scholarly journals Moxifloxacin Pharmacokinetics and Pleural Fluid Penetration in Patients with Pleural Effusion

2013 ◽  
Vol 58 (3) ◽  
pp. 1315-1319 ◽  
Author(s):  
Kalliopi Chatzika ◽  
Katerina Manika ◽  
Paschalina Kontou ◽  
Georgia Pitsiou ◽  
Despina Papakosta ◽  
...  
Keyword(s):  
Pleural Effusion ◽  
Pleural Fluid ◽  
High Performance ◽  
Drug Exposure ◽  
Volume Of Distribution ◽  
Pharmacokinetic Parameters ◽  
Time Interval ◽  
Parapneumonic Effusion ◽  
Malignant Effusion ◽  
Time Curve

ABSTRACTThe aim of this study was to evaluate the pharmacokinetics and penetration of moxifloxacin (MXF) in patients with various types of pleural effusion. Twelve patients with empyema/parapneumonic effusion (PPE) and 12 patients with malignant pleural effusion were enrolled in the study. A single-dose pharmacokinetic study was performed after intravenous administration of 400 mg MXF. Serial plasma (PL) and pleural fluid (PF) samples were collected during a 24-h time interval after drug administration. The MXF concentration in PL and PF was determined by high-performance liquid chromatography, and main pharmacokinetic parameters were estimated. Penetration of MXF in PF was determined by the ratio of the area under the concentration-time curve from time zero to 24 h (AUC24) in PF (AUC24PF) to the AUC24in PL. No statistically significant differences in the pharmacokinetics in PL were observed between the two groups, despite the large interindividual variability in the volume of distribution, clearance, and elimination half-life. The maximum concentration in PF (CmaxPF) in patients with empyema/PPE was 2.23 ± 1.31 mg/liter, and it was detected 7.50 ± 2.39 h after the initiation of the infusion. In patients with malignant effusion, CmaxPFwas 2.96 ± 1.45 mg/liter, but it was observed significantly earlier, at 3.58 ± 1.38 h (P< 0.001). Both groups revealed similar values of AUC24PF(31.83 ± 23.52 versus 32.81 ± 12.66 mg · h/liter). Penetration of MXF into PF was similarly good in both patient groups (1.11 ± 0.74 versus 1.17 ± 0.39). Despite similar plasma pharmacokinetics, patients with empyema/parapneumonic effusion showed a significant delay in achievement of PF maximum MXF levels compared to those with malignant effusion. However, in both groups, the degree of MXF PF penetration and the on-site drug exposure, expressed by AUC24PF, did not differ according to the type of pleural effusion.

Pharmacokinetics of undiluted or diluted high-dose etoposide with or without busulfan administered to patients with hematologic malignancies.

1994 ◽  
Vol 12 (7) ◽  
pp. 1468-1474 ◽  
Author(s):  
K Mross ◽  
P Bewermeier ◽  
W Krüger ◽  
M Stockschläder ◽  
A Zander ◽  
...  
Keyword(s):  
High Performance ◽  
Drug Exposure ◽  
Area Under The Curve ◽  
Volume Of Distribution ◽  
Pharmacokinetic Parameters ◽  
High Dose ◽  
Pharmacokinetic Data ◽  
Blood Samples ◽  
Systemic Drug Exposure ◽  
Systemic Drug

PURPOSE We used two different methods to administer high-dose etoposide (VP-16) during a myeloablative conditioning chemotherapy regimen before bone marrow transplantation (BMT). VP-16 was administered either diluted (0.5 mg/mL) or undiluted (20 mg/mL), with or without busulfan. PATIENTS AND METHODS Blood samples were drawn from 17 patients during the infusion (6 hours) and thereafter daily until 2 days after BMT. VP-16 concentrations were measured in all plasma samples by high-performance liquid chromatography (HPLC) and electrochemical detection, and the results were analyzed with a pharmacokinetic data analysis system. RESULTS All calculated pharmacokinetic parameters in the two patient groups (VP-16 administered diluted or undiluted) were similar. There were no statistically significant differences in half-lives, mean residence time (MRT), volume of distribution, total clearance, or area under the curve (AUC). VP-16 was found in blood samples from eight of 17 patients at the time of BMT. Significant differences in systemic drug exposure and systemic clearance were found when patients were grouped according to treatment with busulfan or with total-body irradiation (TBI). CONCLUSION The two administration modes for VP-16, either diluted or undiluted, are bioequivalent in pharmacokinetic terms. The terminal half-lives were longer than expected and resulted in significant VP-16 plasma levels at the time of BMT. The biologic significance remains unclear. Busulfan and/or concomitant medication with phenytoin influence plasma clearance (clp) and systemic drug exposure significantly.

scholarly journals Pigtail Catheter Use for Draining Pleural Effusions of Various Etiologies

2012 ◽  
Vol 2012 ◽  
pp. 1-6 ◽  
Author(s):  
Adel Salah Bediwy ◽  
Hesham Galal Amer
Keyword(s):  
Pleural Effusion ◽  
Success Rate ◽  
Pleural Fluid ◽  
Tube Thoracostomy ◽  
Chest Drain ◽  
Parapneumonic Effusion ◽  
Pigtail Catheter ◽  
Efficacy And Safety ◽  
Malignant Effusion ◽  
Pleural Effusions

Background. Use of small-bore pigtail catheter is a less invasive way for draining pleural effusions than chest tube thoracostomy. Methods. Prospectively, we evaluated efficacy and safety of pigtail catheter (8.5–14 French) insertion in 51 cases of pleural effusion of various etiologies. Malignant effusion cases had pleurodesis done through the catheter. Results. Duration of drainage of pleural fluid was 3–14 days. Complications included pain (23 patients), pneumothorax (10 patients), catheter blockage (two patients), and infection (one patient). Overall success rate was 82.35% (85.71% for transudative, 83.33% for tuberculous, 81.81% for malignant, and 80% for parapneumonic effusion). Nine cases had procedure failure, five due to loculated effusions, and four due to rapid reaccumulation of fluid after catheter removal. Only two empyema cases (out of six) had a successful procedure. Conclusion. Pigtail catheter insertion is an effective and safe method of draining pleural fluid. We encourage its use for all cases of pleural effusion requiring chest drain except for empyema and other loculated effusions that yielded low success rate.

scholarly journals Linezolid Pharmacokinetics in Adult Patients with Cystic Fibrosis

2004 ◽  
Vol 48 (1) ◽  
pp. 281-284 ◽  
Author(s):  
John A. Bosso ◽  
Patrick A. Flume ◽  
Susan L. Gray
Keyword(s):  
Cystic Fibrosis ◽  
High Performance ◽  
Elimination Rate ◽  
Blood Chemistry ◽  
Volume Of Distribution ◽  
Adult Patients ◽  
Pharmacokinetic Parameters ◽  
Time Curve ◽  
Before And After ◽  
Total Body

ABSTRACT The pharmacokinetics of many drugs are altered in patients with cystic fibrosis (CF), often necessitating different dosage requirements than those used in non-CF patients. The objective of this study was to determine the pharmacokinetics of linezolid, an antibiotic with good activity against gram-positive organisms such as methicillin-resistant Staphylococcus aureus, in patients with CF so that dosage requirements could be established. Twelve adult patients (6 male) ranging in age from 22 to 39 years were studied. A single 600-mg dose was administered intravenously over 0.5 h, and plasma samples were collected at 0 (predose), 0.5, 0.75, 1, 2, 4, 8, and 24 h. Linezolid concentrations were determined with a validated high-performance liquid chromatography assay. Pharmacokinetic parameters were estimated using standard noncompartmental methods. Blood chemistry and hematologic indices were determined before and after the study for safety purposes. All patients completed the study without encountering any adverse reactions. The pharmacokinetic parameters, while variable, with half-lives varying from 1.76 to 8.36 h, were similar to those previously described in other populations. Mean (± standard deviation) values for pharmacokinetic parameters of interest were as follows: elimination rate constant, 0.21 (0.11) h−1; half-life, 4.41 (2.43); volume of distribution at steady state, 0.87 (0.19) liters/kg of body weight; and total body clearance, 0.12 (0.06) liters/h/kg. No patient would have achieved the pharmacodynamic target of an area under the concentration-time curve/MIC ratio of 83 h for pathogens for which the MIC was 4 μg/ml. Patients with inadequate clinical responses to linezolid may require more frequent dosing.

scholarly journals Population Pharmacokinetics of Liposomal Amphotericin B in Immunocompromised Children

2016 ◽  
pp. AAC.01427-16 ◽  
Author(s):  
Jodi M. Lestner ◽  
Andreas H. Groll ◽  
Ghaith Aljayyoussi ◽  
Nita L. Seibel ◽  
Aziza Shad ◽  
...  
Keyword(s):  
Amphotericin B ◽  
Liposomal Amphotericin ◽  
High Performance ◽  
Drug Exposure ◽  
Compartment Model ◽  
Invasive Fungal Disease ◽  
Volume Of Distribution ◽  
Liposomal Amphotericin B ◽  
Time Curve ◽  
Maximum Serum

BackgroundLiposomal amphotericin B (LAmB) is widely used in the treatment of invasive fungal disease (IFD) in adults and children. There are relatively limited PK data to inform optimal dosing in children that achieves systemic drug exposures comparable to those of adults.ObjectivesTo describe the pharmacokinetics of LAmB in children aged 1-17 years with suspected or documented IFD.MethodsThirty-five children were treated with LAmB at dosages of 2.5-10 mg kg-1daily. Samples were taken at baseline and at 0.5-2.0 hourly intervals for twenty-four hours after receipt of the first dose (n=35 patients) and on the final day of therapy (n=25 patients). LAmB was measured using high performance liquid chromatography (HPLC). The relationship between drug exposure and development of toxicity was explored.ResultsAn evolution in PK was observed during the course of therapy resulting in a proportion of patients (n=13) having significantly higher maximum serum concentration (Cmax) and area under the concentration time curve (AUC0-24) later in the course of therapy, without evidence of drug accumulation (Cminaccumulation ratio, AR < 1.2). The fit of a 2-compartment model incorporating weight and an exponential decay function describing volume of distribution best described the data. There was a statistically significant relationship between mean AUC0-24and probability of nephrotoxicity (OR 2.37; 95% CI 1.84-3.22, p=0.004).ConclusionsLAmB exhibits nonlinear pharmacokinetics. A third of children appear to experience a time-dependent change in PK, which is not explained by weight, maturation or observed clinical factors.

Pharmacokinetics and bioequivalence of etoposide following intravenous administration of etoposide phosphate and etoposide in patients with solid tumors.

1995 ◽  
Vol 13 (11) ◽  
pp. 2835-2841 ◽  
Author(s):  
S Kaul ◽  
L N Igwemezie ◽  
D J Stewart ◽  
S Z Fields ◽  
M Kosty ◽  
...  
Keyword(s):  
Confidence Interval ◽  
High Performance ◽  
Plasma Concentrations ◽  
Systemic Circulation ◽  
Volume Of Distribution ◽  
Pharmacokinetic Parameters ◽  
Time Curve ◽  
Etoposide Phosphate ◽  
Elimination Half ◽  
Constant Rate

PURPOSE To assess the pharmacokinetics and bioequivalence of etoposide following intravenous (i.v.) administration of etoposide phosphate (Etopophos; Bristol-Myers Squibb, Princeton, NJ), a prodrug of etoposide, and VePesid (Bristol-Myers Squibb). PATIENTS AND METHODS Forty-nine solid tumor patients were randomized to receive Etopophos or VePesid on day 1 of a day-1,3,5 schedule of treatment. The alternate drug was given on day 3 and repeated on day 5. The dose, 150 mg/m2 of etoposide equivalent, was administered by constant rate infusion over 3.5 hours. The plasma concentrations of etoposide phosphate and etoposide were determined using validated high-performance liquid chromatography (HPLC) assays. Pharmacokinetic parameters were calculated by a noncompartmental method. Etopophos was considered to be bioequivalent to VePesid if the 90% confidence limits for the differences in mean maximum concentration (Cmax) and AUCinf of etoposide were contained within 80% to 125% for the long-transformed data. RESULTS Forty-one patients were assessable for pharmacokinetics and bioequivalence assessment. Following i.v. administration, etoposide phosphate was rapidly and extensively converted to etoposide in systemic circulation, resulting in insufficient data to estimate its pharmacokinetics. The mean bioavailability of etoposide from Etopophos, relative to VePesid, was 103% (90% confidence interval, 99% to 106%) based on Cmax, and 107% (90 confidence interval, 105% to 110%) based on area under the concentration versus time curve from zero to infinity (AUCinf) values. Mean terminal elimination half-life (t1/2), steady-state volume of distribution (Vss), and total systemic clearance (CL) values of etoposide were approximately 7 hours, 7 L/m2, and 17 mL/min/m2 after Etopophos and VePesid treatments, respectively. The main toxicity observed was myelosuppression, characterized by leukopenia and neutropenia. CONCLUSION With respect to plasma levels of etoposide, i.v. Etopophos is bioequivalent to i.v. VePesid.

scholarly journals Ciprofloxacin pharmacokinetics in burn patients.

1996 ◽  
Vol 40 (5) ◽  
pp. 1153-1156 ◽  
Author(s):  
J C Garrelts ◽  
G Jost ◽  
S F Kowalsky ◽  
G J Krol ◽  
J T Lettieri
Keyword(s):  
Creatinine Clearance ◽  
High Performance ◽  
Elimination Rate ◽  
Inverse Correlation ◽  
Volume Of Distribution ◽  
Control Device ◽  
Pharmacokinetic Parameters ◽  
Burn Patients ◽  
Time Curve ◽  
Mean Values

Many drugs exhibit altered pharmacokinetic parameters in burn patients. We prospectively evaluated the pharmacokinetics of ciprofloxacin in eight burn patients with active infections. Each patient received a 400-mg dose of ciprofloxacin intravenously (i.v.) every 8 h, with each dose infused over 1 h by using a rate control device. Blood samples for analysis of plasma ciprofloxacin concentrations, determined by high-performance liquid chromatography, were obtained immediately predose, at the end of the infusion, and 1, 2, 3, 4, 5, 6, and 7 h after the end of the infusion. Urine was collected from 0 to 2, 2 to 4, and 4 to 8 h following the same dose, and an aliquot was saved for determination of the ciprofloxacin concentration. Urine was also collected for 24 h prior to this dose for measurement of creatinine clearance (CLCR). Pharmacokinetic parameters were estimated by noncompartmental analysis. Mean maximum and minimum plasma ciprofloxacin concentrations were 4.2 +/- 1.1 and 0.70 +/- 0.55 microgram/ml, respectively. Mean values for clearance (CL), renal clearance (CLR), volume of distribution, terminal elimination rate constant, half-life (t1/2), and area under the concentration-time curve (AUC) were 29.1 +/- 17.5 liters/h, 13.5 +/- 10.1 liters/h, 1.75 +/- 0.41 liters/kg, 0.222 +/- 0.098 h-1, 4.5 +/- 3.9 h, and 20.7 +/- 16.6 micrograms.h/ml, respectively. CL was higher and t1/2 was shorter than noted in previous studies of acutely ill, hospitalized patients. A good correlation was noted between creatinine clearance CL(CR) and both total ciprofloxacin CL (r = 0.85) and CLR (r = 0.84). A moderate inverse correlation was noted between percent body surface area burned and total ciprofloxacin CL (r = -0.55). An AUC/MIC ratio above 125 SIT-1 (where SIT is serum inhibitory titer), which has been strongly correlated with clinical response and time to bacterial eradication, was achieved in five of eight patients (63%) with a MIC of 0.25 microgram/ml. At a ciprofloxacin dosage of 400 mg i.v. every 12 h, an AUC/MIC ratio above 125 SIT-1 would have been achieved in only two of eight patients (25%). We conclude that ciprofloxacin CL is highly variable, but generally increased, in burn patients compared with that in acutely ill, general medical and surgical patients. Because of an increase in CL, a ciprofloxacin dosage of 400 mg i.v. every 8 h is more likely to produce the desired response in burn patients than the same dose given every 12 h.

scholarly journals Herb-Drug Interaction betweenEchinacea purpureaand Darunavir-Ritonavir in HIV-Infected Patients

2010 ◽  
Vol 55 (1) ◽  
pp. 326-330 ◽  
Author(s):  
José Moltó ◽  
Marta Valle ◽  
Cristina Miranda ◽  
Samandhy Cedeño ◽  
Eugenia Negredo ◽  
...  
Keyword(s):  
High Performance ◽  
Geometric Mean ◽  
Echinacea Purpurea ◽  
The Body ◽  
Pharmacokinetic Parameters ◽  
Root Extract ◽  
Open Label ◽  
Fixed Sequence ◽  
Time Curve ◽  
Sequence Study

ABSTRACTThe aim of this open-label, fixed-sequence study was to investigate the potential ofEchinacea purpurea, a commonly used botanical supplement, to interact with the boosted protease inhibitor darunavir-ritonavir. Fifteen HIV-infected patients receiving antiretroviral therapy including darunavir-ritonavir (600/100 mg twice daily) for at least 4 weeks were included.E. purpurearoot extract capsules were added to the antiretroviral treatment (500 mg every 6 h) from days 1 to 14. Darunavir concentrations in plasma were determined by high-performance liquid chromatography immediately before and 1, 2, 4, 6, 8, 10, and 12 h after a morning dose of darunavir-ritonavir on days 0 (darunavir-ritonavir) and 14 (darunavir-ritonavir plus echinacea). Individual darunavir pharmacokinetic parameters were calculated by noncompartmental analysis and compared between days 0 and 14 with the geometric mean ratio (GMR) and its 90% confidence interval (CI). The median age was 49 (range, 43 to 67) years, and the body mass index was 24.2 (range, 18.7 to 27.5) kg/m2. Echinacea was well tolerated, and all participants completed the study. The GMR for darunavir coadministered with echinacea relative to that for darunavir alone was 0.84 (90% CI, 0.63-1.12) for the concentration at the end of the dosing interval, 0.90 (90% CI, 0.74-1.10) for the area under the concentration-time curve from 0 to 12 h, and 0.98 (90% CI, 0.82-1.16) for the maximum concentration. In summary, coadministration ofE. purpureawith darunavir-ritonavir was safe and well tolerated. Individual patients did show a decrease in darunavir concentrations, although this did not affect the overall darunavir or ritonavir pharmacokinetics. Although no dose adjustment is required, monitoring darunavir concentrations on an individual basis may give reassurance in this setting.

scholarly journals The Differential Diagnostic Values of Cytokine Levels in Pleural Effusions

2005 ◽  
Vol 2005 (1) ◽  
pp. 2-8 ◽  
Author(s):  
Saadet Akarsu ◽  
A. Nese Citak Kurt ◽  
Yasar Dogan ◽  
Erdal Yilmaz ◽  
Ahmet Godekmerdan ◽  
...  
Keyword(s):  
Differential Diagnosis ◽  
Pleural Effusion ◽  
Pleural Fluid ◽  
Parapneumonic Effusion ◽  
Pleural Effusions ◽  
Tuberculous Pleural Effusion ◽  
Cytokine Levels ◽  
Diagnostic Values

The aim is to examine whether the changes in pleural fluid interleukin (IL)-1β, IL-2, IL-6, and IL-8 levels were significant in differential diagnosis of childhood pleural effusions. IL-1β, IL-2, IL-6, and IL-8 levels in pleural fluids of all 36 patients were measured. The levels of IL-1β, IL-2, IL-6, and IL-8 in pleural fluids were statistically significantly higher in the transudate group compared with those of the exudate group. The levels of IL-1β, IL-6, and IL-8 were also found to be statistically significantly higher in the empyema group compared with both the parapneumonic and the tuberculous pleural effusion groups. The levels of IL-2 and IL-6 were detected to be statistically significantly higher in the tuberculous pleural effusion group in comparison with those of the parapneumonic effusion group. The results showed that pleural fluids IL-1β, IL-2, IL-6, and IL-8 could be used in pleural fluids exudate and transudate distinction.

scholarly journals Pharmacokinetics of danofloxacin in African catfish (Clarias gariepinus) after intravenous and intramuscular administrations

2019 ◽  
Vol 67 (4) ◽  
pp. 602-609
Author(s):  
Mohamed Aboubakr ◽  
Ahmed Soliman
Keyword(s):  
Bacterial Infections ◽  
High Performance ◽  
Clarias Gariepinus ◽  
Volume Of Distribution ◽  
Pharmacokinetic Parameters ◽  
African Catfish ◽  
Caudal Vein ◽  
Group 2 ◽  
Total Body ◽  
The Right

The plasma pharmacokinetics of danofloxacin was studied in healthy African catfish (Clarias gariepinus) following a single intravenous (IV) and intramuscular (IM) administration of 10 mg/kg at 22 °C. Catfish were divided into two groups (each group containing 78 fish), then danofloxacin mesylate (10 mg/kg) was administered IV (into the caudal vein) in Group 1 and IM (into the right epaxial muscle) in Group 2, and blood was obtained from the caudal vein before (0 h) and after (0.25, 0.5, 1, 2, 4, 8, 12, 24, 36, 48, 72 and 96 h) of drug administration. High-performance liquid chromatography was used for the determination of plasma concentration, and a non-compartmental model was used for the analysis of pharmacokinetic parameters. After IV administration, elimination half-life (t1/2λz, 24.49 h), mean residence time (MRT, 30.14 h), volume of distribution at steady state (Vdss, 1.07 L/kg) and total body clearance (CLT, 0.035 L/h/kg) were determined. After IM administration, t1/2λz, MRT, peak concentration (Cmax), time to reach Cmax and bioavailability were 47.64 h, 61.06 h, 5.22 µg/mL, 1 h and 67.12%, respectively. After IM administration, danofloxacin showed good bioavailability and long t1/2λz. The favourable pharmacokinetic characteristics after IM administration support the use of danofloxacin for the treatment of susceptible bacterial infections in catfish.

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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