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.

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.

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.

scholarly journals Tissue Penetration by Ertapenem, a Parenteral Carbapenem Administered Once Daily, in Suction-Induced Skin Blister Fluid in Healthy Young Volunteers

2003 ◽  
Vol 47 (4) ◽  
pp. 1439-1442 ◽  
Author(s):  
T. Laethem ◽  
I. De Lepeleire ◽  
J. McCrea ◽  
J. Zhang ◽  
A. Majumdar ◽  
...  
Keyword(s):  
Confidence Interval ◽  
Blister Fluid ◽  
Tissue Penetration ◽  
Time Curve ◽  
Once Daily ◽  
Dosing Interval ◽  
Concentration Time ◽  
Skin Blister

ABSTRACT The penetration of 1 g of intravenous ertapenem once daily for 3 days in suction-induced skin blisters was evaluated. Ten forearm blisters were formed (n = 12) 12 h prior to the last dose. Concentrations of ertapenem in blister fluid exceeded 4 μg/ml (the MIC at which 90% of the isolates tested are eliminated) for the entire dosing interval. The area under the concentration-time curve for 0 to 24 h ratio of blister fluid to plasma was 61% (90% confidence interval, 56, 65%) suggesting good blister penetration.

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.

scholarly journals Association between the Pharmacokinetics and In Vivo Therapeutic Efficacy of Sulfadoxine-Pyrimethamine in Malawian Children

2005 ◽  
Vol 49 (9) ◽  
pp. 3601-3606 ◽  
Author(s):  
Fraction K. Dzinjalamala ◽  
Allan Macheso ◽  
James G. Kublin ◽  
Terrie E. Taylor ◽  
Karen I. Barnes ◽  
...  
Keyword(s):  
Terminal Phase ◽  
Time Curve ◽  
Mean Values ◽  
Concentration Time ◽  
Elimination Half ◽  
Resistant Genotypes ◽  
Parasitological Response ◽  
Phase Elimination ◽  
Malaria Risk Factors

ABSTRACT Sulfadoxine-pyrimethamine (SP) has been widely used in recent years to treat acute uncomplicated Plasmodium falciparum malaria. Risk factors for SP therapeutic failure include young age, subtherapeutic SP concentrations, and resistance-conferring genetic mutations in parasite target enzymes. A substantial proportion of patients are able to clear genetically highly resistant P. falciparum genotypes. To determine whether blood SP concentrations independently affect the patient's ability to clear resistant genotypes, we compared SP pharmacokinetics of cases of adequate clinical and parasitological response (ACPR) with cases of treatment failure (TF). When patients with ACPR and TF were compared, mean values were similar for the day 3 blood pyrimethamine (205 ng/ml versus 172 ng/ml; P = 0.25) and estimated maximum sulfadoxine (79 ± 6.52 versus 69 ± 6.27 μg/ml; P = 0.60) concentrations, for sulfadoxine terminal-phase elimination half-lives (7.15 versus 6.41 days; P = 0.42), and for the extents of sulfadoxine absorption (areas under the concentration-time curve of 932 ± 100 versus 888 ± 78.9 μg day ml−1; P = 0.72). Among patients infected with the quintuple resistant parasites, day 3 blood pyrimethamine concentrations were higher in those who cleared the infection than in those who did not (305 ± 35.4 versus 228 ± 21.7 ng/ml; P = 0.037). Within this subgroup, this finding remained significant after adjusting for endogenous folate levels, age, site, and resistance-conferring mutations (odds ratio: 1.011 [1.003 to 1.024]; P = 0.018). However, as a subgroup analysis, our biologically plausible observation that higher blood pyrimethamine concentrations enhance the ability of patients to clear resistant P. falciparum should be interpreted with caution and needs further validation.

scholarly journals PHARMACODYNAMICS EFFECT OF METHYLPREDNISOLONE TABLETS ON THE SERUM CONCENTRATION OF ANNEXIN A1: IN VIVO COMPARATIVE STUDY BETWEEN GENERIC AND INNOVATOR DRUG

2019 ◽  
Vol 12 (1) ◽  
pp. 414
Author(s):  
Hansen Nasif ◽  
Henny Lucida ◽  
Yanwirasti Yanwirasti ◽  
Yufri Aldi ◽  
Yori Yuliandra
Keyword(s):  
Serum Concentration ◽  
Peak Concentration ◽  
Peak Time ◽  
Annexin A1 ◽  
Onset Of Action ◽  
Time Curve ◽  
Concentration Time ◽  
Significant Difference ◽  
Generic Products

Objective: The aims of this study were to investigate the comparative pharmacodynamics effect of methylprednisolone (MP) innovator, MP branded generic, and MP generic products to the serum concentration of annexin A1 (AnxA1).Methods: It was conducted by two-way crossover design in male rabbits. AnxA1 was measured at 0, 0.5, 1, 2, 3, 5, 7, and 9 h after the administration of the drugs. The peak concentration (Cmax), the time at which the peak concentration was achieved (Tmax), and the area under the plasma concentration-time curve (AUC) were also determined.Results: The highest concentration and widest AUC of AnxA1 were obtained in MP innovator drug. MP innovator and branded generic reaches the peak time (Tmax) at the third 3rd h, while the MP generic reaches the peak time at the 5th h. The results showed that there was no significant difference in the serum concentration of AnxA1 between MP tablets after analyzed with a one-way analysis of variance.Conclusion: It could be concluded that the innovator drug of MP tablet gave the same effect on the serum concentration of AnxA1 than its generic counterparts, but an onset of action MP innovator and branded generic is faster than the generic product.

scholarly journals Kill kinetics and regrowth patterns of Pseudomonas aeruginosa exposed to concentration-time profiles of tobramycin simulating in vivo infusion and bolus dosing.

1996 ◽  
Vol 40 (5) ◽  
pp. 1321-1324
Author(s):  
P J Wood ◽  
L L Ioannides-Demos ◽  
E B Bastone ◽  
W J Spicer ◽  
A J McLean
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Peak Concentration ◽  
Bacteriostatic Activity ◽  
Antibiotic Concentration ◽  
Initial Profile ◽  
Time Curve ◽  
Time Profiles ◽  
Concentration Time

Pseudomonas aeruginosa ATCC 27853 was exposed to tobramycin concentration-time profiles modelling in vivo bolus and infusion dosing. Dependence of bactericidal and bacteriostatic activity on the initial profile of peak concentration (bolus effect > infusion) and area under the antibiotic concentration-time curve was observed at peak concentration/MIC ratios of 10 or below.

scholarly journals Preclinical Development of Inhalable D-Cycloserine and Ethionamide To Overcome Pharmacokinetic Interaction and Enhance Efficacy against Mycobacterium tuberculosis

2019 ◽  
Vol 63 (6) ◽  
Author(s):  
Rajeev Ranjan ◽  
Ashish Srivastava ◽  
Reena Bharti ◽  
Trisha Roy ◽  
Sonia Verma ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Bactericidal Activity ◽  
Half Life ◽  
Pharmacokinetic Interaction ◽  
Preclinical Development ◽  
Time Curve ◽  
Content Type ◽  
Concentration Time ◽  
Oral Doses ◽  
Plasma Half Life

ABSTRACT We compared the pharmacokinetics and efficacy of a combination of d-cycloserine (DCS) and ethionamide (ETO) via oral and inhalation routes in mice. The plasma half-life (t1/2) of oral ETO at a human-equivalent dose decreased from 4.63 ± 0.61 h to 1.64 ± 0.40 h when DCS was coadministered. The area under the concentration-time curve from 0 h to time t (AUC0–t) was reduced to one-third. Inhalation overcame the interaction. Inhalation, but not oral doses, reduced the lung CFU/g of Mycobacterium tuberculosis H37Rv from 6 to 3 log10 in 4 weeks, indicating bactericidal activity.

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