scholarly journals Intrapulmonary Pharmacokinetics of S-013420, a Novel Bicyclolide Antibacterial, in Healthy Japanese Subjects

2009 ◽  
Vol 54 (2) ◽  
pp. 866-870 ◽  
Author(s):  
Hidetoshi Furuie ◽  
Yutaka Saisho ◽  
Takayoshi Yoshikawa ◽  
Jingoro Shimada
Keyword(s):  
Maximum Concentration ◽  
High Performance ◽  
Pharmacokinetic Analysis ◽  
Pharmacokinetic Parameters ◽  
Respiratory Pathogens ◽  
Good Efficacy ◽  
Japanese Male ◽  
The Mean ◽  
Japanese Male Subjects ◽  
Tract Infections

ABSTRACT S-013420 (EDP-420) is a novel bicyclolide (bridged bicyclic macrolide) antibacterial currently under development for the treatment of respiratory tract infections. The objective of the present study was to determine the plasma and intrapulmonary pharmacokinetic parameters of orally administered S-013420 in healthy volunteers. Twenty-eight healthy Japanese male subjects who never smoked were randomly allocated to seven groups of four subjects each who underwent bronchoalveolar lavage (BAL) at different times after dosing (2, 4, 6, 8, 10, 12, or 24 h). Blood samples were also taken at 0, 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 48, and 72 h after dosing. The S-013420 concentrations in plasma, epithelial lining fluid (ELF), and alveolar macrophages (AMs) were measured by using a combined high-performance liquid chromatography-mass spectrometric technique. A pharmacokinetic analysis of the plasma, ELF, and AM S-013420 concentration profiles was performed. S-013420 was rapidly absorbed in plasma, and the mean time to the maximum concentration in plasma was 2.27 h. S-013420 was rapidly distributed to the ELF and was slowly distributed to AMs. The areas under the concentration-time curves from time zero to 24 h (AUC0-24) for S-013420 were 20.3 times higher in ELF than in plasma and 244.6 times higher in AMs than in plasma. The mean maximum concentration in plasma was higher in ELF than in plasma and was much higher in AM than in plasma. Furthermore, pharmacodynamic calculations were done by using the AUC0-24/MIC90 ratio for common pneumonia pathogens (Staphylococcus aureus, Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis). The AUC0-24 for plasma/MIC90s for these four organisms were 41.8, 83.6, 1.3, and 20.9, respectively. The AUC0-24 for ELF/MIC90s were 849.6, 1,699.2, 26.6, and 424.8, respectively. Considering the good efficacy shown in a subsequent phase 2 study (S. Kohno, K. Yamaguchi, Y. Tanigawara, A. Watanabe, A. Aoki, Y. Niki, and J. Fujita, Abstr. 47th Intersci. Conf. Antimicrob. Agents Chemother., abstr. L-485), the good distribution of S-013420 in AMs and ELF observed in the present study is predictive of the good efficacy of S-013420 against respiratory pathogens.

scholarly journals Population Pharmacokinetic Analysis of Vancomycin Using Serum Cystatin C as a Marker of Renal Function

2009 ◽  
Vol 54 (2) ◽  
pp. 778-782 ◽  
Author(s):  
Akihiro Tanaka ◽  
Tetsuya Aiba ◽  
Takashi Otsuka ◽  
Katsuya Suemaru ◽  
Tatsuya Nishimiya ◽  
...  
Keyword(s):  
Renal Function ◽  
Cystatin C ◽  
Predictive Performance ◽  
Pharmacokinetic Analysis ◽  
Pharmacokinetic Parameters ◽  
Population Pharmacokinetic ◽  
Serum Cystatin C ◽  
Serum Cystatin ◽  
New Model ◽  
The Mean

ABSTRACT We determined the population pharmacokinetics of vancomycin (VAN) using the glomerular filtration rate (GFR) estimated from the serum cystatin C concentration. We examined the predictive performance of the trough serum VAN concentration for determination of the initial dose by using a new model for the analysis of the population pharmacokinetic parameters. Data for 86 patients were used to estimate the values of the population pharmacokinetic parameters. Analysis with a nonlinear mixed-effects modeling program was done by using a one-compartment model. Data for 78 patients were used to evaluate the predictive performance of the new model for the analysis of population pharmacokinetic parameters. The estimated GFR values determined by using Hoek's formula correlated linearly with VAN clearance (VAN clearance [ml/min] = 0.825 × GFR). The mean volume of distribution was 0.864 (liters/kg). The interindividual variability of VAN clearance was 19.8%. The accuracy of the prediction determined by use of the new model was statistically better than that determined by use of the Japanese nomogram-based model because the 95% confidence interval (−3.45 to −1.38) of the difference in each value of the mean absolute error (−2.41) did not include 0. Use of the serum cystatin C concentration as a marker of renal function for prediction of serum VAN concentrations may be useful.

Comparative Pharmacokinetic of Three Sulfadiazine Suspensions by Oral Administration in Chickens

2016 ◽  
Vol 8 (2) ◽  
pp. 122
Author(s):  
Zhi-Qiang Wang ◽  
Han-Song Li ◽  
Xia Xiao ◽  
Jian-Bing Wang
Keyword(s):  
Plasma Concentration ◽  
Broiler Chickens ◽  
High Performance ◽  
Area Under The Curve ◽  
Pharmacokinetic Analysis ◽  
Pharmacokinetic Parameters ◽  
Peak Time ◽  
Comparative Pharmacokinetic ◽  
Elimination Half ◽  
Maximal Plasma

<p>The chemotherapeutics, sulfadiazine (SDA) and trimethoprim (TMP), are extensively used in a variety of animal species. In this study, a pharmacokinetic analysis was performed to compare the bioequivalence of a combined SDA and TMP product against existing licensed SDA and TMP formulations in broiler chickens. Three groups of 15 birds were administered a single dose of either the test formulation or a reference oral suspension. The plasma concentration of SDA and TMP were determined by reverse-phase high performance liquid chromatography (HPLC), and the maximal plasma concentration (C<sub>max</sub>), area under the curve (AUC), the peak time (T<sub>max</sub>), mean residence time (MRT) and elimination half-life (T<sub>1/2</sub>), were calculated for SDA. The combined formulation I and II reference suspension exhibited almost identical concentration-time curves, and ANOVA analyses of the pharmacokinetic parameters identified no significant differences between the reference preparations and the test one. Furthermore the AUC and C<sub>max</sub> values of the SDA active ingredient were not significantly different. The I formulation was bioequivalent with both II and III (80-125% and 70–143%, respectively, at the 90% confidence interval). In conclusion, the combined SDA and TMP product was bioequivalent with both existing commercially available SDA suspensions and can be used interchangeably in veterinary medical practice.</p>

scholarly journals Compartmental Pharmacokinetics of the Antifungal Echinocandin Caspofungin (MK-0991) in Rabbits

2001 ◽  
Vol 45 (2) ◽  
pp. 596-600 ◽  
Author(s):  
Andreas H. Groll ◽  
Bryan M. Gullick ◽  
Ruta Petraitiene ◽  
Vidmantas Petraitis ◽  
Myrna Candelario ◽  
...  
Keyword(s):  
High Performance ◽  
Pharmacokinetic Model ◽  
Area Under The Curve ◽  
Apparent Volume ◽  
Volume Of Distribution ◽  
Pharmacokinetic Parameters ◽  
Chromatography Method ◽  
Opportunistic Fungi ◽  
The Mean ◽  
Liquid Chromatography Method

ABSTRACT The pharmacokinetics of the antifungal echinocandin-lipopeptide caspofungin (MK-0991) in plasma were studied in groups of three healthy rabbits after single and multiple daily intravenous administration of doses of 1, 3, and 6 mg/kg of body weight. Concentrations were measured by a validated high-performance liquid chromatography method and fitted into a three-compartment open pharmacokinetic model. Across the investigated dosage range, caspofungin displayed dose-independent pharmacokinetics. Following administration over 7 days, the mean peak concentration in plasma (C max) ± standard error of the mean increased from 16.01 ± 0.61 μg/ml at the 1-mg/kg dose to 105.52 ± 8.92 μg/ml at the 6-mg/kg dose; the mean area under the curve from 0 h to infinity rose from 13.15 ± 2.37 to 158.43 ± 15.58 μg · h/ml, respectively. The mean apparent volume of distribution at steady state (Vdss) was 0.299 ± 0.011 liter/kg at the 1-mg/kg dose and 0.351 ± 0.016 liter/kg at the 6-mg/kg dose (not significant [NS]). Clearance (CL) ranged from 0.086 ± 0.017 liter/kg/h at the 1-mg/kg dose to 0.043 ± 0.004 liter/kg/h at the 6-mg/kg dose (NS), and the mean terminal half-life was between 30 and 34 h (NS). Except for a trend towards an increasedVdss, there were no significant differences in pharmacokinetic parameters in comparison to those after single-dose administration. Caspofungin was well tolerated, displayed linear pharmacokinetics that fit into a three-compartment pharmacokinetic model, and achieved sustained concentrations in plasma that were multiple times in excess of reported MICs for susceptible opportunistic fungi.

Pharmacokinetics of Tranexamic Acid in Neonates, Infants, and Children Undergoing Cardiac Surgery with Cardiopulmonary Bypass

2015 ◽  
Vol 122 (4) ◽  
pp. 746-758 ◽  
Author(s):  
Mark C. Wesley ◽  
Luis M. Pereira ◽  
Laurie A. Scharp ◽  
Sitaram M. Emani ◽  
Francis X. McGowan ◽  
...  
Keyword(s):  
Cardiopulmonary Bypass ◽  
Young Children ◽  
Tranexamic Acid ◽  
High Performance ◽  
Structural Model ◽  
Heart Defects ◽  
Circulatory Arrest ◽  
Pharmacokinetic Analysis ◽  
Pharmacokinetic Parameters ◽  
First Time

Abstract Background: Tranexamic acid (TXA) is one of the most commonly used antifibrinolytic medications in children undergoing repair of congenital heart defects. However, a pharmacokinetics analysis of TXA has never been performed in neonates or young children undergoing complex cardiac surgeries using cardiopulmonary bypass, hypothermia, circulatory arrest, and ultrafiltration. A comprehensive pharmacokinetics study was performed in this patient population. Methods: Fifty-five patients ranging from 2 days through 4 yr old were categorized into three groups: children less than 2 months old, infants 2 months to 1 yr old, and children greater than 1 yr old and weighing up to 20 kg. TXA was given as a bolus of 100 mg/kg followed by an infusion of 10 mg · kg−1 · h−1 throughout the surgery. A dose of 100 mg/kg was placed in the cardiopulmonary bypass prime. A total of 16 to 18 samples were obtained from all patients throughout surgery. Plasma TXA concentrations were measured by high-performance liquid chromatography and modeled under a nonlinear mixed-effects framework with a two-compartment structural model. Results: Cardiopulmonary bypass had a statistically significant impact on all pharmacokinetic parameters. Age was a better covariate than body weight, affecting both the distribution and the elimination of TXA. However, weight performed well in some cases. Other covariates including body surface area, pump prime volume, ultrafiltrate volume, and body temperature did not improve the model. Conclusions: This TXA pharmacokinetic analysis is reported for the first time in neonates and young children undergoing complex cardiac surgeries with cardiopulmonary bypass. Dosing recommendations are provided as guidance for maintaining desired target concentrations.

scholarly journals Joint Population Pharmacokinetic Analysis of Zidovudine, Lamivudine, and Their Active Intracellular Metabolites in HIV Patients

2011 ◽  
Vol 55 (7) ◽  
pp. 3423-3431 ◽  
Author(s):  
C. Bazzoli ◽  
H. Bénech ◽  
E. Rey ◽  
S. Retout ◽  
D. Salmon ◽  
...  
Keyword(s):  
Compartment Model ◽  
Population Pharmacokinetic Analysis ◽  
Pharmacokinetic Analysis ◽  
Pharmacokinetic Parameters ◽  
Population Pharmacokinetic ◽  
Intracellular Metabolites ◽  
Drug Concentrations ◽  
The Mean ◽  
Intracellular Concentrations ◽  
Apparent Bioavailability

ABSTRACTThe population pharmacokinetic parameters of zidovudine (AZT), lamivudine (3TC), and their active intracellular metabolites in 75 naïve HIV-infected patients receiving an oral combination of AZT and 3TC twice daily as part of their multitherapy treatment in the COPHAR2-ANRS 111 trial are described. Four blood samples per patient were taken after 2 weeks of treatment to measure drug concentrations at steady state. Plasma AZT and 3TC concentrations were measured in 73 patients, and among those, 62 patients had measurable intracellular AZT-TP and 3TC-TP concentrations. For each drug, a joint population pharmacokinetic model was developed and we investigated the influence of different covariates. We then studied correlations between the mean plasma and intracellular concentrations of each drug. A one-compartment model with first-order absorption and elimination best described the plasma AZT concentration, with an additional compartment for intracellular AZT-TP. A similar model but with zero-order absorption was found to adequately described concentrations of 3TC and its metabolite 3TC-TP. The half-lives of AZT and 3TC were 0.81 h (94.8%) and 2.97 h (39.2%), respectively, whereas the intracellular half-lives of AZT-TP and 3TC-TP were 10.73 h (69%) and 21.16 h (44%), respectively. We found particularly a gender effect on the apparent bioavailability of AZT, as well as on the mean plasma and intracellular concentrations of AZT, which were significantly higher in females than in males. Relationships between mean plasma drug and intracellular metabolite concentrations were also highlighted both for AZT and for 3TC. Simulation with the model of plasma and intracellular concentrations for once- versus twice-daily regimens suggested that a daily dosing regimen with double doses could be appropriate.

scholarly journals Pharmacokinetics of a Once-Daily Oral Dose of Moxifloxacin (Bay 12-8039), a New Enantiomerically Pure 8-Methoxy Quinolone

1999 ◽  
Vol 43 (11) ◽  
pp. 2793-2797 ◽  
Author(s):  
John T. Sullivan ◽  
Marilyn Woodruff ◽  
John Lettieri ◽  
Vipin Agarwal ◽  
George J. Krol ◽  
...  
Keyword(s):  
High Performance ◽  
Vital Signs ◽  
Blood Chemistry ◽  
Controlled Study ◽  
Pharmacokinetic Parameters ◽  
Fluorometric Detection ◽  
Double Blind ◽  
Time Curve ◽  
Once Daily ◽  
The Mean

ABSTRACT The pharmacokinetics, safety, and tolerability of oral moxifloxacin, a new 8-methoxy quinolone, were assessed in a randomized, double-blind, placebo-controlled study in which healthy male and female volunteers received either 400 mg of moxifloxacin once daily (n = 10) or a placebo once daily (n = 5) for 10 days. Plasma moxifloxacin concentrations on days 1 and 10 were measured by high-performance liquid chromatography and fluorometric detection. Standard pharmacokinetic parameters were estimated by noncompartmental methods. Natural logarithmic estimates for each pharmacokinetic variable of each subject were analyzed by a two-way analysis of variance. Hematology, blood chemistry, vital signs, and adverse events were monitored, and electrocardiograms (ECG) were performed. Plasma moxifloxacin concentrations of predicted therapeutic relevance were achieved in this study. For day 1, the mean maximum concentration of drug in serum (C max) and the area under the concentration-time curve from 0 to 24 h (AUC0–24) were 3.4 mg/liter and 30.2 mg · h/liter, respectively. Corresponding means on day 10 were 4.5 mg/liter and 48 mg · h/liter, respectively. On day 10, the mean elimination half-life was approximately 12 h. Plasma moxifloxacin concentrations exceeded the MIC for Streptococcus pneumoniae throughout the 24-h dosing period. The day 1 and day 10 mean AUC/MIC ratios were 121 and 192, respectively, and the meanC max/MIC ratios were 13 and 18, respectively. Moxifloxacin was well tolerated; no clinically relevant changes in the standard laboratory tests, vital signs, or ECG were observed. Pharmacokinetic parameters demonstrated linearity, and estimates of pharmacokinetic/pharmacodynamic ratios (AUC/MIC andC max/MIC) indicate that the regimen of 400-mg once daily should be effective for treating a variety of infections. Moxifloxacin was found to be safe and well tolerated in healthy volunteers when it was given as a single daily 400-mg dose for 10 days.

scholarly journals Modest but Variable Effect of Rifampin on Steady-State Plasma Pharmacokinetics of Efavirenz in Healthy African-American and Caucasian Volunteers

2011 ◽  
Vol 55 (7) ◽  
pp. 3527-3533 ◽  
Author(s):  
Awewura Kwara ◽  
Karen T. Tashima ◽  
Julie B. Dumond ◽  
Pamela Poethke ◽  
Jaclyn Kurpewski ◽  
...  
Keyword(s):  
Body Weight ◽  
High Performance ◽  
Geometric Mean ◽  
Pharmacokinetic Analysis ◽  
Pharmacokinetic Parameters ◽  
Pharmacokinetic Data ◽  
Time Curve ◽  
Variable Effect ◽  
Coefficients Of Variation ◽  
Tuberculosis Therapy

ABSTRACTEfavirenz-based antiretroviral regimen is preferred during rifampin-containing tuberculosis therapy. However, current pharmacokinetic data are insufficient to guide optimized concurrent dosing. This study aimed to better characterize the effects of rifampin on efavirenz pharmacokinetics. Subjects were randomized to receive 600 mg efavirenz/day or 600 mg efavirenz with 600 mg rifampin/day for 8 days, with plasma samples collected for pharmacokinetic analysis over 24 h on day 8. Treatments were then crossed over after at least a 2-week washout period, and procedures were repeated. Efavirenz concentrations were determined by high-performance liquid chromatography (HPLC), and pharmacokinetic parameters were estimated by noncompartmental analysis. Efavirenz pharmacokinetic differences between treatment periods were evaluated by pairedttest. The coefficients of variation in efavirenz plasma AUC0-24(area under the concentration-time curve from 0 to 24 h) were 50% and 56% in the absence and presence of rifampin, respectively. Of the 11 evaluable subjects (6 white, 5 black; 6 women, 5 men), the geometric mean AUC0-24ratio on/off rifampin (90% confidence interval) was 0.82 (0.72, 0.92), with individual AUC0-24ratios varying from 0.55 to 1.18. Five subjects had a 24-hour efavirenz concentration (C24) of <1,000 ng/ml on rifampin. They were more likely to have received a lower dose in milligrams/kilogram of body weight and to have lower efavirenz AUC0-24values in the basal state. Although rifampin resulted in a modest reduction in efavirenz plasma exposure in subjects as a whole, there was high variability in responses between subjects, suggesting that efavirenz dose adjustment with rifampin may need to be individualized. Body weight and genetic factors will be important covariates in dosing algorithms.

scholarly journals Pharmacokinetic Analysis of Epithelial/Endothelial Cell Barriers in Microfluidic Bilayer Devices with an Air–Liquid Interface

Micromachines ◽  
2020 ◽  
Vol 11 (5) ◽  
pp. 536
Author(s):  
Timothy S. Frost ◽  
Linan Jiang ◽  
Yitshak Zohar
Keyword(s):  
Endothelial Cell ◽  
Maximum Concentration ◽  
Molecular Size ◽  
Microfluidic Devices ◽  
Liquid Interface ◽  
Pharmacokinetic Analysis ◽  
Pharmacokinetic Parameters ◽  
Small Airways ◽  
Air Liquid Interface ◽  
Bilayer Devices

As the range of applications of organs-on-chips is broadening, the evaluation of aerosol-based therapies using a lung-on-a-chip model has become an attractive approach. Inhalation therapies are not only minimally invasive but also provide optimal pharmacokinetic conditions for drug absorption. As drug development evolves, it is likely that better screening through use of organs-on-chips can significantly save time and cost. In this work, bio-aerosols of various compounds including insulin were generated using a jet nebulizer. The aerosol flows were driven through microfluidic bilayer devices establishing an air–liquid interface to mimic the blood–air barrier in human small airways. The aerosol flow in the microfluidic devices has been characterized and adjusted to closely match physiological values. The permeability of several compounds, including paracellular and transcellular biomarkers, across epithelial/endothelial cell barriers was measured. Concentration–time plots were established in microfluidic devices with and without cells; the curves were then utilized to extract standard pharmacokinetic parameters such as the area under the curve, maximum concentration, and time to maximum concentration. The cell barrier significantly affected the measured pharmacokinetic parameters, as compound absorption through the barrier decreases with its increasing molecular size. Aerosolizing insulin can lead to the formation of fibrils, prior to its entry to the microfluidic device, with a substantially larger apparent molecular size effectively blocking its paracellular transport. The results demonstrate the advantage of using lung-on-a-chip for drug discovery with applications such as development of novel inhaled therapies.

scholarly journals Pharmacokinetics of Ciprofloxacin in the Human Eye: a Clinical Study and Population Pharmacokinetic Analysis

2000 ◽  
Vol 44 (6) ◽  
pp. 1674-1679 ◽  
Author(s):  
Nigel Morlet ◽  
Garry G. Graham ◽  
Barrie Gatus ◽  
Andrew J. McLachlan ◽  
Chris Salonikas ◽  
...  
Keyword(s):  
High Performance ◽  
Population Pharmacokinetic Analysis ◽  
Pharmacokinetic Analysis ◽  
Population Pharmacokinetic ◽  
Ocular Surgery ◽  
Human Eye ◽  
Number Of Patients ◽  
The Mean ◽  
Oral Ciprofloxacin ◽  
Oral Doses

ABSTRACT Ciprofloxacin, a fluoroquinolone antibiotic active against a wide variety of bacteria, is one of a few antibiotics which enters the human eye after oral administration. However, little is known about its pharmacokinetics in the human eye. One or two oral doses of 750 mg of ciprofloxacin (at a 12-h interval) were administered to 48 patients at various times prior to ocular surgery. Clotted blood, aqueous, and vitreous were collected at surgery, and the concentrations of ciprofloxacin were assayed by high-performance liquid chromatography. Our data were combined with those of others, and a population pharmacokinetic analysis was conducted. The concentrations of ciprofloxacin in both aqueous and vitreous were lower than those in serum and peaked at a later time. The pharmacokinetics of ciprofloxacin in aqueous and vitreous were fitted to a compartmental model in which the antibiotic was transferred into and out of the two compartments (aqueous and vitreous) by first-order processes. Population pharmacokinetic software, P-Pharm, was used to calculate the mean half-lives of the loss of ciprofloxacin from aqueous and vitreous, which were 3.5 and 5.3 h, respectively. At steady state, the mean ratios of then concentrations in aqueous and vitreous to the concentrations in serum were 23 and 17%, respectively. After the administration of one or two doses of 750 mg of ciprofloxacin, the concentrations in both aqueous and vitreous in a number of patients were lower than the MICs at which 90% of isolates are inhibited (0.5 mg/liter) for common intraocular bacterial pathogens. Simulations of concentrations in the eye after the administration of higher doses (1,500 mg of ciprofloxacin as a single dose, two doses of 750 mg 2 h apart, and 750 mg every 6 h) indicated that in approximately 20% of patients the concentrations would still be below 0.5 mg/liter. Although oral ciprofloxacin may be a beneficial adjunctive therapy, the use of oral ciprofloxacin alone may not be adequate for perioperative prophylaxis or for treatment of bacterial endophthalmitis.

scholarly journals Pharmacokinetics of Ganciclovir during Continuous Venovenous Hemodiafiltration in Critically Ill Patients

2013 ◽  
Vol 58 (1) ◽  
pp. 94-101 ◽  
Author(s):  
Thomas Horvatits ◽  
Reinhard Kitzberger ◽  
Andreas Drolz ◽  
Christian Zauner ◽  
Walter Jäger ◽  
...  
Keyword(s):  
Critically Ill ◽  
Critically Ill Patients ◽  
High Performance ◽  
Area Under The Curve ◽  
Antiviral Agent ◽  
Pharmacokinetic Analysis ◽  
Pharmacokinetic Parameters ◽  
Population Pharmacokinetic ◽  
Target Area ◽  
Continuous Venovenous Hemodiafiltration

ABSTRACTGanciclovir is an antiviral agent that is frequently used in critically ill patients with cytomegalovirus (CMV) infections. Continuous venovenous hemodiafiltration (CVVHDF) is a common extracorporeal renal replacement therapy in intensive care unit patients. The aim of this study was to investigate the pharmacokinetics of ganciclovir in anuric patients undergoing CVVHDF. Population pharmacokinetic analysis was performed for nine critically ill patients with proven or suspected CMV infection who were undergoing CVVHDF. All patients received a single dose of ganciclovir at 5 mg/kg of body weight intravenously. Serum and ultradiafiltrate concentrations were assessed by high-performance liquid chromatography, and these data were used for pharmacokinetic analysis. Mean peak and trough prefilter ganciclovir concentrations were 11.8 ± 3.5 mg/liter and 2.4 ± 0.7 mg/liter, respectively. The pharmacokinetic parameters elimination half-life (24.2 ± 7.6 h), volume of distribution (81.2 ± 38.3 liters), sieving coefficient (0.76 ± 0.1), total clearance (2.7 ± 1.2 liters/h), and clearance of CVVHDF (1.5 ± 0.2 liters/h) were determined. Based on population pharmacokinetic simulations with respect to a target area under the curve (AUC) of 50 mg · h/liter and a trough level of 2 mg/liter, a ganciclovir dose of 2.5 mg/kg once daily seems to be adequate for anuric critically ill patients during CVVHDF.

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