ALTERATION IN THE PHARMACOKINETIC DISPOSITION OF CIPROFLOXACIN BY SIMULTANEOUS ADMINISTRATION OF AZLOCILLIN

被引:19
作者
BARRIERE, SL
CATLIN, DH
ORLANDO, PL
NOE, A
FROST, RW
机构
[1] UNIV CALIF LOS ANGELES,DEPT MED,LOS ANGELES,CA 90024
[2] UNIV CALIF LOS ANGELES,DEPT PHARMACOL,LOS ANGELES,CA 90024
[3] UNIV CALIF LOS ANGELES,CTR HLTH SCI,LOS ANGELES,CA 90024
[4] MILES PHARMACEUT INC,DEPT CLIN RES,W HAVEN,CT 06516
关键词
D O I
10.1128/AAC.34.5.823
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
Healthy subjects were given single intravenous doses of ciprofloxacin, azlocillin, and the two drugs simultaneously on separate occasions. High-pressure liquid chromatographic analysis was used to assay the concentrations of both drugs in serum and urine. Pharmacokinetic parameters were calculated by noncompartmental methods. The total body (CL), renal (CL(R)), and nonrenal (CL(NR)) clearances; steady-state volume of distribution (V(ss)); and fractional urinary excretion of ciprofloxacin were all markedly decreased with the simultaneous administration of azlocillin. The disposition of azlocillin was unchanged when it was given with ciprofloxacin to when it was given alone. The pharmacokinetic parameters (mean ± standard deviation) of ciprofloxacin given alone versus in combination with azlocillin were as follows: CL, 52.2 ± 9.2 versus 33.9 ± 6.0 liters/h (P < 0.0005); CL(R), 26.5 ± 4.8 versus 16.2 ± 4.2 liters/h (P < 0.0005); CL(NR), 25.8 ± 5.5 versus 17.7 ± 4.0 liters/h (P < 0.03); V(ss), 224 ± 30 versus 166 ± 42 liters (P < 0.01); fractional urinary excretion, 0.56 ± 0.06 versus 0.43 ± 0.04 (P < 0.002), respectively. This interaction resulted in significantly higher and more prolonged concentrations of ciprofloxacin in serum, which may be beneficial in the treatment of serious gram-negative bacterial infections, but it could also produce greater toxicity or result in more pronounced effects on oxidative drug metabolism of other medications.
引用
收藏
页码:823 / 826
页数:4
相关论文
共 11 条
  • [1] CIPROFLOXACIN, AZLOCILLIN, CEFTIZOXIME AND AMIKACIN ALONE AND IN COMBINATION AGAINST GRAM-NEGATIVE BACILLI IN AN INFECTED CHAMBER MODEL
    BAMBERGER, DM
    PETERSON, LR
    GERDING, DN
    MOODY, JA
    FASCHING, CE
    [J]. JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY, 1986, 18 (01) : 51 - 63
  • [2] DRUSANO GL, 1984, REV INFECT DIS, V6, P13
  • [3] COMPARATIVE EFFICACY OF CIPROFLOXACIN, AZLOCILLIN, AND TOBRAMYCIN ALONE AND IN COMBINATION IN EXPERIMENTAL PSEUDOMONAS SEPSIS
    JOHNSON, M
    MINITER, P
    ANDRIOLE, VT
    [J]. JOURNAL OF INFECTIOUS DISEASES, 1987, 155 (04) : 783 - 788
  • [4] JUSKO WJ, 1989, APPLIED PHARMACOKINE, P9
  • [5] KINETIC INTERACTIONS BETWEEN AZLOCILLIN, CEFOTAXIME, AND CEFOTAXIME METABOLITES IN NORMAL AND IMPAIRED RENAL-FUNCTION
    KAMPF, D
    BORNER, K
    MOLLER, M
    KESSEL, M
    [J]. CLINICAL PHARMACOLOGY & THERAPEUTICS, 1984, 35 (02) : 214 - 220
  • [6] LIQUID-CHROMATOGRAPHIC ANALYSIS OF CIPROFLOXACIN AND CIPROFLOXACIN METABOLITES IN BODY-FLUIDS
    KROL, GJ
    NOE, AJ
    BEERMANN, D
    [J]. JOURNAL OF LIQUID CHROMATOGRAPHY, 1986, 9 (13): : 2897 - 2919
  • [7] LEBEL M, 1988, PHARMACOTHERAPY, V8, P3
  • [8] INVIVO AND INVITRO ACTIVITY OF CIPROFLOXACIN PLUS AZLOCILLIN AGAINST 12 STREPTOCOCCAL ISOLATES IN A NEUTROPENIC SITE MODEL
    PETERSON, LR
    MOODY, JA
    FASCHING, CE
    GERDING, DN
    [J]. DIAGNOSTIC MICROBIOLOGY AND INFECTIOUS DISEASE, 1987, 7 (02) : 127 - 136
  • [9] INFLUENCE OF COADMINISTRATION ON THE PHARMACOKINETICS OF MEZLOCILLIN AND CEFOTAXIME IN HEALTHY-VOLUNTEERS AND IN PATIENTS WITH RENAL-FAILURE
    RODONDI, LC
    FLAHERTY, JF
    SCHOENFELD, P
    BARRIERE, SL
    GAMBERTOGLIO, JG
    [J]. CLINICAL PHARMACOLOGY & THERAPEUTICS, 1989, 45 (05) : 527 - 534
  • [10] PHARMACOKINETICS OF CIPROFLOXACIN IN HEALTHY-VOLUNTEERS AND PATIENTS WITH IMPAIRED KIDNEY-FUNCTION
    WEBB, DB
    ROBERTS, DE
    WILLIAMS, JD
    ASSCHER, AW
    [J]. JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY, 1986, 18 : 83 - 87