Ciprofloxacin pharmacokinetics in patients with cystic fibrosis

Sw, Bender; Dalhoff, A.; Pm, Shah; Strehl, Raimund; Hg, Posselt

doi:10.1007/bf01644804

Cited by 34 publications

(17 citation statements)

References 34 publications

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“…Other investigators have reported mean bioavailabilities of 56 to 77% in normal volunteers (13,30,32), values which are not altered by administering ciprofloxacin with meals (17). (11,30) or those determined by a microbiological assay (3,4,6,12,22,32). This last finding is surprising in view of the fact that ciprofloxacin is metabolized to microbiologically active compounds that are eliminated in the urine (14 70-kg adult) (7) and is in good agreement with results obtained by other investigators (6,12).…”

Section: Discussionmentioning

confidence: 99%

Pharmacokinetics of ciprofloxacin in cystic fibrosis

Davis¹,

Koup²,

Williams‐Warren³

et al. 1987

Antimicrob Agents Chemother

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We studied the pharmacokinetics of ciprofloxacin in 12 adult males with and 12 adult males without cystic fibrosis (CF). In a randonized crossover sequence, the subjects received 200 mg intravenously or 750 mg orally. With intravenous dosing, subjects also received 651 mg of iothalamate, a marker of glomerular ifitration, and 700 mg of antipyrine, an indicator of hepatic oxidative drug metabolism. Pharmacokinetic parameters were determined by model independent methods. In the CF subjects, the ciprofloxacin concentration in serum during the first hour after intravenous administration was higher, and the oral absorption rate was slower. Other parameters did not differ between the groups. Mean concentrations in serum 5 min postinfusion were 3.08 and 2.14 ,Ig/mn, and mean peak concentrations after oral dosing were 3.24 and 3.34 ,ug/ml in subjects with and without CF, respectively, Mean values for elimination half-life in all subjects were 4.8 and 5.0 h after intravenous and oral administration, respectively. The mean renal clearances in all subjects after intravenous and oral administration were 19.4 and 14.5 liters/h and accounted for 64 and 47% of the total clearance, respectively. These values were significantly greater than renal iothalamate clearance, indicating that tubular secretion contributed to the renal clearance of ciprofloxacin. A total of 69 and 35.4% of the administered ciprofloxacin was recovered from the urine within 48 h after intravenous and oral administration, respectively. The mean bioavailability was 71.2% and did not differ between the groups. We conclude that similar dosing regimens can be used to treat patients with CF and their normal counterparts.Respiratory infections caused by Pseudomonas aeruginosa, Haemophilus influenzae, and Staphylococcus aureus are responsible for much of the morbidity and mortality in patients with cystic fibrosis (CF) (15). Ciprofloxacin is a quinoline antibiotic which posesses activity against these and other organisms (2,9,19, 31).Patients with CF have altered pharmacokinetics of some drugs as compared with their normal counterparts (15). The purpose of this study was to compare the pharmacokinetics of ciprofloxacin after intravenous and oral administration in subjects with CF to that in subjects without any known disease states. MATERIALS AND METHODSSubjects. A total of 12 male subjects with CF (ages 18 to 34) and 12 male volunteers without CF (ages 23 to 32) were enrolled in the study after informed consent was obtained. The study was approved by the Human Subjects Review Board at our university. All subjects abstained from alcohol-containing beverages for 72 h before and 48 h after administration of the study drugs. Subjects with CF abstained from alcohol but took their usual medications (multivitamins, pancreatic enzymes, and bronchodilators). All subjects were reexamined and laboratory tests were repeated within 72 h after the final dose of ciprofloxacin.Drug administration. In a randomized, crossover sequence, volunteers received 200 mg of ciprofloxacin...

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Section: Discussionmentioning

confidence: 99%

Pharmacokinetics of ciprofloxacin in cystic fibrosis

Davis¹,

Koup²,

Williams‐Warren³

et al. 1987

Antimicrob Agents Chemother

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“…Concentrations of ciprofloxacin in lung tissue homogenates or ELF are as high as 15 to 29 mg/liter (Table 2) (144)(145)(146)(147)(148).…”

Section: Serum and Sputum Pharmacokineticsmentioning

confidence: 99%

“…In vitro exposure of P. aeruginosa to fluctuating enoxacin serum concentrations following oral doses of 500 mg/day administered either once or twice daily for 2 days resulted in rapid emergence of resistance due to the selection of moderately resistant subpopulations (243). A population analysis of four P. aeruginosa strains isolated from adult CF patients who were treated in 1983 for the first time in their lives with 500 mg ciprofloxacin orally twice daily (145) revealed that the preexposure isolates were heterogeneously susceptible to ciprofloxacin, with MICs for the subpopulations ranging from Յ1-to up to 16-fold the MIC of ciprofloxacin, as determined for the entire population by the CLSI method (97). These strains were exposed in vitro for 5 days to fluctuating ciprofloxacin concentrations simulating an oral 500-mg b.i.d.…”

Section: Emergence Of Resistance In Pk/pd Studies and In Cf Patientsmentioning

confidence: 99%

“…A genomic analysis of one P. aeruginosa strain revealed that 35 different genes were involved in ciprofloxacin resistance; 10 of these were regulated by ciprofloxacin (235). Three studies (145,243,244) demonstrated that heterogeneous bacterial populations provide a reservoir for resis- a These isolates were exposed in vitro to fluctuating ciprofloxacin concentrations simulating an oral twice-daily dose of 500 mg. The CLSI MIC was generated by selecting at least three to five well-isolated colonies of the same morphological type for preparation of the inoculum.…”

Section: Emergence Of Resistance In Pk/pd Studies and In Cf Patientsmentioning

confidence: 99%

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Pharmacokinetics and Pharmacodynamics of Aerosolized Antibacterial Agents in Chronically Infected Cystic Fibrosis Patients

Dalhoff¹

2014

Clin Microbiol Rev

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SUMMARY Bacteria adapt to growth in lungs of patients with cystic fibrosis (CF) by selection of heterogeneously resistant variants that are not detected by conventional susceptibility testing but are selected for rapidly during antibacterial treatment. Therefore, total bacterial counts and antibiotic susceptibilities are misleading indicators of infection and are not helpful as guides for therapy decisions or efficacy endpoints. High drug concentrations delivered by aerosol may maximize efficacy, as decreased drug susceptibilities of the pathogens are compensated for by high target site concentrations. However, reductions of the bacterial load in sputum and improvements in lung function were within the same ranges following aerosolized and conventional therapies. Furthermore, the use of conventional pharmacokinetic/pharmacodynamic (PK/PD) surrogates correlating pharmacokinetics in serum with clinical cure and presumed or proven eradication of the pathogen as a basis for PK/PD investigations in CF patients is irrelevant, as minimization of systemic exposure is one of the main objectives of aerosolized therapy; in addition, bacterial pathogens cannot be eradicated, and chronic infection cannot be cured. Consequently, conventional PK/PD surrogates are not applicable to CF patients. It is nonetheless obvious that systemic exposure of patients, with all its sequelae, is minimized and that the burden of oral treatment for CF patients suffering from chronic infections is reduced.

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“…It is a p-glycoprotein and active transport substrate in various drug disposition pathways (173,175,178,282). After an administration of a single oral dose (500mg), the AUC 0-∞ observed in Brazilian subjects was 1.5 to 4-fold smaller than that observed in German, Caucasian, US American, Indonesian and Chinese subjects (135)(136)(137)(138)(139)(140). A significantly higher ciprofloxacin AUC 0-∞ has been observed in Nigerian and Chinese compared with German subjects as well when administered intravenously (139,141,142).…”

Section: Fluoroquinolones -Ciprofloxacin Is Moderately Lipophilic Andmentioning

confidence: 99%

Improving antibiotic dosing in critically ill Australian Indigenous patients with severe sepsis

Tsai¹

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Sepsis is a major health issue in the Australian Indigenous population. Unfortunately, the high rates of mortality and morbidity caused by sepsis or severe sepsis in this population have not significantly reduced over recent decades. Research into the role of optimisation of antibiotic therapy for improving patient outcomes is certainly an important area of need. In other patient populations, there is increasing evidence of an improvement of clinical cure rates and survival in patients with severe sepsis when antibiotic dosing results in therapeutic concentrations, that is, achieves pharmacokinetic/pharmacodynamic (PK/PD) targets. However, numerous PK changes caused by the altered physiology associated with critical illness may reduce the likelihood of such effective dosing.Previous studies have identified a number of physiological characteristics in the Australian Indigenous population which suggest that interethnic PK differences are likely in comparison with the non-Indigenous. As most PK data of antibiotics were obtained from healthy Caucasian volunteers, whether these data can be extrapolated to the critically ill Indigenous patients requires investigation.The aims of this thesis are to describe the PK of meropenem, ceftriaxone, vancomycin and piperacillin in severely septic Indigenous patients; compare the PK with existing data from nonIndigenous patients; design optimised dosing regimens for each of the study antibiotics; and quantify the variation in renal function of critically ill Indigenous patients. This thesis consists of nine Chapters:Chapter one provides an overview of the current clinical challenges encountered in antibiotic dosing in critically ill patients. It also discusses specific physiological characteristics of Australian Indigenous patients which may lead to different PK compared with non-Indigenous comparators.Chapter two comprises of a narrative review which discusses the PK/PD factors that should be considered when prescribing antibiotics to critically ill patients. This Chapter summarises data which describe an improvement in clinical outcome when antibiotics achieve PK/PD targets. ThisChapter concludes to support an individualised approach to dosing antibiotics as opposed to the 'one dose fits all' approach that is common to clinical practice.ii Chapter three incorporates a systematic review which investigates the published data describing differences in antibiotic PK between different ethnic groups. No reports on PK in Indigenous Australians were found. The predominant data described differences in PK between the Asian and Caucasian ethnicities. Typically, Asian subjects manifested higher antibiotic concentrations for antibiotics that have significant hepatic metabolism, are substrates to p-glycoprotein or other forms of active transport and/or have high alpha-1-acid glycoprotein binding.Chapter four incorporates a study which described the renal function of critically ill Australian Indigenous patients. This study found a numerically higher incidence of augmented renal clea...

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Ciprofloxacin pharmacokinetics in patients with cystic fibrosis

Cited by 34 publications

References 34 publications

Pharmacokinetics of ciprofloxacin in cystic fibrosis

Pharmacokinetics of ciprofloxacin in cystic fibrosis

Pharmacokinetics and Pharmacodynamics of Aerosolized Antibacterial Agents in Chronically Infected Cystic Fibrosis Patients

Improving antibiotic dosing in critically ill Australian Indigenous patients with severe sepsis

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