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 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 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 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 Induction of theophylline clearance by rifampin and rifabutin in healthy male volunteers.

1996 ◽  
Vol 40 (8) ◽  
pp. 1866-1869 ◽  
Author(s):  
J G Gillum ◽  
J M Sesler ◽  
V L Bruzzese ◽  
D S Israel ◽  
R E Polk
Keyword(s):  
Treatment Phase ◽  
Pharmacokinetic Parameters ◽  
Theophylline Clearance ◽  
Healthy Male ◽  
Time Curve ◽  
Concentration Time ◽  
Male Volunteers ◽  
Hepatic Microsomal Enzyme ◽  
The Mean ◽  
To Receive

Rifampin and rifabutin induce the metabolism of many drugs, which may result in subtherapeutic concentrations and failure of therapy. However, differences between rifabutin and rifampin in potency of induction, and the specific enzymes which are altered, are not clear. This study, involving 12 adult male volunteers, compared the effects of 14-day courses of rifampin and rifabutin on clearance of theophylline, a substrate for the hepatic microsomal enzyme CYP1A2. Subjects were given oral theophylline solution (5 mg/kg of body weight) on day 1 and then randomized to receive daily rifampin (300 mg) or rifabutin (300 mg) on days 3 to 16. Theophylline was readministered as described above on day 15. The first treatment sequence was followed by a 2-week washout period; subjects then received the alternative treatment. Theophylline concentrations were determined for 46 h after each dose, and pharmacokinetic parameters were determined. One subject developed flu-like symptoms while taking rifabutin and withdrew voluntarily. Results from the remaining 11 subjects are reported. Compared with the baseline, the mean area under the concentration-time curve (AUC) (+/- standard deviation) for theophylline declined significantly following rifampin treatment (from 140 +/- 37 to 100 +/- 24 micrograms . h/ml, P <0.001); there was no significant change following rifabutin treatment (136 +/- 48 to 128 +/- 45 micrograms.h/ml). Baseline theophylline AUCs before each treatment phase were not different. A comparison of equal doses of rifampin and rifabutin administered to healthy volunteers for 2 weeks indicates that induction of CYP1A2, as measured by theophylline clearance, is significantly less following rifabutin treatment than it is following rifampin treatment. However, the relative induction potency for other metabolic enzymes remains to be investigated.

Efficacy of pharmacokinetic interactions between piperonyl butoxide and albendazole against gastrointestinal nematodiasis in goats

2015 ◽  
Vol 90 (5) ◽  
pp. 624-629 ◽  
Author(s):  
N.K. Kumbhakar ◽  
P.K. Sanyal ◽  
D. Rawte ◽  
D. Kumar ◽  
A.E. Kerketta ◽  
...  
Keyword(s):  
Body Weight ◽  
Half Life ◽  
Maximum Concentration ◽  
Piperonyl Butoxide ◽  
Time Curve ◽  
Concentration Time ◽  
Elimination Half ◽  
Concentration Maximum ◽  
Faecal Egg Count ◽  
Minimum Residence Time

AbstractTo test the hypothesis that modulation of hepatic microsomal sulphoxidation and sulphonation by the cytochrome P450 inhibitor piperonyl butoxide could increase bioavailability of albendazole, the present study was undertaken to understand the pharmacokinetics of albendazole in goats at a dose of 7.5 mg kg− 1 body weight with and without co-administration with piperonyl butoxide at 63.0 mg kg− 1 body weight. Plasma albendazole sulphoxide metabolite, the anthelmintically active moiety, reached its maximum concentration of 0.322 ± 0.045 μg ml− 1 and 0.384 ± 0.013 μg ml− 1 at 18 h and 24 h after administration of albendazole alone and co-administration of albendazole with piperonyl butoxide, respectively. Analysis of the data revealed statistically increased albendazole sulphoxide levels at 24 (P <  0.001), 30 (P <  0.001) and 36 h (P <  0.01) after administration of albendazole with piperonyl butoxide, with statistically increased levels of albendazole sulphone at 24, 30 and 48 h after administration. No significance difference (P > 0.05) in values of maximum concentration (normal and calculated) could be observed between groups of goats. However, values of time to reach the concentration maximum (normal and calculated), area under the concentration–time curve (0–∞ and calculated), minimum residence time, distribution half-life, elimination half-life and total area under the first movement of plasma drug concentration–time curve were significantly higher (P <  0.05) in plasma levels of albendazole sulphoxide in goats following single oral co-administration of albendazole with piperonyl butoxide. The faecal egg count reduction and lower 95% confidence limit for the group treated with albendazole alone were 97 and 68%, while for co-administration of albendazole and piperonyl butoxide the values were 99 and 97%, respectively. The ED50 for egg hatch was 0.196, indicating suspected resistance to benzimidazole anthelmintics. The drug combination proved efficacious against an albendazole-resistant nematode parasite population in goats.

scholarly journals Pharmacokinetic and Pharmacodynamic Evaluation of Marbofloxacin in Pig against Korean Local Isolates ofActinobacillus pleuropneumoniae

2017 ◽  
Vol 2017 ◽  
pp. 1-11 ◽  
Author(s):  
Md. Akil Hossain ◽  
Hae-chul Park ◽  
Kyunghun Jeong ◽  
Yang ho Jang ◽  
Dae Gyun Kim ◽  
...  
Keyword(s):  
Body Weight ◽  
Ex Vivo ◽  
Peak Plasma ◽  
Plasma Concentrations ◽  
Antibacterial Activities ◽  
Time Intervals ◽  
Concentration Time ◽  
Elimination Half ◽  
The Mean

The pharmacokinetics of marbofloxacin in pigs after intravenous (i.v.), intramuscular (i.m.), and peroral (p.o.) administration and pharmacokinetic/pharmacodynamic indices of this drug against Korean local isolates ofActinobacillus pleuropneumoniaewere determined in this study. Marbofloxacin (2.50 mg/kg of body weight) was administered, and blood samples were collected with designated time intervals. Plasma-extracted marbofloxacin was injected into the LC-MS/MS system. The in vitro and ex vivo antibacterial activities of marbofloxacin were evaluated against 20 isolates ofA. pleuropneumoniae. The mean peak plasma concentrations (Cmax) after i.v., i.m., and p.o administration were2.60±0.10,2.59±0.12, and2.34±0.12 µg/mL at0.25±0.00,0.44±0.10, and1.58±0.40 h, respectively. The area under the plasma concentration-time curves (AUC0–24) and elimination half-lives were24.80±0.90,25.80±1.40, and23.40±5.00 h·μg/mL and8.60±0.30,12.80±1.10, and8.60±0.00 h, for i.v., i.m., and p.o. administration, correspondingly. The AUC0–24/MICs of marbofloxacin after i.v., i.m., and p.o. administration were253.86±179.91,264.1±187.16, and239.53±169.75 h, respectively. TheCmax/MIC values were26.58±18.84,26.48±18.77, and23.94±16.97, and T>MICs were42.80±1.01,36.40±1.24, and38.60±1.18 h, after i.v., i.m., and p.o. administration, respectively. Thus, marbofloxacin dosage of 2.50 mg/kg of body weight by i.v., i.m., and p.o. administration with 24 h dosing interval will provide effective treatment for the infection of pig byA. pleuropneumonia.

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 Bronchopulmonary Disposition of Intravenous Voriconazole and Anidulafungin Given in Combination to Healthy Adults

2009 ◽  
Vol 53 (12) ◽  
pp. 5102-5107 ◽  
Author(s):  
Jared L. Crandon ◽  
Mary Anne Banevicius ◽  
Annie F. Fang ◽  
Penelope H. Crownover ◽  
R. Fredrick Knauft ◽  
...  
Keyword(s):  
Drug Penetration ◽  
Total Drug ◽  
Time Curve ◽  
Minimum Effective Concentration ◽  
Epithelial Lining Fluid ◽  
Concentration Time ◽  
The Mean ◽  
Adult Volunteers ◽  
Healthy Participants ◽  
Total Concentrations

ABSTRACT Voriconazole and anidulafungin in combination are being investigated for use for the treatment of pulmonary aspergillosis. We determined the pulmonary disposition of these agents. Twenty healthy participants received intravenous voriconazole (at 6 mg/kg of body weight every 12 h [q12h] on day 1 and then at 4 mg/kg q12h) and anidulafungin (200 mg on day 1 and then 100 mg every 24 h) for 3 days. Five participants each were randomized for collection of bronchoalveolar lavage samples at times of 4, 8, 12, and 24 h. Drug penetration was determined by the ratio of the total drug area under the concentration-time curve during the dosing interval (AUC0-τ) for epithelial lining fluid (ELF) and alveolar macrophages (AM) to the total drug AUC0-τ in plasma. The mean (standard deviation) half-life and AUC0-τ were 6.9 (2.1) h and 39.5 (19.8) μg·h/ml, respectively, for voriconazole and 20.8 (3.1) h and 101 (21.8) μg·h/ml, respectively, for anidulafungin. The AUC0-τ values for ELF and AM were 282 and 178 μg·h/ml, respectively, for voriconazole, and 21.9 and 1,430 μg·h/ml, respectively, for anidulafungin. This resulted in penetration ratios into ELF and AM of 7.1 and 4.5, respectively, for voriconazole and 0.22 and 14.2, respectively, for anidulafungin. The mean total concentrations of both drugs in ELF and AM at 4, 8, 12, and 24 h remained above the MIC90/90% minimum effective concentration for most Aspergillus species. In healthy adult volunteers, voriconazole achieved high levels of exposure in both ELF and AM, while anidulafungin predominantly concentrated in AM.

scholarly journals Optimizing the Initial Amikacin Dosage in Adults

2015 ◽  
Vol 59 (11) ◽  
pp. 7094-7096 ◽  
Author(s):  
Bryan P. White ◽  
Ben Lomaestro ◽  
Manjunath P. Pai
Keyword(s):  
Body Weight ◽  
Standard Deviation ◽  
Therapeutic Drug Monitoring ◽  
Drug Concentration ◽  
Drug Monitoring ◽  
Maintenance Dose ◽  
Therapeutic Drug ◽  
High Dose ◽  
Time Curve ◽  
Concentration Time

ABSTRACTWe report on the pharmacokinetics (PK) and pharmacodynamics (PD) of high-dose (>15 mg/kg of body weight per day) amikacin. A mean (standard deviation [SD]) maximum drug concentration in the serum (Cmax) and 24-h area under the concentration-time curve (AUC24) of 101 (49.4) mg/liter and 600 (387) mg · h/liter, respectively, were observed (n= 73) with 28.0 (8.47) mg/kg/day doses. An initial amikacin dose of 2,500 mg in adults weighing 40 kg to 200 kg with therapeutic drug monitoring to adjust the maintenance dose will optimize its PK and PD.

scholarly journals Isavuconazole Pharmacodynamic Target Determination for Candida Species in anIn VivoMurine Disseminated Candidiasis Model

2013 ◽  
Vol 57 (11) ◽  
pp. 5642-5648 ◽  
Author(s):  
Alexander J. Lepak ◽  
Karen Marchillo ◽  
Jamie VanHecker ◽  
Daniel Diekema ◽  
David R. Andes
Keyword(s):  
Body Weight ◽  
Dose Range ◽  
Clinical Trial Data ◽  
Free Drug ◽  
Time Curve ◽  
Content Type ◽  
Disseminated Candidiasis ◽  
Elimination Half ◽  
The Mean ◽  
Species Specific

ABSTRACTPharmacodynamic (PD) studies with triazoles in the neutropenic murine disseminated candidiasis model have been performed extensively forCandida albicans. They have consistently shown that the pharmacodynamic index most closely correlated with efficacy is the ratio of the 24-h area under the concentration-time curve (AUC) to the MIC, and a target 24-h free-drug AUC/MIC ratio near 25 is associated with 50% of maximal microbiologic efficacy. We utilized this model to investigate the pharmacodynamics of isavuconazole. Isavuconazole pharmacokinetics were linear over the dose range studied. Oral-gastric doses of 640, 160, 40, and 10 mg of prodrug/kg of body weight produced peak levels of 0.51 to 25.4 mg/liter, an elimination half-life of 1 to 5 h, and an AUC from 0 h to infinity (AUC0-∞) of 0.9 to 287 mg · h/liter. The AUC/MIC ratio was the pharmacodynamic index that correlated best with efficacy (R2, 0.84). Pharmacodynamic target studies were performed using 4C. albicansisolates with both a 24-h and a 96-h treatment duration. The strains were chosen to include previously characterized fluconazole-resistant strains. The mean 50% effective doses (ED50) (expressed in mg/kg of body weight/12 h) and associated 24-h free-drug AUC/MIC ratios were 89.3 ± 46.7 and 67.7 ± 35 for the 24-h treatment and 59.6 ± 22 and 33.3 ± 25.5 for the 96-h treatment. These differences were not statistically significant. Pharmacodynamic targets for two non-albicans Candidaspecies were also explored. The mean ED50(expressed in mg/kg/12 h) and associated 24-h free-drug AUC/MIC ratios were 31.2 and 6.2 forCandida tropicalis(n= 1) and 50.5 and 1.6 forCandida glabrata(n= 2). These PD targets were significantly different fromC. albicanstargets (P, 0.04). Isavuconazole PD targets forC. albicansare similar to those observed in this model with other triazoles. However, the PD targets for non-albicans Candidaspecies were more than 10-fold lower than those forC. albicans(P, 0.04). This difference is similar to the species-specific PD relationships for the echinocandins. The lower PD targets for these species in this model will be important to consider in the analysis of clinical trial data and during the development of susceptibility breakpoints.

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