Multiple-dose pharmacokinetics of concurrent oral ciprofloxacin and rifampin therapy in elderly patients

Chandler, M. H. H.; Toler, Steven M.; Rapp, Robert P.; Muder, Robert R.; Korvick, Joyce A.

doi:10.1128/aac.34.3.442

Cited by 35 publications

(12 citation statements)

References 27 publications

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“…The pharmacokinetics of ciprofloxacin in elderly individuals have been reported previously (6,13,16). The somewhat lower mean peak concentration in serum, elimination half-life, and AUC in our subjects probably are explained by their somewhat younger age, better renal function, and generally better state of health than those of the elderly hospitalized or institutionalized individuals studied previously (6, 13, 16).…”

Section: Discussionmentioning

confidence: 38%

“…The somewhat lower mean peak concentration in serum, elimination half-life, and AUC in our subjects probably are explained by their somewhat younger age, better renal function, and generally better state of health than those of the elderly hospitalized or institutionalized individuals studied previously (6, 13, 16). Chandler et al (6) recently reported that coadministration of rifampin in doses of 300 mg orally every 12 h with ciprofloxacin had no effect on ciprofloxacin pharmacokinetics. Using a different rifampin dosing regimen, we also observed no statistically significant alterations in ciprofloxacin pharmacokinetics during coadministration of the two drugs.…”

Section: Discussionmentioning

confidence: 99%

“…Although several studies have measured the serum bactericidal activity (SBA) of ciprofloxacin in humans (3,5,12,30,33), only one study (27) has assessed its SBA in a predominantly elderly population, and that study assessed the SBA only against Pseudomonas aeruginosa in a series of patients with malignant otitis externa. Since elderly individuals may be prime candidates for oral therapy with ciprofloxacin and since combination therapy has been suggested both to enhance the antibacterial spectrum of ciprofloxacin (6,19,24,33) and to reduce the potential development of resistance (10,18,19,25,27), we studied the pharmacokinetics of oral ciprofloxacin administered alone and in combination with rifampin or clindamycin in six healthy elderly volunteers and measured its SBA against a broad group of gram-positive and gram-negative pathogens.…”

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confidence: 99%

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Crossover assessment of serum bactericidal activity and pharmacokinetics of ciprofloxacin alone and in combination in healthy elderly volunteers

Weinstein¹,

Deeter²,

Swanson³

et al. 1991

Antimicrob Agents Chemother

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To better define the pharmacokinetics and serum bactericidal activity (SBA) of ciprofloxacin and other antimicrobial agents in the elderly, six healthy elderly (>65 years) volunteers with normal renal function were given ciprofloxacin alone orally, ciprofloxacin plus rifampin orally, ciprofloxacin plus clindamycin orally, rifampin alone orally (three volunteers), and, for comparison of SBA against gram-positive cocci, vancomycin intravenously. Mean peak ciprofloxacin concentrations and other pharmacokinetic parameters were not altered significantly by coadministration of either rifampin or clindamycin. Ciprofloxacin had somewhat greater SBA against the oxacillin-susceptible and oxacillin-resistant Staphylococcus aureus strains tested than did vancomycin, but rifampin was by far the most active single agent tested. The SBA of rifampin against S. aureus was modestly antagonized during combination therapy with ciprofloxacin, but substantial SBA still was present. The ciprofloxacin SBA against S. aureus was completely antagonized by clindamycin if the strains were susceptible to the latter agent. Ciprofloxacin had modest SBA against group A streptococci and no SBA against the three pneumococcal strains tested. All of the regimens had poor to absent SBA against Enterococcus faecalis. By contrast, ciprofloxacin had excellent SBA against Escherichia coli and Klebsiella pneumoniae and moderate SBA against Pseudomonas aeruginosa. Combination therapy with rifampin or clindamycin in general enhanced the SBA against the nonenterococcal streptococci and had no effect on the SBA against the gram-negative bacilli.

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Section: Discussionmentioning

confidence: 38%

Section: Discussionmentioning

confidence: 99%

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confidence: 99%

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Crossover assessment of serum bactericidal activity and pharmacokinetics of ciprofloxacin alone and in combination in healthy elderly volunteers

Weinstein¹,

Deeter²,

Swanson³

et al. 1991

Antimicrob Agents Chemother

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“…C max in adults with tuberculosis treated with 300 mg rifampin once daily is approximately 6.6 (range 2.9 -14) µg/mL [12]. In six elderly male nursing home residents who received 300 mg rifampin orally every 12 hours for 14 days (in addition to ciprofloxacin), C max after dose 12 and 27 were 9.4 ± 3.1 and 7.3 ± 2.3 µg/mL, respectively [13]. Rifampin M A N U S C R I P T A C C E P T E D ACCEPTED MANUSCRIPT 6 bone/serum concentration ratios of 0.2-0.5 are found in humans (reviewed in [14]).…”

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confidence: 99%

The use of rifampin in staphylococcal orthopaedic-device-related infections

Sendi

Zimmerli

2017

Clinical Microbiology and Infection

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“…(This work was presented in part at the 32nd Intersciencei1 7 within-subject comparative study. Two 3-day active treatment periods were programmed (fleroxacin alone and fleroxacin plus rifampin) to achieve steady-state conditions.…”

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Influence of rifampin on fleroxacin pharmacokinetics

Schrenzel

Dayer

Leemann

et al. 1993

Antimicrob Agents Chemother

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Staphylococcus aureus infections have been successfully treated in animal models with the combination of fleroxacin and rifampin. We studied the influence of rifampin, a potent cytochrome P-450 inducer, on the pharmacokinetics and biotransformation of fleroxacin in 14 healthy young male volunteers. Subjects were given 400 mg of fleroxacin orally once a day for 3 days to reach steady state. After a wash-out period of 2 days, the same subjects received 600 mg of rifampin orally once daily for 7 days. On days 5 to 7 of rifampin treatment, 400 mg of fleroxacin was again administered once daily. Concentrations of fleroxacin as well as its two major urinary metabolites, N-demethyl-and N-oxide-fleroxacin, in plasma and urine were determined by reverse-phase high-performance liquid chromatography. The extent of hepatic enzyme induction by rifampin was confirmed by a significant increase of 6-13-hydroxycortisol urinary output from 160.8 ± 41.4 to 544.8 ± 120.7 ,ug/4 h. There were no significant changes in the peak fleroxacin concentration in plasma (6.3 ± 1.2 versus 6.2 ± 1.9 mg/liter), time to maximum concentration of fleroxacin in plasma (1.1 ± 0.9 versus 1.3 ± 1.1 h), or renal clearance (58.3 ± 16.4 versus 61.9 ± 19.2 mVmin). The area under the curve AUC (71.4 ± 15.8 versus 62.2 ± 13.7 mg. h/liter) and the terminal half-life of fleroxacin (11.4 ± 2.2 versus 9.2 + 1.1 h) decreased (P < 0.05), while the total plasma clearance increased from 97.7 ± 21.6 to 112.3 ± 25.8 ml/min (P < 0.01).Despite being statistically significant, this 15% increase in total plasma clearance does not appear to be clinically relevant. Metabolic clearance by N demethylation was increased (6.9 ± 2.4 versus 12.5 ± 3.2 ml/min; P < 0.01), whereas clearance by N oxidation did not change (5.8 ± 1.1 versus 5.8 ± 1.5 ml/min). Fleroxacin elimination was slightly increased (about 15%) through induction of metabolic clearance to N-demethylfleroxacin. Since fleroxacin levels remained above the MIC for 90%o of the tested isolates of methicillinsusceptible S. aureus for at least 24 h, dose adjustment does not appear necessary, at least for short-term treatments.Fluoroquinolones, including fleroxacin, have recently emerged as interesting antibacterial agents in the therapy of deep-seated infections. This is in part attributable to their antibacterial spectra, the extent of their oral absorption, and their high rate of penetration into biological fluids and tissues (45).Rifampin has long been used as an adjunctive treatment of staphylococcal infections because of its antibacterial effects on staphylococci and its extensive distribution into tissues. However, rifampin monotherapy almost invariably leads to failure due to development of resistance. The combined use of both families of antibacterial agents, fluoroquinolones and rifampin, has been advocated for the treatment of serious staphylococcal infections to avoid the emergence of resistant bacteria, especially in long-term treatments (3, 14-16, 22, 23, 25, 26, 28, 35, 38, 44, 48).The combination of fleroxa...

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Multiple-dose pharmacokinetics of concurrent oral ciprofloxacin and rifampin therapy in elderly patients

Cited by 35 publications

References 27 publications

Crossover assessment of serum bactericidal activity and pharmacokinetics of ciprofloxacin alone and in combination in healthy elderly volunteers

Crossover assessment of serum bactericidal activity and pharmacokinetics of ciprofloxacin alone and in combination in healthy elderly volunteers

The use of rifampin in staphylococcal orthopaedic-device-related infections

Influence of rifampin on fleroxacin pharmacokinetics

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