The Influence of Protein Binding upon Tissue Fluid Levels of Six  -Lactam Antibiotics

Wise, R.; Gillett, A.P.; Cadge, B.; Durham, S.R.; Baker, Scott

doi:10.1093/infdis/142.1.77

Cited by 146 publications

(83 citation statements)

References 16 publications

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“…Studies showing that sites such as cerebrospinal fluid (34) and abscess cavities (3) had drug concentrations lower than those in blood reinforced the contention of lower antibiotic concentrations at extravascular infection sites. Subsequent studies which demonstrated low concentrations in extravascular fluid models (8,18,64) further emphasized this hypothesis. Furthermore, studies proposed that protein binding inhibited extravascular penetration (2,11,22,39) and implied that antibiotics highly bound to serum proteins had to be used at higher dosages to be as effective as antibiotics exhibiting low serum protein binding (2,11,26).…”

mentioning

confidence: 97%

Antibiotic tissue penetration and its relevance: models of tissue penetration and their meaning

Nix

Goodwin

Peloquin

et al. 1991

Antimicrob Agents Chemother

133

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mentioning

confidence: 97%

Antibiotic tissue penetration and its relevance: models of tissue penetration and their meaning

Nix

Goodwin

Peloquin

et al. 1991

Antimicrob Agents Chemother

133

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“…In this open-label crossover study, the pharmacokinetics and penetration of levofloxacin into an inflammatory exudate that mimics skin and soft tissue infections were examined following administration of 500-mg doses every 12 or 24 h. The penetration of this agent into an artificially induced inflammatory exudate was investigated by employing the cantharidin-impregnated plaster technique (14).…”

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confidence: 99%

Open-label crossover study to determine pharmacokinetics and penetration of two dose regimens of levofloxacin into inflammatory fluid

Child

Mortiboy

Andrews

et al. 1995

Antimicrob Agents Chemother

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Two levofloxacin administration regimens were used for six healthy male volunteers. They received either 500 mg of levofloxacin orally every 12 h for five doses or 500 mg every 24 h for three doses, and then 6 weeks later they received the other course. The concentrations of the drug in plasma, cantharidin-induced inflammatory fluid, and urine were measured with a microbiological assay following administration of the final dose. Mean peak concentrations in plasma of 9.3 and 6.6 g/ml were attained 1.1 and 1.2 h after the 12-and 24-h regimens, respectively. Mean peak concentrations in inflammatory fluid of 6.8 and 4.3 g/ml were attained at 2.3 and 3.7 h, respectively. The average steady-state concentrations were 5.0 and 2.2 g/ml in plasma and 4.7 and 2.3 g/ml in inflammatory fluid, respectively. The mean terminal elimination half-lives for plasma were 7.9 and 8.0 h for the two regimens, respectively, and the same values were noted for inflammatory fluid. The overall penetration into inflammatory fluid ranged from 88 to 101% with the 12-h regimen and 83 to 112% with the 24-h regimen. Mean urinary recoveries were 87 and 86% over the corresponding interval of the 12-and 24-h regimens, respectively. These results suggest that administration of levofloxacin once and twice daily should be efficacious for infections caused by the majority of pathogens.

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“…The purpose of this study was to investigate the pharmacokinetics of grepafloxacin in healthy volunteers following a single 400-mg dose and to investigate the penetration into inflammatory fluid with a chemically induced blister as a model (13).…”

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Pharmacokinetics and tissue penetration of the new fluoroquinolone grepafloxacin

Child

Andrews

Wise

1995

Antimicrob Agents Chemother

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A single 400-mg oral dose of grepafloxacin (OPC-17116) was given to each of six healthy male volunteers, and the concentrations of the drug in plasma, cantharides-induced inflammatory fluid, and urine were measured over the subsequent 12 h. The mean peak concentration in plasma of 1.5 g/ml was attained at a mean time of 2.0 h postdose. The mean peak concentration in inflammatory fluid of 1.1 g/ml was attained at a mean time of 4.8 h postdose. The mean elimination half-life in plasma was 5.2 h, and that in inflammatory fluid was 12.7 h. The overall penetration into inflammatory fluid was 180.6% (or 133% if one aberrant result from one volunteer is excluded). Recovery of the drug in urine during the first 24 h postdose was 8.3% of the administered dose. Our results indicate that a once-or twice-daily dosage of grepafloxacin should be adequate to treat systemic infections caused by most bacterial pathogens.Grepafloxacin (OPC-17116) is a new, oral fluoroquinolone which is characterized as having an N-1 cyclopropyl group, a C-5 methyl group, and a C-7 piperazinyl moiety to which a 3-methyl group is attached. In vitro studies suggest that in comparison with the earlier quinolones, grepafloxacin has enhanced activity against gram-positive cocci, including Streptococcus pneumoniae, Enterococcus species, and methicillin-susceptible Staphylococcus aureus (5,8,9,12). It also appears to be more active against anaerobes, particularly Bacteroides species. One study demonstrated activity against chlamydial species, including Chlamydia pneumoniae, that was greater than that of ciprofloxacin or tetracycline (12).The purpose of this study was to investigate the pharmacokinetics of grepafloxacin in healthy volunteers following a single 400-mg dose and to investigate the penetration into inflammatory fluid with a chemically induced blister as a model (13). MATERIALS AND METHODSApproval for this study was obtained from the Hospital Ethical Committee. Six healthy, Caucasian male volunteers with a mean age of 28 years (range, 22 to 37 years), a mean weight of 73.08 kg (range, 60 to 89.4 kg), and a mean height of 1.77 m (range, 1.69 to 1.85 m) were selected. None had a history of atopy or of allergy to antibiotics or had taken any prescribed or over-the-counter medication in the 4 and 2 weeks, respectively, prior to the study. Results of physical examinations, biochemical and hematological profiles, and urinalyses were within normal limits in the 9 days prior to the study. Vital signs, including sitting blood pressure, pulse, respiratory rate, and oral temperature, were checked immediately prior to dosing and after the study. Two 1.5-cm 2 plasters impregnated with 0.2% cantharides were taped to the forearm of each volunteer approximately 12 to 16 h prior to dosing. After an overnight fast, the volunteers were given 400 mg of grepafloxacin (provided by Otsuka Pharmaceutical Company, London, United Kingdom) to be taken orally with 200 ml of water. They fasted for a further 2 h after the dose, at which time they were permitted to have a l...

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The Influence of Protein Binding upon Tissue Fluid Levels of Six -Lactam Antibiotics

Cited by 146 publications

References 16 publications

Antibiotic tissue penetration and its relevance: models of tissue penetration and their meaning

Antibiotic tissue penetration and its relevance: models of tissue penetration and their meaning

Open-label crossover study to determine pharmacokinetics and penetration of two dose regimens of levofloxacin into inflammatory fluid

Pharmacokinetics and tissue penetration of the new fluoroquinolone grepafloxacin

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