scholarly journals Single-Dose Pharmacokinetics and Penetration of BMS 284756 into an Inflammatory Exudate

2002 ◽  
Vol 46 (1) ◽  
pp. 242-244 ◽  
Author(s):  
R. Wise ◽  
T. Gee ◽  
G. Marshall ◽  
J. M. Andrews
Keyword(s):  
Single Dose ◽  
Standard Deviation ◽  
Oral Administration ◽  
Peak Concentration ◽  
Healthy Male ◽  
Inflammatory Exudate ◽  
Concentration Time ◽  
Elimination Half ◽  
The Mean ◽  
Mean Time

ABSTRACT The pharmacokinetics of a single dose of BMS 284756 were determined following oral administration of a 600-mg dose to eight healthy male volunteers. Concentrations of the drug were measured in plasma and a cantharidine-induced inflammatory exudate by a microbiological assay. The mean peak concentration in plasma of 10.4 μg/ml (standard deviation [SD], 1.3 μg/ml) was attained at a mean time of 1.2 h (SD, 0.5 h) after the dose. The penetration into the inflammatory exudate was 82% (SD, 15.7%). A mean peak concentration of 7.2 μg/ml (SD, 2.4 μg/ml) was attained in the inflammatory exudate at 5.3 h (SD, 1.5 h). The elimination half-lives from plasma and inflammatory fluid were 9.8 h (SD, 1.1 h) and 8.5 h (SD, 1.9 h), respectively. The areas under the concentration-time curves for plasma and inflammatory fluid were 96.7 μg · h/ml (SD, 10.3 μg · h/ml) and 77.9 μg · h/ml (SD, 19.2 μg · h/ml), respectively.

scholarly journals Pharmacokinetics and Tissue Penetration of Linezolid following Multiple Oral Doses

2001 ◽  
Vol 45 (6) ◽  
pp. 1843-1846 ◽  
Author(s):  
Thekli Gee ◽  
Richard Ellis ◽  
Gillian Marshall ◽  
Jenny Andrews ◽  
Janet Ashby ◽  
...  
Keyword(s):  
Peak Concentration ◽  
Blister Fluid ◽  
Healthy Male ◽  
Tissue Penetration ◽  
Final Dose ◽  
Time Curve ◽  
Concentration Time ◽  
Elimination Half ◽  
Oral Doses ◽  
Mean Time

ABSTRACT The pharmacokinetics of multiple-dose linezolid were determined following administration of five 600-mg oral doses given every 12 h to each of six healthy male volunteers. Concentrations of the drug were determined in plasma and inflammatory blister fluid using high-pressure liquid chromatography. A mean peak concentration in plasma of 18.3 μg/ml (standard deviation [SD], 6.0) was attained at a mean time of 0.7 h (SD, 0.3) after the final dose. The penetration into the inflammatory fluid was 104% (SD, 20.7). A mean peak concentration of 16.4 μg/ml (SD, 10.6) was attained in the inflammatory fluid at 3 h (SD, 0.6) after the final dose. The elimination half-life from serum and inflammatory fluid was 4.9 (SD, 1.8) and 5.7 (SD, 1.7) h, respectively. The area under the concentration-time curve in plasma and blister fluid was 140.3 (SD, 73.1) and 155.3 (SD, 80.1) μg · h/ml, respectively. These data suggest that linezolid has good tissue penetration, and we can predict that it will be successful in the treatment of a variety of gram-positive infections.

Pharmacokinetics and Inflammatory Fluid Penetration of Clinafloxacin

1998 ◽  
Vol 42 (2) ◽  
pp. 428-430 ◽  
Author(s):  
R. Wise ◽  
S. Jones ◽  
I. Das ◽  
J. M. Andrews
Keyword(s):  
Half Life ◽  
Maximum Concentration ◽  
Healthy Male ◽  
Elimination Half Life ◽  
Concentration Time ◽  
Healthy Male Volunteers ◽  
Elimination Half ◽  
The Mean ◽  
Fluid Penetration ◽  
Mean Time

ABSTRACT A single 200-mg dose of clinafloxacin was given orally to each of nine healthy male volunteers, and the concentrations of the drug were measured in plasma, cantharidin-induced inflammatory fluid, and urine over the following 24 h (48 h in the case of urine). The mean maximum concentration in plasma was 1.34 μg/ml at a mean time of 1.8 h postdose. The mean maximum concentration in the inflammatory fluid was 1.3 μg/ml at 3.8 h postdose. The mean elimination half-life of clinafloxacin in plasma was 5.65 h. The overall penetration into the inflammatory fluid was 93.1%, as assessed by determining the ratio of area under the concentration-time curves. Recovery of clinafloxacin in urine was 58.8% by 24 h and 71.8% by 48 h postdose.

scholarly journals Pharmacokinetics and Inflammatory Fluid Penetration of Intravenous Daptomycin in Volunteers

2002 ◽  
Vol 46 (1) ◽  
pp. 31-33 ◽  
Author(s):  
R. Wise ◽  
T. Gee ◽  
J. M. Andrews ◽  
B. Dvorchik ◽  
G. Marshall
Keyword(s):  
Body Weight ◽  
Standard Deviation ◽  
Total Drug ◽  
Healthy Male ◽  
Urinary Recovery ◽  
Time Curve ◽  
Concentration Time ◽  
Elimination Half ◽  
The Mean ◽  
Fluid Penetration

ABSTRACT The lipopeptide antimicrobial daptomycin was administered intravenously at a dose of 4 mg/kg of body weight to seven healthy male volunteers. The concentrations of daptomycin in plasma, cantharidin-induced inflammatory fluid, and urine were measured by a microbiological assay. The mean ± standard deviation peak concentrations in plasma and inflammatory fluid were 77.5 ± 8.3 and 27.6 ± 9.5 μg/ml, respectively; the mean terminal elimination half-lives were 7.74 and 13.2 h, respectively. The overall penetration of total drug into the inflammatory fluid (measured by ratio of the area under the concentration-time curve from 0 to 24 h for inflammatory fluid compared with that for plasma) was 68.4%. The mean urinary recovery over 24 h was 59.7%.

Pharmacokinetics and penetration into inflammatory fluid of trovafloxacin (CP-99,219).

1996 ◽  
Vol 40 (1) ◽  
pp. 47-49 ◽  
Author(s):  
R Wise ◽  
D Mortiboy ◽  
J Child ◽  
J M Andrews
Keyword(s):  
Oral Dose ◽  
Half Life ◽  
Maximum Concentration ◽  
Healthy Male ◽  
Elimination Half Life ◽  
Concentration Time ◽  
Elimination Half ◽  
The Mean ◽  
Systemic Infections ◽  
Mean Time

A single 200-mg oral dose of trovafloxacin (CP-99,219) was given to each of eight healthy male volunteers, and the concentrations of the drug were measured in plasma, cantharides-induced inflammatory fluid, and urine over the subsequent 36 h. The mean maximum concentration observed in plasma was 2.9 micrograms/ml at a mean time of 0.75 h postdose. The mean maximum concentration observed in inflammatory fluid was 1.2 micrograms/ml at 4.0 h postdose. The mean elimination half-life in plasma was 7.8 h. The overall penetration into inflammatory fluid was 64%, as assessed by determining the ratio of the area under the concentration-time curves. Recovery of the dose in urine within the first 36 h postdose was 5.0% of the administered dose. Our results indicate that trovafloxacin, at a dosage of 200 mg once or twice daily, should be adequate for the treatment of systemic infections caused by most common bacterial pathogens.

A study to determine the pharmacokinetics and inflammatory fluid penetration of two doses of a solid formulation of the hexetil prodrug of a trinem, sanfetrinem (GV 104326).

1997 ◽  
Vol 41 (8) ◽  
pp. 1761-1764 ◽  
Author(s):  
R Wise ◽  
J M Andrews ◽  
L Da Ros ◽  
J Child ◽  
D Mortiboy
Keyword(s):  
Single Dose ◽  
Dose Equivalent ◽  
Inflammatory Exudate ◽  
The Poor ◽  
Elimination Half ◽  
The Mean ◽  
The Stability ◽  
Fluid Penetration ◽  
Dose Levels

The trinem sanfetrinem (GV 104326) was administered as the oral hexetil prodrug GV 118819X in two dose levels to six healthy volunteers. A single dose equivalent to 125 mg of sanfetrinem was administered, followed 6 weeks later by a single dose equivalent to 500 mg of sanfetrinem. The concentrations of the drug in plasma, cantharidin-induced inflammatory fluid, and urine were measured with a microbiological assay. The stability of sanfetrinem was studied in serum and inflammatory fluid. The mean peak concentrations in plasma of 0.77 and 2.47 microg/ml were attained at 1.1 and 2.0 h after the 125- and 500-mg doses, respectively. Mean peak concentrations in inflammatory exudate of 0.26 and 0.86 microg/ml were attained at 2.80 and 2.67 h after the 125- and 500-mg doses, respectively. The mean terminal elimination half-lives in plasma were 1.33 and 1.97 h for the 125- and 500-mg doses, respectively. The half-lives in the inflammatory fluid were 1.66 and 1.74 h for the 125- and 500-mg doses, respectively. The overall penetration of the drug into the inflammatory fluid was 51.4 and 47.0% for the 125- and 500-mg doses, respectively. Mean urine recovery was greater following 500 mg (24.15%) than after 125 mg (18.4%) of sanfetrinem. Sanfetrinem was relatively unstable in the inflammatory exudate in vitro (half-life, 5.5 h), and this could explain the poor penetration of the drug in the inflammatory exudate observed in this study.

Do methods of hospital pre-alerts influence the on-scene times for acute pre-hospital stroke patients? A retrospective observational study

2021 ◽  
Vol 6 (2) ◽  
pp. 19-25
Author(s):  
Jacob Gunn
Keyword(s):  
Standard Deviation ◽  
Observational Study ◽  
Acute Stroke ◽  
Ambulance Service ◽  
Time Saving ◽  
North East ◽  
Admission Policies ◽  
The Mean ◽  
Time Critical ◽  
Mean Time

Introduction: Stroke is one of the leading causes of death and disability worldwide. The ambulance service is often the first medical service to reach an acute stroke patient, and due to the time-critical nature of stroke, a time-critical assessment and rapid transport to a hyper acute stroke unit are essential. As stroke services have been centralised, different hospitals have implemented different pre-alert admission policies that may affect the on-scene time of the attending ambulance crew. The aim of this study is to investigate if the different pre-alert admission policies affect time on scene.Method: The current study is a retrospective quantitative observational study using data routinely collected by North East Ambulance Service NHS Foundation Trust. The time on scene was divided into two variables; group one was a telephone pre-alert in which a telephone discussion with the receiving hospital is required before they accept admission of the patient. Group two was a radio-style pre-alert in which the attending clinician makes an autonomous decision on the receiving hospital and alerts them via a short radio message of the incoming patient. These times were then compared to identify if there was any difference between them.Results: Data on 927 patients over a three-month period, from October to December 2019, who had received the full stroke bundle of care, were within the thrombolysis window and recorded as a stroke by the attending clinician, were split into the variable groups and reported on. The mean time on scene for a telephone call pre-alert was 33 minutes and 19 seconds, with a standard deviation of 13 minutes and 8 seconds. The mean on-scene time for a radio pre-alert was 28 minutes and 24 seconds, with a standard deviation of 11 minutes and 51 seconds.Conclusion: A pre-alert given via radio instead of via telephone is shown to have a mean time saving of 4 minutes and 55 seconds, representing an important decrease in time which could be beneficial to patients.

scholarly journals Pharmacokinetics of Intravenous Piperacillin Administration in Patients Undergoing On-Line Hemodiafiltration

2009 ◽  
Vol 53 (8) ◽  
pp. 3266-3268 ◽  
Author(s):  
Kook-Hwan Oh ◽  
Chiweon Kim ◽  
Hankyu Lee ◽  
Hajeong Lee ◽  
Ji Yong Jung ◽  
...  
Keyword(s):  
Standard Deviation ◽  
Total Body Clearance ◽  
Volume Of Distribution ◽  
Pharmacokinetic Parameters ◽  
Recovery Method ◽  
Elimination Half ◽  
On Line ◽  
The Mean ◽  
Total Body ◽  
Body Clearance

ABSTRACT The pharmacokinetic characteristics of piperacillin sodium were studied in five volunteers undergoing on-line hemodiafiltration (HDF). The subjects were given 2 g of piperacillin sodium intravenously over 1 min and placed on on-line HDF for 4 h starting at 60 min after the piperacillin infusion. Noncompartmental models were employed for estimation of the pharmacokinetic parameters, and intradialytic piperacillin clearance was calculated by the recovery method. The mean volume of distribution and the elimination half-life were 0.27 ± 0.13 liter/kg (mean ± standard deviation) and 1.1 ± 0.6 h, respectively. The total body clearance of piperacillin was 0.19 ± 0.08 liter/h/kg. Piperacillin clearance through on-line HDF was 0.11 ± 0.06 liter/h/kg. The mean serum piperacillin concentration was 4.0 ± 1.9 μg/ml at the end of the 4-h on-line HDF session. The concentration of infused piperacillin recovered in the dialysate was 527 ± 236 mg (26.3% ± 11.8%). We suggest the replacement of 500 mg of piperacillin after each on-line HDF session.

scholarly journals CORRELATIONS OF THE MEAN TIME AND MEAN MAGNITUDE OF ACCELERATING PRESHOCKS WITH THE ORIGIN TIME AND MAGNITUDE OF MAINSHOCK

2017 ◽  
Vol 43 (4) ◽  
pp. 2154
Author(s):  
E. M. Scordilis
Keyword(s):  
Standard Deviation ◽  
South America ◽  
Strain Rate ◽  
Central Asia ◽  
Earthquake Prediction ◽  
Critical Region ◽  
Origin Time ◽  
The Mean ◽  
Benioff Strain ◽  
Mean Time

Forty-five preshock sequences preceding corresponding strong (M≥6.4) mainshocks which occurred recently (since 1980) in a variety of seismotectonic regimes (W. Mediterranean, Aegean, Anatolia, California, Japan, Central Asia, South America) have been examined to identify new predictive properties. It has been observed that the mean origin time, , and the mean magnitude, of the accelerating preshocks of each sequence are correlated with the origin time, tc, and the magnitude, M, of the mainshock, respectively. The following relations have been derived: where sa (in Joule ½ /yr.104 Km2 ) is the Benioff strain rate in each preshock (critical) region and σ is the corresponding standard deviation. The possibility for using these relations as constraints in attempts for intermediate term earthquake prediction is discussed.

scholarly journals BMS-284756 in Experimental Cephalosporin-Resistant Pneumococcal Meningitis

2001 ◽  
Vol 45 (11) ◽  
pp. 3098-3103 ◽  
Author(s):  
Violeta Rodriguez-Cerrato ◽  
Faryal Ghaffar ◽  
Jesus Saavedra ◽  
Ian C. Michelow ◽  
Robert D. Hardy ◽  
...  
Keyword(s):  
Antimicrobial Activity ◽  
Cerebrospinal Fluid ◽  
Single Dose ◽  
Standard Deviation ◽  
Pneumococcal Meningitis ◽  
Combined Therapy ◽  
Bactericidal Effect ◽  
Bacterial Killing ◽  
Elimination Half ◽  
Pharmacodynamic Profile

ABSTRACT BMS-284756 is a novel des-fluoro(6) quinolone with a broad antimicrobial activity, including Streptococcus pneumoniae. The purpose of this study was to evaluate the pharmacodynamic profile and effectiveness of BMS-284756 for therapy of experimental meningitis caused by penicillin- and cephalosporin-resistant S. pneumoniae (CRSP). Meningitis was induced in rabbits by intracisternal inoculation of CRSP. BMS-284756 was given intravenously 16 h after intracisternal inoculation in single doses of 2.5 (n = 5 animals), 5 (n = 6), 10 (n = 6), 20 (n = 8), and 30 mg/kg (n = 6), in two doses of 10 mg/kg each separated by 5 h (n = 4), and as a 20-mg/kg dose followed 5 h later by 10 mg/kg (n = 5). The MICs and MBCs of BMS-284756, ceftriaxone, and vancomycin were 0.06 and 0.06, 4 and 4, and 0.25 and 0.25 μg/ml, respectively. After single doses of 10, 20, and 30 mg/kg, the maximum concentrations in cerebrospinal fluid (CSF) (mean ± standard deviation) were 0.32 ± 0.12, 0.81 ± 0.38, and 1.08 ± 0.43 μg/ml, respectively; the elimination half-life in CSF was 4.5 to 6.3 h. The CSF bacterial killing rates (BKR) at 5 h of the single-dose regimens of 10, 20 and 30 mg/kg were −0.84 ± 0.48, −1.09 ± 0.32, and −1.35 ± 0.05 Δlog10 CFU/ml/h. The BKR0–5 of the divided regimens (10 mg/kg twice and 20 mg/kg followed by 10 mg/kg) was −0.82 ± 0.52 and −1.24 ± 0.34 Δlog10CFU/ml/h, respectively. The BKR0–5 of the combined therapy with vancomycin and ceftriaxone was −1.09 ± 0.39 Δlog10 CFU/ml/h. The penetration of BMS-284756 into purulent CSF relative to plasma was 14 to 25%. The bactericidal effect of BMS-284756 in CSF was concentration dependent. BMS-284756 at 30 mg/kg as a single or divided dose was as effective as standard therapy with vancomycin and ceftriaxone.

scholarly journals Safety, toleration, and pharmacokinetics of intravenous azithromycin.

1996 ◽  
Vol 40 (11) ◽  
pp. 2577-2581 ◽  
Author(s):  
D R Luke ◽  
G Foulds ◽  
S F Cohen ◽  
B Levy
Keyword(s):  
Half Life ◽  
Active Drug ◽  
Slow Release ◽  
Volume Of Distribution ◽  
Pharmacokinetic Parameters ◽  
Time Curve ◽  
Concentration Time ◽  
Elimination Half ◽  
The Mean ◽  
Male Subjects

To date, the clinical pharmacology of large intravenous doses of azithromycin has not been described. In the present study, single 2-h intravenous infusions of 1, 2, and 4 g of azithromycin were administered to three parallel groups (in each group, six received active drug and two received placebo) of healthy male subjects. Toleration (assessed by scores of subject-administered visual analog scale tests spanning 0 [good] to 10 [poor]), safety, pharmacokinetics, and serum motilin levels were monitored for up to 240 h after the start of each intravenous infusion. Mean nausea scores of 0.0, 0.0, 1.0, and 0.5 and abdominal cramping scores of 0.0, 0.0, 0.4, and 0.4 for 12-h periods after doses of 0, 1, 2, and 4 g of azithromycin, respectively, suggested that azithromycin was well tolerated. Because of the standardized 1-mg/ml infusates, all subjects in the 4-g dosing group complained of an urgent need to urinate. There were no consistent trends in endogenous motilin levels throughout the study. The maximum concentration of azithromycin in serum (10 micrograms/ml after a 4-g dose) and the area under the concentration-time curve (82 micrograms.h/ml after a 4-g dose) were dose related. The mean pharmacokinetic parameters were an elimination half-life of 69 h, total systemic clearance of 10 ml/min/kg, and a volume of distribution at steady state of 33.3 liters/kg. The pharmacokinetic results suggest that the long half-life of azithromycin is due to extensive uptake and slow release of the drug from tissues rather than an inability to clear the drug. Single intravenous doses of up to 4 g of azithromycin in healthy subjects are generally well tolerated, and quantifiable concentrations may persist in serum for 10 days or more.

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