研究背景：
　　抗生素在住院醫療費用佔有相當高的比例，加上注射型抗生素之價格通常比口服抗生素高出許多，且注射型抗生素的使用時程常影響住院天數的長短。因此在目前醫療資源有限的情形下，若在病患病況穩定時及早由注射型抗生素轉換為口服抗生素，在療效相當的前提下，應能進一步節省醫療花費。

研究目的：
　　本研究評估非複雜性急性腎盂腎炎住院病患及早由注射轉換為口服抗生素，是否可達到相當的臨床效果，並降低住院天數及花費。

研究方法：
　　本研究為回溯性世代觀察研究，以民國九十二年一月一日至九十三年十二月三十一日進入國立成功大學醫學院附設醫院住院的非複雜性急性腎盂腎炎成年女性病患為研究對象。急性腎盂腎炎需符合發燒、腰窩痛和膿尿的診斷標準，並排除其他造成複雜性急性腎盂腎炎的因素。經由病歷審閱之後，將符合收案條件之病患依退燒（體溫< 37.5°C）後48小時內是否由注射轉換為口服抗生素做分組依據—在退燒後48小時內即轉換者，為及早轉換組；退燒後48小時之後始轉換者，為較晚轉換組。

結果：
　　共有40位病患納入分析，其中及早轉換組22人，較晚轉換組18人。二組在臨床治癒率(73% vs. 72%, P > 0.95)和三個月復發率(5% vs. 11%, P = 0.579)並沒有差異。及早轉換組使用注射型抗生素的時間較短(79.0小時vs. 105.5小時，P = 0.032)，住院天數也較短(4.5天vs. 6.0天，P = 0.006)。在費用分析方面，較晚轉換組的住院總金額較高(12,301元 vs. 14,674元, P = 0.025)；抗生素藥費在及早轉換組雖然較低，但二組沒有統計上的差異(2,153元 vs. 3,454元，P = 0.221)。

結論：
　　非複雜性急性腎盂腎炎住院病患及早由注射轉換為口服抗生素治療，可在臨床療效相當的結果下，降低注射抗生素的療程、住院天數及住院花費。

BACKGROUND:
　Antimicrobials make up an important part of hospitalization cost. As healthcare resources remain limited, cost-containment maneuver becomes attractive. Timely switch or sequential from initial intravenous to subsequent oral antibiotic treatment is better tolerated, and results in comparable efficacy and may reduce healthcare cost. However, few studies of early switch therapy focus on acute pyelonephritis.

OBJECTIVE:
　To determine whether early switch from intravenous to oral antibiotic therapy in hospitalized patients with uncomplicated acute pyelonephritis could provide equivalent clinical efficacy, while reducing length of stay and cost.

METHODS:
　Adult patients with discharge diagnosis of acute pyelonephritis admitted to National Cheng-Kung University Hospital between January 2003 and December 2004 were eligible for this retrospective cohort study. Enrolled patients were those with fever, flank pain and pyuria, and without any complicating factors. These patients were categorized according to if the time of switch to oral antibiotic were within 48 hours after afebrile. The primary outcomes were cure rate and recurrence rate. The secondary outcomes were length of stay and cost.

RESULTS:
　Of the 40 patients enrolled, 22 were in the early switch group and 18 in the late switch group. No significant difference was found in clinical cure rate (73% vs. 72%, P > 0.95) and 3-month recurrence rate (5% vs. 11%, P = 0.579) between the two groups. The duration of intravenous therapy were shorter in the early switch group (79.0 hours vs. 105.5 hours, P = 0.032), and they were discharged earlier (4.5 days vs. 6.0 days, P = 0.006). Hospitalization cost was higher in the late switch group (NT$12,301 vs. NT$14,674 P = 0.025). Total antibiotic cost was lower in the early switch group, but the difference was not significant (NT$2,153 vs. NT$3,454, P = 0.221).

CONCLUSIONS:
　Timely switch strategy resulted in reduction of the duration of intravenous antibiotic therapy, length of stay, and hospitalization cost, without compromising clinical outcomes in hospitalized patients with uncomplicated acute pyelonephritis.

1. 中央健康保險局：中華民國九十二年全民健康保險統計。(Accessed July 8, 2005, at http://www.nhi.gov.tw/01intro/statistic/2003statistic/index.htm.)
2. 姚淑惠：健保特約醫事服務機構抗生素處方型態之探討。碩士論文。台南: 國立成功大學臨床藥學研究所；1998。
3. Kunin CM. Urinary tract infections in females. Clin Infect Dis 1994;18(1):1-10; quiz 1-2.
4. Barnett BJ, Stephens DS. Urinary tract infection: an overview. Am J Med Sci 1997;314(4):245-9.
5. Warren JW, Abrutyn E, Hebel JR, Johnson JR, Schaeffer AJ, Stamm WE. Guidelines for antimicrobial treatment of uncomplicated acute bacterial cystitis and acute pyelonephritis in women. Infectious Diseases Society of America (IDSA). Clin Infect Dis 1999;29(4):745-58.
6. Hooton TM, Stamm WE. Diagnosis and treatment of uncomplicated urinary tract infection. Infect Dis Clin North Am 1997;11(3):551-81.
7. Ward TT, Jones SR. Genitourinary tract infections. In: Betts RF, Chapman SW, Penn RL, eds. Reese and Betts’ a practical approach to infectious diseases. 5th ed. Philadelphia: Lippincott Williams & Wilkins; 2003:493-540.
8. Pinson AG, Philbrick JT, Lindbeck GH, Schorling JB. ED management of acute pyelonephritis in women: a cohort study. Am J Emerg Med 1994;12(3):271-8.
9. Safrin S, Siegel D, Black D. Pyelonephritis in adult women: inpatient versus outpatient therapy. Am J Med 1988;85(6):793-8.
10. Foxman B, Klemstine KL, Brown PD. Acute pyelonephritis in US hospitals in 1997: hospitalization and in-hospital mortality. Ann Epidemiol 2003;13(2):144-50.
11. Ki M, Park T, Choi B, Foxman B. The epidemiology of acute pyelonephritis in South Korea, 1997-1999. Am J Epidemiol 2004;160(10):985-93.
12. Stamm WE, Hooton TM. Management of urinary tract infections in adults. N Engl J Med 1993;329(18):1328-34.
13. Ramakrishnan K, Scheid DC. Diagnosis and management of acute pyelonephritis in adults. Am Fam Physician 2005;71(5):933-42.
14. Bergeron MG. Treatment of pyelonephritis in adults. Med Clin North Am 1995;79(3):619-49.
15. Coyle EA, Prince RA. Urinary tract infections and prostatitis. In: Dipiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey LM, eds. Pharmacotherapy: a pathophysiologic approach. 5th ed. New York: McGraw-Hill; 2002:1981-96.
16. Johnson JR, Vincent LM, Wang K, Roberts PL, Stamm WE. Renal ultrasonographic correlates of acute pyelonephritis. Clin Infect Dis 1992;14(1):15-22.
17. Shand DG, Nimmon CC, O'Grady F, Cattell WR. Relation between residual urine volume and response to treatment of urinary infection. Lancet 1970;760(1):1305-6.
18. Sobel JD, Kaye D. Urinary tract infections. In: Mandell GL, Bennett JE, Dolin R, eds. Principles and practice of infectious diseases. 5th ed. New York: Churchill Livingstone; 2000:773-805.
19. Johnson JR. Pyelonephritis. Curr Treat Options Infect Dis 2000;2:33-44.
20. Gupta K, Sahm DF, Mayfield D, Stamm WE. Antimicrobial resistance among uropathogens that cause community-acquired urinary tract infections in women: a nationwide analysis. Clin Infect Dis 2001;33(1):89-94.
21. Infectious Diseases Society of the Republic of China, Medical Foundation in Memory of Dr. Deh-Lin Cheng, Foundation of Professor Wei-Chuan Hsieh for Infectious Diseases Research and Education, Lee CY's Research Foundation for Pediatric Infectious Diseases and Vaccine. Guidelines for antimicrobial therapy of urinary tract infections in Taiwan. J Microbiol Immunol Infect 2000;33(4):271-2.
22. Naber KG, Savov O, Salmen HC. Piperacillin 2 g/tazobactam 0.5 g is as effective as imipenem 0.5 g/cilastatin 0.5 g for the treatment of acute uncomplicated pyelonephritis and complicated urinary tract infections. Int J Antimicrob Agents 2002;19(2):95-103.
23. Tomera KM, Burdmann EA, Reyna OG, et al. Ertapenem versus ceftriaxone followed by appropriate oral therapy for treatment of complicated urinary tract infections in adults: results of a prospective, randomized, double-blind multicenter study. Antimicrob Agents Chemother 2002;46(9):2895-900.
24. Naber KG, Bartnicki A, Bischoff W, et al. Gatifloxacin 200 mg or 400 mg once daily is as effective as ciprofloxacin 500 mg twice daily for the treatment of patients with acute pyelonephritis or complicated urinary tract infections. Int J Antimicrob Agents 2004;23 Suppl 1:S41-53.
25. Bass PF, 3rd, Jarvis JA, Mitchell CK. Urinary tract infections. Prim Care 2003;30(1):41-61, v-vi.
26. Miller O, 2nd, Hemphill RR. Urinary tract infection and pyelonephritis. Emerg Med Clin North Am 2001;19(3):655-74.
27. Stamm WE, McKevitt M, Counts GW. Acute renal infection in women: treatment with trimethoprim-sulfamethoxazole or ampicillin for two or six weeks. A randomized trial. Ann Intern Med 1987;106(3):341-5.
28. Melekos MD, Naber KG. Complicated urinary tract infections. Int J Antimicrob Agents 2000;15(4):247-56.
29. Talan DA, Stamm WE, Hooton TM, et al. Comparison of ciprofloxacin (7 days) and trimethoprim-sulfamethoxazole (14 days) for acute uncomplicated pyelonephritis pyelonephritis in women: a randomized trial. JAMA 2000;283(12):1583-90.
30. Behr MA, Drummond R, Libman MD, Delaney JS, Dylewski JS. Fever duration in hospitalized acute pyelonephritis patients. Am J Med 1996;101(3):277-80.
31. Hooton TM. The current management strategies for community-acquired urinary tract infection. Infect Dis Clin North Am 2003;17(2):303-32.
32. Paskovaty A, Pflomm JM, Myke N, Seo SK. A multidisciplinary approach to antimicrobial stewardship: evolution into the 21st century. Int J Antimicrob Agents 2005;25(1):1-10.
33. Burnakis TG. A cost effective approach to treatment of infection: "switch therapy". Hosp Pharm 1992;27(4):353-4, 60.
34. Gould IM, Jappy B. Trends in hospital antimicrobial prescribing after 9 years of stewardship. J Antimicrob Chemother 2000;45(6):913-7.
35. Rifenberg RP, Paladino JA, Hanson SC, Tuttle JA, Schentag JJ. Benchmark analysis of strategies hospitals use to control antimicrobial expenditures. Am J Health-System Pharm 1993;53:2054-62.
36. Quintiliani R, Cooper BW, Briceland LL, Nightingale CH. Economic impact of streamlining antibiotic administration. Am J Med 1987;82(4A):391-4.
37. Hamilton-Miller JM. Switch therapy: the theory and practice of early change from parenteral to non-parenteral antibiotic administration. Clin Microbiol Infect 1996;2(1):12-9.
38. Nathwani D, Tillotson G, Davey P. Sequential antimicrobial therapy--the role of quinolones. J Antimicrob Chemother 1997;39(4):441-6.
39. Paladino JA. Pharmacoeconomics of antimicrobial therapy. Am J Health Syst Pharm 1999;56(22 Suppl 3):S25-8.
40. Davey P, Nathwani D. Sequential antibiotic therapy: the right patient, the right time and the right outcome. J Infect 1998;37 Suppl 1:37-44.
41. Conly JM, Low DE. Intravenous to oral antimicrobial stepdown therapy: improving the quality of care and reducing costs. Can J Infect Dis 1995;6:3-5A.
42. Ballow CH. Cost considerations in oral antibiotic therapy. Adv Ther 1995;12(4):199-206.
43. Cunha BA. Intravenous-to-oral antibiotic switch therapy. A cost-effective approach. Postgrad Med 1997;101(4):111-2, 5-8, 22-3 passim.
44. Guay DR. Sequential antimicrobial therapy: a realistic approach to cost containment? Pharmacoeconomics 1993;3(5):341-4.
45. Barlow GD, Nathwani D. Sequential antibiotic therapy. Curr Opin Infect Dis 2000;13(6):599-607.
46. MacGowan AP, Bowker KE. Sequential antimicrobial therapy: pharmacokinetic and pharmacodynamic considerations in sequential therapy. J Infect 1998;37 Suppl 1:30-6.
47. Cramer JA, Mattson RH, Prevey ML, Scheyer RD, Ouellette VL. How often is medication taken as prescribed? A novel assessment technique. JAMA 1989;261(22):3273-7.
48. Drew RH. Programs promoting timely sequential antimicrobial therapy: an American perspective. J Infect 1998;37 Suppl 1:3-9.
49. Jewesson P. Cost-effectiveness and value of an IV switch. Pharmacoeconomics 1994;5(Suppl 2):20-6.
50. Lelekis M, Gould IM. Sequential antibiotic therapy for cost containment in the hospital setting: why not? J Hosp Infect 2001;48(4):249-57.
51. Sevinc F, Prins JM, Koopmans RP, et al. Early switch from intravenous to oral antibiotics: guidelines and implementation in a large teaching hospital. J Antimicrob Chemother 1999;43(4):601-6.
52. Cunha BA. Intravenous to oral antibiotic switch therapy. Drugs Today (Barc) 2001;37(5):311-9.
53. Nathwani D. Sequential switch therapy for lower respiratory tract infections: a European perspective. Chest 1998;113(3 Suppl):211S-8S.
54. Rimmer D. Third generation cephalosporins in the parenteral to oral switch. Pharmacoeconomics 1994;5(Suppl 2):27-33.
55. Cairns C. Implementation of sequential therapy programmes--a pharmacist's view. J Infect 1998;37 Suppl 1:55-9.
56. Niederman MS, McCombs JS, Unger AN, Kumar A, Popovian R. The cost of treating community-acquired pneumonia. Clin Ther 1998;20(4):820-37.
57. Ramirez JA. Advances in antibiotic use: switch therapy. Curr Ther Res 1994;55:30-4.
58. Siegel RE, Halpern NA, Almenoff PL, Lee A, Cashin R, Greene JG. A prospective randomized study of inpatient iv. antibiotics for community-acquired pneumonia. The optimal duration of therapy. Chest 1996;110(4):965-71.
59. Omidvari K, de Boisblanc BP, Karam G, Nelson S, Haponik E, Summer W. Early transition to oral antibiotic therapy for community-acquired pneumonia: duration of therapy, clinical outcomes, and cost analysis. Respir Med 1998;92(8):1032-9.
60. Fine MJ, Stone RA, Lave JR, et al. Implementation of an evidence-based guideline to reduce duration of intravenous antibiotic therapy and length of stay for patients hospitalized with community-acquired pneumonia: a randomized controlled trial. Am J Med 2003;115(5):343-51.
61. De Graeve D, Beutels P. Economic aspects of pneumococcal pneumonia: a review of the literature. Pharmacoeconomics 2004;22(11):719-40.
62. Vogel F. Intravenous/oral sequential therapy in patients hospitalised with community-acquired pneumonia: which patients, when and what agents? Drugs 2002;62(2):309-17.
63. Ward G, Jorden RC, Severance HW. Treatment of pyelonephritis in an observation unit. Ann Emerg Med 1991;20(3):258-61.
64. Caceres VM, Stange KC, Kikano GE, Zyzanski SJ. The clinical utility of a day of hospital observation after switching from intravenous to oral antibiotic therapy in the treatment of pyelonephritis. J Fam Pract 1994;39(4):337-9.
65. Bailey RR, Begg EJ, Smith AH, et al. Prospective, randomized, controlled study comparing two dosing regimens of gentamicin/oral ciprofloxacin switch therapy for acute pyelonephritis. Clin Nephrol 1996;46(3):183-6.
66. Sanchez M, Collvinent B, Miro O, et al. Short-term effectiveness of ceftriaxone single dose in the initial treatment of acute uncomplicated pyelonephritis in women. A randomised controlled trial. Emerg Med J 2002;19(1):19-22.
67. Parker SE, Davey PG. Pharmacoeconomics of intravenous drug administration. Pharmacoeconomics 1992;1(2):103-15.
68. Jonsson B, Lindgren B. Five common fallacies in estimating the economic gains of early discharge. Soc Sci Med 1990;14:27-33.
69. Davey P. Cost effectiveness of quinolones in hospitals and the community. Drugs 1999;58 Suppl 2:71-7.
70. Meiland R, Geerlings SE, Hoepelman AI. Management of bacterial urinary tract infections in adult patients with diabetes mellitus. Drugs 2002;62(13):1859-68.
71. Patterson JE, Andriole VT. Bacterial urinary tract infections in diabetes. Infect Dis Clin North Am 1997;11(3):735-50.
72. Parker J, Kunin C. Pyelonephritis in young women. A 10- to 20- year follow-up. JAMA 1973;224(5):585-90.
73. Nicolle LE, Friesen D, Harding GK, Roos LL. Hospitalization for acute pyelonephritis in Manitoba, Canada, during the period from 1989 to 1992; impact of diabetes, pregnancy, and aboriginal origin. Clin Infect Dis 1996;22(6):1051-6.
74. Wullt B, Bergsten G, Fischer H, et al. The host response to urinary tract infection. Infect Dis Clin North Am 2003;17(2):279-301.
75. Bailey RR. Duration of antimicrobial treatment and the use of drug combinations for the treatment of uncomplicated acute pyelonephritis. Infection 1994;22 Suppl 1:S50-2.
76. Meyrier A, Guibert J. Diagnosis and drug treatment of acute pyelonephritis. Drugs 1992;44(3):356-67.
77. Bergeron MG, Marois Y. Benefit from high intrarenal levels of gentamicin in the treatment of E. coli pyelonephritis. Kidney Int 1986;30(4):481-7.
78. Sandberg T, Alestig K, Eilard T, et al. Aminoglycosides do not improve the efficacy of cephalosporins for treatment of acute pyelonephritis in women. Scand J Infect Dis 1997;29(2):175-9.
79. Wechsler A. Pyelonephritis in non-pregnant women. Clin Evid 2004(11):2527-33.
80. Johnson JR, Lyons MF, 2nd, Pearce W, et al. Therapy for women hospitalized with acute pyelonephritis: a randomized trial of ampicillin versus trimethoprim-sulfamethoxazole for 14 days. J Infect Dis 1991;163(2):325-30.
81. Otto G, Sandberg T, Marklund BI, Ulleryd P, Svanborg C. Virulence factors and pap genotype in Escherichia coli isolates from women with acute pyelonephritis, with or without bacteremia. Clin Infect Dis 1993;17(3):448-56.
82. Thanassi M. Utility of urine and blood cultures in pyelonephritis. Acad Emerg Med 1997;4(8):797-800.
83. McMurray BR, Wrenn KD, Wright SW. Usefulness of blood cultures in pyelonephritis. Am J Emerg Med 1997;15(2):137-40.
84. Velasco M, Martinez JA, Moreno-Martinez A, et al. Blood cultures for women with uncomplicated acute pyelonephritis: are they necessary? Clin Infect Dis 2003;37(8):1127-30.
85. Lauderdale TL, Clifford McDonald L, Shiau YR, et al. The status of antimicrobial resistance in Taiwan among gram-negative pathogens: the Taiwan surveillance of antimicrobial resistance (TSAR) program, 2000. Diagn Microbiol Infect Dis 2004;48(3):211-9.
86. Knox K, Lawson W, Dean B, Holmes A. Multidisciplinary antimicrobial management and the role of the infectious diseases pharmacist--a UK perspective. J Hosp Infect 2003;53(2):85-90.
87. Weller TM, Jamieson CE. The expanding role of the antibiotic pharmacist. J Antimicrob Chemother 2004;54(2):295-8.
88. Naranjo CA, Busto U, Sellers EM, et al. A method for estimating the probability of adverse drug reactions. Clin Pharmacol Ther 1981;30(2):239-45.
89. Owens RC, Jr., Ambrose PG. Torsades de pointes associated with fluoroquinolones. Pharmacotherapy 2002;22(5):663-8; discussion 8-72.
90. Frothingham R. Rates of torsades de pointes associated with ciprofloxacin, ofloxacin, levofloxacin, gatifloxacin, and moxifloxacin. Pharmacotherapy 2001;21(12):1468-72.
91. Bertino JS, Jr., Owens RC, Jr., Carnes TD, Iannini PB. Gatifloxacin-associated corrected QT interval prolongation, torsades de pointes, and ventricular fibrillation in patients with known risk factors. Clin Infect Dis 2002;34(6):861-3.
92. Micromedex Healthcare Series. Vol. 124, 2nd Quarter, Apr. 2005
93. Tatro DS, ed. Drug interaction facts. St. Louis: Facts and Comparisons; 2005.
94. Fish DN. Fluoroquinolone adverse effects and drug interactions. Pharmacotherapy 2001;21(10 Pt 2):253S-72S.
95. Shiba K, Sakai O, Shimada J, Okazaki O, Aoki H, Hakusui H. Effects of antacids, ferrous sulfate, and ranitidine on absorption of DR-3355 in humans. Antimicrob Agents Chemother 1992;36(10):2270-4.
96. Shimada J, Shiba K, Oguma T, et al. Effect of antacid on absorption of the quinolone lomefloxacin. Antimicrob Agents Chemother 1992;36(6):1219-24.
97. Balfour JA, Wiseman LR. Moxifloxacin. Drugs 1999;57(3):363-73; discussion 74.
98. Noel GJ, Natarajan J, Chien S, Hunt TL, Goodman DB, Abels R. Effects of three fluoroquinolones on QT interval in healthy adults after single doses. Clin Pharmacol Ther 2003;73(4):292-303.
99. Polk RE, Healy DP, Sahai J, Drwal L, Racht E. Effect of ferrous sulfate and multivitamins with zinc on absorption of ciprofloxacin in normal volunteers. Antimicrob Agents Chemother 1989;33(11):1841-4.
100. Lehto P, Kivisto KT. Different effects of products containing metal ions on the absorption of lomefloxacin. Clin Pharmacol Ther 1994;56(5):477-82.
101. Van Slooten AD, Nix DE, Wilton JH, Love JH, Spivey JM, Goldstein HR. Combined use of ciprofloxacin and sucralfate. Dicp 1991;25(6):578-82.
102. Lee LJ, Hafkin B, Lee ID, Hoh J, Dix R. Effects of food and sucralfate on a single oral dose of 500 milligrams of levofloxacin in healthy subjects. Antimicrob Agents Chemother 1997;41(10):2196-200.
103. Stass H, Schuhly U, Moller JG, Delesen H. Effects of sucralfate on the oral bioavailability of moxifloxacin, a novel 8-methoxyfluoroquinolone, in healthy volunteers. Clin Pharmacokinet 2001;40 Suppl 1:49-55.
104. Davis R, Markham A, Balfour JA. Ciprofloxacin. An updated review of its pharmacology, therapeutic efficacy and tolerability. Drugs 1996;51(6):1019-74.
105. Marchbanks CR. Drug-drug interactions with fluoroquinolones. Pharmacotherapy 1993;13(2 Pt 2):23S-8S.
106. Gisclon LG, Curtin CR, Fowler CL, Williams RR, Hafkin B, Natarajan J. Absence of a pharmacokinetic interaction between intravenous theophylline and orally administered levofloxacin. J Clin Pharmacol 1997;37(8):744-50.
107. Israel DS, Stotka J, Rock W, et al. Effect of ciprofloxacin on the pharmacokinetics and pharmacodynamics of warfarin. Clin Infect Dis 1996;22(2):251-6.
108. Ravnan SL, Locke C. Levofloxacin and warfarin interaction. Pharmacotherapy 2001;21(7):884-5.
109. Gheno G, Cinetto L. Levofloxacin-warfarin interaction. Eur J Clin Pharmacol 2001;57(5):427.
110. Jones CB, Fugate SE. Levofloxacin and warfarin interaction. Ann Pharmacother 2002;36(10):1554-7.
111. Bates DW, Yu DT. Clinical impact of drug-drug interactions with systemic azole antifungals. Drugs Today (Barc) 2003;39(10):801-13.
112. 行政院衛生署。中華民國九十三年六月三日衛署藥字第○九三○三一六五六二號公告：公告含cisapride成分藥品之安全性再評估結果相關事宜。衛生署公報第三十三卷第二十號；2004。
113. 行政院衛生署。中華民國九十四年二月十六日衛署藥字第○九四○三○四六九一號公告：公告terfenadine藥品之安全性評估事宜；2005。
114. Jaruratanasirikul S, Sriwiriyajan S. Effect of omeprazole on the pharmacokinetics of itraconazole. Eur J Clin Pharmacol 1998;54(2):159-61.
115. Chin TW, Loeb M, Fong IW. Effects of an acidic beverage (Coca-Cola) on absorption of ketoconazole. Antimicrob Agents Chemother 1995;39(8):1671-5.
116. Lazar JD, Wilner KD. Drug interactions with fluconazole. Rev Infect Dis 1990;12 Suppl 3:S327-33.
117. Blum RA, Wilton JH, Hilligoss DM, et al. Effect of fluconazole on the disposition of phenytoin. Clin Pharmacol Ther 1991;49(4):420-5.
118. Ducharme MP, Slaughter RL, Warbasse LH, et al. Itraconazole and hydroxyitraconazole serum concentrations are reduced more than tenfold by phenytoin. Clin Pharmacol Ther 1995;58(6):617-24.
119. Apseloff G, Hilligoss DM, Gardner MJ, et al. Induction of fluconazole metabolism by rifampin: in vivo study in humans. J Clin Pharmacol 1991;31(4):358-61.
120. Blomley M, Teare EL, de Belder A, Thway Y, Weston M. Itraconazole and anti-tuberculosis drugs. Lancet 1990;336(8725):1255.
121. Tucker RM, Denning DW, Hanson LH, et al. Interaction of azoles with rifampin, phenytoin, and carbamazepine: in vitro and clinical observations. Clin Infect Dis 1992;14(1):165-74.
122. Engelhard D, Stutman HR, Marks MI. Interaction of ketoconazole with rifampin and isoniazid. N Engl J Med 1984;311(26):1681-3.
123. Meunier F. Serum fungistatic and fungicidal activity in volunteers receiving antifungal agents. Eur J Clin Microbiol 1986;5(1):103-9.
124. Doble N, Shaw R, Rowland-Hill C, Lush M, Warnock DW, Keal EE. Pharmacokinetic study of the interaction between rifampicin and ketoconazole. J Antimicrob Chemother 1988;21(5):633-5.
125. Buggia I, Zecca M, Alessandrino EP, et al. Itraconazole can increase systemic exposure to busulfan in patients given bone marrow transplantation. GITMO (Gruppo Italiano Trapianto di Midollo Osseo). Anticancer Res 1996;16(4A):2083-8.
126. Kantola T, Kivisto KT, Neuvonen PJ. Effect of itraconazole on the pharmacokinetics of atorvastatin. Clin Pharmacol Ther 1998;64(1):58-65.
127. Mazzu AL, Lasseter KC, Shamblen EC, Agarwal V, Lettieri J, Sundaresen P. Itraconazole alters the pharmacokinetics of atorvastatin to a greater extent than either cerivastatin or pravastatin. Clin Pharmacol Ther 2000;68(4):391-400.
128. Kantola T, Backman JT, Niemi M, Kivisto KT, Neuvonen PJ. Effect of fluconazole on plasma fluvastatin and pravastatin concentrations. Eur J Clin Pharmacol 2000;56(3):225-9.
129. Kivisto KT, Kantola T, Neuvonen PJ. Different effects of itraconazole on the pharmacokinetics of fluvastatin and lovastatin. Br J Clin Pharmacol 1998;46(1):49-53.
130. Neuvonen PJ, Kantola T, Kivisto KT. Simvastatin but not pravastatin is very susceptible to interaction with the CYP3A4 inhibitor itraconazole. Clin Pharmacol Ther 1998;63(3):332-41.
131. Romero AJ, Pogamp PL, Nilsson LG, Wood N. Effect of voriconazole on the pharmacokinetics of cyclosporine in renal transplant patients. Clin Pharmacol Ther 2002;71(4):226-34.
132. Back DJ, Tjia JF. Comparative effects of the antimycotic drugs ketoconazole, fluconazole, itraconazole and terbinafine on the metabolism of cyclosporin by human liver microsomes. Br J Clin Pharmacol 1991;32(5):624-6.
133. Floren LC, Bekersky I, Benet LZ, et al. Tacrolimus oral bioavailability doubles with coadministration of ketoconazole. Clin Pharmacol Ther 1997;62(1):41-9.
134. Panel on clinical practices for treatment of HIV infection, Department of Health and Human Service. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. April 7, 2005
135. Cato A, 3rd, Cao G, Hsu A, Cavanaugh J, Leonard J, Granneman R. Evaluation of the effect of fluconazole on the pharmacokinetics of ritonavir. Drug Metab Dispos 1997;25(9):1104-6.
136. Koks CH, Crommentuyn KM, Hoetelmans RM, et al. The effect of fluconazole on ritonavir and saquinavir pharmacokinetics in HIV-1-infected individuals. Br J Clin Pharmacol 2001;51(6):631-5.
137. Grub S, Bryson H, Goggin T, Ludin E, Jorga K. The interaction of saquinavir (soft gelatin capsule) with ketoconazole, erythromycin and rifampicin: comparison of the effect in healthy volunteers and in HIV-infected patients. Eur J Clin Pharmacol 2001;57(2):115-21.
138. Palkama VJ, Isohanni MH, Neuvonen PJ, Olkkola KT. The effect of intravenous and oral fluconazole on the pharmacokinetics and pharmacodynamics of intravenous alfentanil. Anesth Analg 1998;87(1):190-4.
139. Kivisto KT, Lamberg TS, Kantola T, Neuvonen PJ. Plasma buspirone concentrations are greatly increased by erythromycin and itraconazole. Clin Pharmacol Ther 1997;62(3):348-54.
140. Jalava KM, Olkkola KT, Neuvonen PJ. Itraconazole greatly increases plasma concentrations and effects of felodipine. Clin Pharmacol Ther 1997;61(4):410-5.
141. Kaukonen KM, Olkkola KT, Neuvonen PJ. Itraconazole increases plasma concentrations of quinidine. Clin Pharmacol Ther 1997;62(5):510-7.
142. Niemi M, Backman JT, Neuvonen M, Laitila J, Neuvonen PJ, Kivisto KT. Effects of fluconazole and fluvoxamine on the pharmacokinetics and pharmacodynamics of glimepiride. Clin Pharmacol Ther 2001;69(4):194-200.