Overall, the pharmacokinetic and pharmacodynamic studies suggest that fewer serious drug interactions occur with clarithromycin compared with older macrolides such as erythromycin and troleandomycin.

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References

  1. Piscitelli SC, Danziger LH, Rodvold KA. Clarithromycin and azithromycin: new macrolide antibiotics. Clin Pharm 1992; 11: 137–52.

    PubMed  CAS  Google Scholar 

  2. Peters DH, Clissold SP. Clarithromycin: a review of its antimicrobial activity, pharmacokinetic properties, and clinical efficacy. Drugs 1992; 44: 117–64.

    Article  PubMed  CAS  Google Scholar 

  3. Sturgill MG, Rapp RP. Clarithromycin: review of a new macrolide antibiotic with improved microbiologic spectrum and favorable pharmacokinetic and adverse effect profiles. Ann Pharmacother 1992; 26: 1099–108.

    PubMed  CAS  Google Scholar 

  4. Rodvold KA, Piscitelli SC. New oral macrolide and fluoroquinolone antibiotics: an overview of pharmacokinetics, interactions, and safety. Clin Infect Dis 1993; 17 Suppl. 1: S192–9.

    Google Scholar 

  5. Barradell LB, Plosker GL, McTavish D. Clarithromycin: a review of its pharmacological properties and therapeutic use in Mycobacterium avium-intracellulare complex infection in patients with acquired immunodeficiency syndrome. Drugs 1993; 46: 289–312.

    Article  PubMed  CAS  Google Scholar 

  6. Amsden GW. Erythromycin, clarithromycin, and azithromycin: are the differences real? Clin Ther 1996; 18: 56–73.

    Article  PubMed  CAS  Google Scholar 

  7. Langtry HD, Brogden RN. Clarithromycin: a review of its efficacy in the treatment of respiratory tract infections in immunocompetent patients. Drugs 1997; 53: 973–1004.

    Article  PubMed  CAS  Google Scholar 

  8. Davey PG. The pharmacokinetics of clarithromycin and its 14-OH metabolite. J Hosp Infect 1991; 19 Suppl. A: 29–37.

    Article  PubMed  Google Scholar 

  9. Hardy DG, Guay DRP, Jones RN. Clarithromycin, a unique macrolide: a pharmacokinetic, microbiological, and clinical overview. Diagn Microbiol Infect Dis 1992; 15: 39–53.

    Article  PubMed  CAS  Google Scholar 

  10. Fraschini F, Scaglione F, Demartini G. Clarithromycin clinical pharmacokinetics. Clin Pharmacokinet 1993; 25: 189–204.

    Article  PubMed  CAS  Google Scholar 

  11. Guay DRP. Macrolide antibiotics in paediatric infectious diseases. Drugs 1996; 51: 515–36.

    Article  PubMed  CAS  Google Scholar 

  12. Fernandes PB, Ramer N, Rode RA, et al. Bioassay for A-56268 (TE-031) and identification of its major metabolite 14-hydroxy-6-O-methyl erythromycin. Eur J Clin Microbiol Infect Dis 1988; 7: 73–6.

    Article  PubMed  CAS  Google Scholar 

  13. Chu SY, Sennello LT, Sonders RC. Simultaneous determination of clarithromycin and 14(R)-hydroxyclarithromycin in plasma and urine high-performance liquid chromatography with electrochemical detection. J Chromatogr 1991; 571: 199–208.

    Article  PubMed  CAS  Google Scholar 

  14. Hedenmo M, Eriksson BM. Liquid Chromatographic determination of the macrolide antibiotics roxithromycin and clarithromycin in plasma by automated solid-phase extraction and electrochemical detection. J Chromatogr 1995; 692: 161–6.

    Article  CAS  Google Scholar 

  15. Erah PO, Barrett DA, Shaw PN. Ion-pair high-performance liquid Chromatographie assay method for the assessment of clarithromycin stability in aqueous solution and in gastric juice. J Chromatogr B Biomed Appl 1996; 682: 73–8.

    Article  PubMed  CAS  Google Scholar 

  16. Kees F, Spangler S, Wellenhofer M. Determination of macrolides in biological matrices by high-performance liquid chromatography with electrochemical detection. J Chromatogr 1998; 812: 287–93.

    Article  CAS  Google Scholar 

  17. Chu SY, Wilson DS, Deaton RL, et al. Single- and multiple-dose pharmacokinetics of clarithromycin, a new macrolide antimicrobial. J Clin Pharmacol 1993; 33: 719–26.

    PubMed  CAS  Google Scholar 

  18. Chu SY, Granneman GR, Pichotta PJ, et al. Effect of moderate or severe hepatic impairment on clarithromycin pharmacokinetics. J Clin Pharmacol 1993; 33: 480–5.

    PubMed  CAS  Google Scholar 

  19. Kees F, Wellenhofer M, Grobecker H. Serum and cellular pharmacokinetics of clarithromycin 500 mg q.d. and 250 mg b.i.d. in volunteers. Infection 1995; 23: 168–72.

    Article  PubMed  CAS  Google Scholar 

  20. Chu SY, Park Y, Locke C, et al. Drug-food interaction potential of clarithromycin, a new macrolide antimicrobial. J Clin Pharmacol 1992; 32: 32–6.

    PubMed  CAS  Google Scholar 

  21. Chu SY, Wilson DS, Guay DRP, et al. Clarithromycin pharmacokinetics in healthy young and elderly volunteers. J Clin Pharmacol 1992; 32: 1045–9.

    PubMed  CAS  Google Scholar 

  22. Chu SY, Deaton R, Cavanaugh J. Absolute bioavailability of clarithromycin after oral administration in humans. Antimicrob Agents Chemother 1992; 36: 1147–50.

    Article  PubMed  CAS  Google Scholar 

  23. Guay DRP, Craft JC. Overview of the pharmacology of clarithromycin suspension in children and a comparison with that in adults. Pediatr Infect Dis J 1993; 12: S106–11.

    Article  PubMed  CAS  Google Scholar 

  24. Fish DN, Abraham E. Pharmacokinetics of a clarithromycin suspension administered via nasogastric tube to seriously ill patients. Antimicrob Agents Chemother 1999; 43: 1277–80.

    PubMed  CAS  Google Scholar 

  25. Gan VN, Chu SY, Kusmiesz HT, et al. Pharmacokinetics of a clarithromycin suspension in infants and children. Antimicrob Agents Chemother 1992; 36: 2478–80.

    Article  PubMed  CAS  Google Scholar 

  26. Husson RN, Ross LA, Sandelli S, et al. Orally administered clarithromycin for the treatment of systemic Mycobacterium avium complex infection in children with acquired immunodeficiency syndrome. J Pediatr 1994; 124: 807–14.

    Article  PubMed  CAS  Google Scholar 

  27. Ishiguro M, Koga H, Kohno S, et al. Penetration of macrolides into human polymorphonuclear leucocytes. J Antimicrob Chemother 1989; 24: 719–29.

    Article  PubMed  CAS  Google Scholar 

  28. Fietta A, Merlini C, Grassi GG. Requirements for intracellular accumulation and release of clarithromycin and azithromycin by human phagocytes. J Chemother 1997; 9: 23–31.

    PubMed  CAS  Google Scholar 

  29. Wust J, Hardegger U. Penetration of clarithromycin into human saliva. Chemotherapy 1993; 39: 293–6.

    Article  PubMed  CAS  Google Scholar 

  30. Scaglione F, Pintucci JP, Tassi GF, et al. Penetration of clarithromycin into oral and respiratory tissues. Drug Invest 1993; 6: 104–9.

    Google Scholar 

  31. Tsang KWT, Roberts P, Read RC, et al. The concentration of clarithromycin and its 14-hydroxy metabolite in sputum of patients with bronchiectasis following single dose oral administration. J Antimicrob Chemother 1994; 33: 289–97.

    Article  PubMed  CAS  Google Scholar 

  32. Fish DN, Gotfried MH, Danziger LH, et al. Penetration of clarithromycin into lung tissues from patients undergoing lung resection. Antimicrob Agents Chemother 1994; 38: 876–8.

    Article  PubMed  CAS  Google Scholar 

  33. Sundberg L, Cederberg A. Penetration of clarithromycin and its 14-hydroxy metabolite into middle ear effusion in children with secretory otitis media. J Antimicrob Chemother 1994; 33: 299–307.

    Article  PubMed  CAS  Google Scholar 

  34. Gan VN, McCarty JM, Chu SY, et al. Penetration of clarithromycin into middle ear fluid of children with acute otitis media. Pediatr Infect Dis J 1997; 16: 39–43.

    Article  PubMed  CAS  Google Scholar 

  35. Conte JE, Golden J, Duncan S, et al. Single-dose intrapulmonary pharmacokinetics of azithromycin, clarithromycin, ciprofloxacin, and cefuroxime in volunteer subjects. Antimicrob Agents Chemother 1996; 40: 1617–22.

    PubMed  CAS  Google Scholar 

  36. Honeybourne D, Kees F, Andrews JM, et al. The levels of clarithromycin and its 14-hydroxy metabolite in the lung. Eur Respir J 1994; 7: 1275–80.

    Article  PubMed  CAS  Google Scholar 

  37. Conte JE, Golden J, Duncan S, et al. Intrapulmonary pharmacokinetics of clarithromycin and erythromycin. Antimicrob Agents Chemother 1996; 40: 1617–22.

    PubMed  CAS  Google Scholar 

  38. Patel KB, Xuan D, Tessier PR, et al. Comparison of bronchopulmonary pharmacokinetics of clarithromycin and azithromycin. Antimicrob Agents Chemother 1996; 40: 2375–9.

    PubMed  CAS  Google Scholar 

  39. Rodvold KA, Gotfried MH, Danziger LH, et al. Intrapulmonary steady-state concentrations of clarithromycin and azithromycin in healthy adult volunteers. Antimicrob Agents Chemother 1997; 41: 1399–402.

    PubMed  CAS  Google Scholar 

  40. Ferrero JL, Bopp BA, March KC, et al. Metabolism and disposition of clarithromycin in man. Drug Metab Dispos 1990; 18: 441–6.

    PubMed  CAS  Google Scholar 

  41. Rodrigues AD, Roberts EM, Mulford DJ, et al. Oxidative metabolism of clarithromycin in the presence of human liver microsomes. Major role for the cytochrome P4503A (CYP3A) subfamily. Drug Metab Dispos 1997; 25: 623–30.

    PubMed  CAS  Google Scholar 

  42. Chu SY, Sennello LT, Bunnell ST, et al. Pharmacokinetics of clarithromycin, a macrolide, after single ascending oral doses. Antimicrob Agents Chemother 1992; 36: 2447–53.

    Article  PubMed  CAS  Google Scholar 

  43. Craig WA. Pharmacokinetic/pharmacodynamic parameters: rationale for antibacterial dosing of mice and men. Clin Infect Dis 1998; 26: 1–12.

    Article  PubMed  CAS  Google Scholar 

  44. Craig WA. Postantibiotic effects and the dosing of macrolides, azalides and streptogramins. In: Zinner SH, Young LS, Acar JF, et al., editors. Expanding indications for the new macrolides, azalides and streptogramins. New York: Marcel Dekker Inc, 1997: 27–38.

    Google Scholar 

  45. Hardy DJ, Swanson RN, Rode RA, et al. Enhancement of the in vitro and in vivo activities of clarithromycin against Haemophilus influenzae by 14-hydroxy-clarithromycin, its major metabolite in humans. Antimicrob Agents Chemother 1990; 34: 1407–13.

    Article  PubMed  CAS  Google Scholar 

  46. Jorgensen JH, Maher LA, Howell AW. Activity of clarithromycin and its principal metabolite against Haemophilus influenzae. Antimicrob Agents Chemother 1991; 35: 1524–6.

    Article  PubMed  CAS  Google Scholar 

  47. Amsden GW. Pneumococcal macrolide resistance: myth or reality? J Antimicrob Chemother 1999; 44: 1–6.

    Article  PubMed  CAS  Google Scholar 

  48. Tinel M, Descatoire V, Larrey D, et al. Effects of clarithromycin on cytochrome P-450: comparison with other macrolides. J Pharmacol Exp Ther 1989; 250: 746–51.

    PubMed  CAS  Google Scholar 

  49. Ohmori S, Ishii I, Kuriya SI, et al. Effects of clarithromycin and its metabolites on the mixed function oxidase system in hepatic microsomes of rats. Drug Metab Disp 1993; 21: 358–63.

    CAS  Google Scholar 

  50. Ludden TM. Pharmacokinetic interactions of macrolide antibiotics. Clin Pharmacokinet 1985; 10: 63–79.

    Article  PubMed  CAS  Google Scholar 

  51. Periti P, Mazzei T, Mini E, et al. Pharmacokinetic drug interactions of macrolides. Clin Pharmacokinet 1992; 23: 106–31.

    Article  PubMed  CAS  Google Scholar 

  52. von Rosenstiel NA, Adam D. Macrolide antibacterials: drug interactions of clinical significance. Drug Saf 1995; 13: 105–22.

    Article  Google Scholar 

  53. Amsden GW. Macrolide versus azalides: a drug interaction update. Ann Pharmacother 1995; 29: 906–17.

    PubMed  CAS  Google Scholar 

  54. Nahata M. Drug interactions with azithromycin and the macrolides: an overview. J Antimicrob Chemother 1996; 37 Suppl. C: 133–42.

    Article  PubMed  CAS  Google Scholar 

  55. Watkins VS, Polk RE, Stotka JL. Drug interactions of macrolides: emphasis on dirithromycin. Ann Pharmacother 1997; 31: 349–56.

    PubMed  CAS  Google Scholar 

  56. Zundorf H, Wischmann L, Fassbender M, et al. Pharmacokinetics of clarithromycin and possible interaction with H2 blockers and antacids [abstract no. 515]. In: Program and Abstracts of the 31st Interscience Conference on Antimicrobial Agents and Chemotherapy; 1991 Sep 29–Oct 21; Chicago (IL). Washington, DC: American Society for Microbiology, 1991: 185.

    Google Scholar 

  57. Yasui N, Otani K, Kaneko S, et al. Carbamazepine toxicity induced by clarithromycin coadministration in psychiatric patients. Int Clin Psychopharmacol 1997; 12: 225–9.

    Article  PubMed  CAS  Google Scholar 

  58. Metz DC, Getz HD. Helicobacter pylori gastritis therapy with omeprazole and clarithromycin increases serum carbamazepine levels. Dig Dis Sci 1995; 40: 912–4.

    Article  PubMed  CAS  Google Scholar 

  59. Albani F, Riva R, Baruzzi A. Clarithromycin-carbamazepine interaction: a case report. Epilepsia 1993; 34: 161–2.

    Article  PubMed  CAS  Google Scholar 

  60. Richens A, Chu SY, Sennello LT, et al. Effect of multiple doses of clarithromycin on the pharmacokinetics of carbamazepine [abstract no. 760]. In: Program and Abstracts of the 30th Inter-science Conference on Antimicrobial Agents and Chemotherapy; 1990 Oct 21–24; Atlanta (GA). Washington, DC: American Society for Microbiology, 1990: 213.

    Google Scholar 

  61. Amsden GW, Cheng KL, Peloquin CA, et al. Oral cimetidine prolongs clarithromycin absorption. Antimicrob Agents Chemother 1998; 42: 1578–80.

    PubMed  CAS  Google Scholar 

  62. van Haarst AD, van’t Klooster GAE, van Gerven JMA, et al. The influence of cisapride and clarithromycin on QT intervals in healthy volunteers. Clin Pharmacol Ther 1998; 64: 542–6.

    Article  PubMed  Google Scholar 

  63. Sekkarie MA. Torsades de pointes in two chronic renal failure patients treated with cisapride and clarithromycin. Am J Kidney Dis 1997; 30: 437–9.

    Article  PubMed  CAS  Google Scholar 

  64. Piquette RK. Torsade de pointes induced by cisapride/clarithromycin interaction. Ann Pharmacother 1999; 33: 22–6.

    Article  PubMed  CAS  Google Scholar 

  65. Sadaba B, Lopez de Ocariz A, Azanaz JR, et al. Concurrent clarithromycin and cyclosporin A treatment. J Antimicrob Chemother 1998; 42: 393–5.

    Article  PubMed  CAS  Google Scholar 

  66. Spicer ST, Liddle C, Chapman JR, et al. The mechanism of cyclosporine toxicity induced by clarithromycin. Br J Clin Pharmacol 1997; 43: 194–6.

    Article  PubMed  CAS  Google Scholar 

  67. Sketris IS, Wright MR, West ML. Possible role of the intestinal P-450 enzyme system in a cyclosporine-clarithromycin interaction. Pharmacotherapy 1996; 16: 301–5.

    PubMed  CAS  Google Scholar 

  68. Ferrari SL, Goffin E, Mourad M, et al. The interaction between clarithromycin and cyclosporine in kidney transplant recipients. Transplantation 1994; 58: 725–7.

    PubMed  CAS  Google Scholar 

  69. Gersema LM, Porter CB, Russell EH. Suspected drug interaction between cyclosporine and clarithromycin [letter]. J Heart Lung Transplant 1994; 13: 343–5.

    PubMed  CAS  Google Scholar 

  70. Gillum JG, Bruzzese VL, Israel DS, et al. Effect of clarithromycin on the pharmacokinetics of 2′,3′-dideoxyinosine in patients who are seropositive for human immunodeficiency virus. Clin Infect Dis 1996; 22: 716–8.

    Article  PubMed  CAS  Google Scholar 

  71. Wakasugi H, Yano I, Ito T, et al. Effect of clarithromycin on renal excretion of digoxin: interaction with P-glycoprotein. Clin Pharmacol Ther 1998; 64: 123–8.

    Article  PubMed  CAS  Google Scholar 

  72. Trivedi S, Hyman J, Lichstein E. Clarithromycin and digoxin toxicity [letter]. Ann Intern Med 1998; 128: 604.

    PubMed  CAS  Google Scholar 

  73. Guerriero SE, Ehrenpreis E, Gallagher KL. Two cases of clarithromycin-induced digoxin toxicity. Pharmacotherapy 1997; 17: 1035–7.

    PubMed  CAS  Google Scholar 

  74. Laberge P, Martineau P. Clarithromycin-induced digoxin intoxication. Ann Pharmacother 1997; 31: 999–1002.

    PubMed  CAS  Google Scholar 

  75. Nawarskas JJ, McCarthy DM, Spinler SA. Digoxin toxicity secondary to clarithromycin therapy. Ann Pharmacother 1997; 31: 864–6.

    PubMed  CAS  Google Scholar 

  76. Brown BA, Wallace RJ, Griffith DE, et al. Clarithromycin-associated digoxin toxicity in the elderly. Clin Infect Dis 1997; 24: 92–3.

    Article  PubMed  CAS  Google Scholar 

  77. Ford A, Smith LC, Baltch AL, et al. Clarithromycin-induced digoxin toxicity in a patient with AIDS. Clin Infect Dis 1995; 21: 1051–2.

    Article  PubMed  CAS  Google Scholar 

  78. Midoneck SR, Etingin OR. Clarithromycin-related toxic effects of digoxin [letter]. N Engl J Med 1995; 333: 1505.

    Article  PubMed  CAS  Google Scholar 

  79. Paar D, Terjung B, Sauerbruch T. Life-threatening interaction between clarithromycin and disopyramide. Lancet 1997; 349: 326–7.

    Article  PubMed  CAS  Google Scholar 

  80. Gustavson LE, Shi H, Palmer RN, et al. Drug interaction between clarithromycin and fluconazole in healthy subjects [abstract PII-107]. Clin Pharmacol Ther 1996; 59: 185.

    Article  Google Scholar 

  81. Cheng KL, Nafziger AN, Peloquin CA, et al. Effect of grapefruit juice on clarithromycin pharmacokinetics. Antimicrob Agents Chemother 1998; 42: 927–9.

    PubMed  CAS  Google Scholar 

  82. Carr RA, Edmonds A, Shi H, et al. Steady-state pharmacokinetics and electrocardiographic pharmacodynamics of clarithromycin and loratadine after individual or concomitant administration. Antimicrob Agents Chemother 1998; 42: 1176–80.

    PubMed  CAS  Google Scholar 

  83. Fost DA, Leung DYM, Martin RJ, et al. Inhibition of methylprednisolone elimination in the presence of clarithromycin therapy. J Allergy Clin Immunol 1999; 103: 1031–5.

    Article  PubMed  CAS  Google Scholar 

  84. Gorski JC, Jones DR, Haehner-Daniels BD, et al. The contribution of intestinal and hepatic CYP3A to the interaction between midazolam and clarithromycin. Clin Pharmacol Ther 1998; 64: 133–43.

    Article  PubMed  CAS  Google Scholar 

  85. Yeates RA, Laufen H, Zimmeran T, et al. Pharmacokinetic and pharmacodynamic interaction study between midazolam and macrolide antibiotics, erythromycin, clarithromycin, and azithromycin. Int J Clin Pharmacol Ther 1997; 35: 577–9.

    PubMed  CAS  Google Scholar 

  86. Yeates RA, Laufen H, Zimmeran T. Interaction between midazolam and clarithromycin: comparison with azithromycin. Int J Clin Pharmacol Ther 1996; 34: 400–5.

    PubMed  CAS  Google Scholar 

  87. Gustavson LE, Kaiser JF, Edmonds AL, et al. Effect of omeprazole on concentrations of clarithromycin in plasma and gastric tissue at steady state. Antimicrob Agents Chemother 1995; 39: 2078–83.

    Article  PubMed  CAS  Google Scholar 

  88. Goddard AF, Jessa MJ, Barrett DA, et al. Effect of omeprazole on the distribution of metronidazole, amoxicillin, and clarithromycin in human gastric juice. Gastroenterology 1996; 111: 358–67.

    Article  PubMed  CAS  Google Scholar 

  89. Desta Z, Kerbusch T, Flockhart DA. Effect of clarithromycin on the pharmacokinetics and pharmacodynamics of pimozide in healthy poor and extensive metabolizers of cytochrome P450 2D6 (CYP2D6). Clin Pharmacol Ther 1999; 65: 10–20.

    Article  PubMed  CAS  Google Scholar 

  90. Garey KW, Peloquin CA, Godo PG, et al. Lack of effect of zafirlukast on the pharmacokinetics of azithromycin, clarithromycin, and 14-hydroxyclarithromycin in healthy volunteers. Antimicrob Agents Chemother 1999; 43: 1152–5.

    PubMed  CAS  Google Scholar 

  91. Finkenbine R, Gill HS. Case of mania due to prednisone-clarithromycin interaction [letter]. Can J Psychiatry 1997; 42: 778.

    PubMed  CAS  Google Scholar 

  92. Bennett JE, Wakefield JC, Lacey LF. Modeling of trough plasma bismuth concentrations. J Pharmacokinet Biopharm 1997; 25: 79–106.

    PubMed  CAS  Google Scholar 

  93. Lacey LF, Lettis S, Douglas J, et al. Effect on trough plasma concentrations in duodenal ulcer patients co-prescription of ranitidine bismuth citrate (GR122311X) with clarithromycin or amoxycillin [abstract PPDM-8272]. Pharm Res 1995; 12 Suppl. 1: S394.

    Google Scholar 

  94. Gatti G, Papa P, Torre D, et al. Population pharmacokinetics of rifabutin in human immunodeficiency virus-infected patients. Antimicrob Agents Chemother 1998; 42: 2017–23.

    PubMed  CAS  Google Scholar 

  95. Hafner R, Bethel J, Power M, et al. Tolerance and pharmacokinetic interaction of rifabutin and clarithromycin in human immunodeficiency virus-infected volunteers. Antimicrob Agents Chemother 1998; 42: 631–9.

    PubMed  CAS  Google Scholar 

  96. Apseloff G, Foulds G, LaBoy-Goral L, et al. Comparison of azithromycin and clarithromycin in their interactions with rifabutin in healthy volunteers. J Clin Pharmacol 1998; 38: 830–5.

    PubMed  CAS  Google Scholar 

  97. Iatsimirskaia E, Tulebaev S, Storozhuk E, et al. Metabolism of rifabutin in human enterocyte and liver microsomes: kinetic parameters, identification of enzyme systems, and drug interactions with macrolides and antifungal agents. Clin Pharmacol Ther 1997; 61: 554–62.

    Article  PubMed  CAS  Google Scholar 

  98. Wallace RJ, Brown BA, Griffith DE, et al. Reduced serum levels of clarithromycin in patients with multidrug regimens including rifampin and rifabutin in Mycobacterium avium-M. intracellulare infection. Clin Infect Dis 1995; 171: 747–50.

    Google Scholar 

  99. Peloquin CA, Berning SE. Evaluation of the drug interaction between clarithromycin and rifampin. J Infect Dis Pharmacother 1996; 2: 19–35.

    Article  CAS  Google Scholar 

  100. Ouellet D, Hsu A, Granneman GR, et al. Pharmacokinetic interaction between ritonavir and clarithromycin. Clin Pharmacol Ther 1998; 64: 355–62.

    Article  PubMed  CAS  Google Scholar 

  101. Wolter K, Wagner K, Phillip T, et al. Interaction between FK506 and clarithromycin in a renal transplant patient [letter]. Eur J Clin Pharmacol 1994; 47: 207–8.

    PubMed  CAS  Google Scholar 

  102. Honig PK, Wortham DC, Zamani K, et al. Comparison of the effect of the macrolide antibiotics erythromycin, clarithromycin, and azithromycin on terfenadine steady-state pharmacokinetics and electrocardiographic parameters. Drug Invest 1994; 7: 148–56.

    CAS  Google Scholar 

  103. Jurima-Romet M, Crawford K, Cyr T, et al. Terfenadine metabolism in human liver: in vitro inhibition by macrolide antibiotics and azole antifungals. Drug Metab Dispos 1994; 22: 849–57.

    PubMed  CAS  Google Scholar 

  104. Ruff F, Chu SY, Sonders RC, et al. Effect of multiple doses of clarithromycin on the pharmacokinetics of theophylline [abstract no. 761]. In: Program and Abstracts of the 30th Inter-science Conference on Antimicrobial Agents and Chemotherapy; 1990 Oct 21–24; Atlanta (GA). Washington, DC: American Society for Microbiology, 1990: 213.

    Google Scholar 

  105. Gillum JG, Israel DS, Scott RB, et al. Effect of combination therapy with ciprofloxacin and clarithromycin on theophylline pharmacokinetics in healthy volunteers. Antimicrob Agents Chemother 1996; 40: 1715–6.

    PubMed  CAS  Google Scholar 

  106. Greenblatt DJ, von Moltke LL, Harmatz JS, et al. Inhibition of triazolam clearance by macrolide antimicrobial agents: in vitro correlates and dynamic consequences. Clin Pharmacol Ther 1998; 64: 278–85.

    Article  PubMed  CAS  Google Scholar 

  107. Recker MW, Kier KL. Potential interaction between clarithromycin and warfarin. Ann Pharmacother 1997; 31: 996–8.

    PubMed  CAS  Google Scholar 

  108. Grau E, Esperanza R, Pastor E. Interaction between clarithromycin and oral anticoagulants [letter]. Ann Pharmacother 1996; 30: 1495–6.

    PubMed  CAS  Google Scholar 

  109. Polis MA, Piscitelli SC, Vogel S, et al. Clarithromycin lowers plasma zidovudine levels in persons with human immunodeficiency virus infection. Antimicrob Agents Chemother 1997; 41: 1709–14.

    PubMed  CAS  Google Scholar 

  110. Vance E, Watson-Bitar M, Gustavson L, et al. Pharmacokinetics of clarithromycin and zidovudine in patients with AIDS. Antimicrob Agents Chemother 1995; 39: 1355–60.

    Article  PubMed  CAS  Google Scholar 

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Rodvold, K.A. Clinical Pharmacokinetics of Clarithromycin. Clin Pharmacokinet 37, 385–398 (1999). https://doi.org/10.2165/00003088-199937050-00003

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