当前位置:首页 >> 药学 >>

Linezolid Pharmacokinetics in Adult Patients with Cystic Fibrosis

Linezolid Pharmacokinetics in Adult Patients with Cystic Fibrosis
John A. Bosso, Patrick A. Flume and Susan L. Gray Antimicrob. Agents Chemother. 2004, 48(1):281. DOI: 10.1128/AAC.48.1.281-284.2004.

Updated information and services can be found at: http://aac.asm.org/content/48/1/281 Downloaded from http://aac.asm.org/ on April 10, 2014 by guest These include:

This article cites 19 articles, 8 of which can be accessed free at: http://aac.asm.org/content/48/1/281#ref-list-1 Receive: RSS Feeds, eTOCs, free email alerts (when new articles cite this article), more?


Information about commercial reprint orders: http://journals.asm.org/site/misc/reprints.xhtml To subscribe to to another ASM Journal go to: http://journals.asm.org/site/subscriptions/

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, Jan. 2004, p. 281–284 0066-4804/04/$08.00?0 DOI: 10.1128/AAC.48.1.281–284.2004 Copyright ? 2004, American Society for Microbiology. All Rights Reserved.

Vol. 48, No. 1

Linezolid Pharmacokinetics in Adult Patients with Cystic Fibrosis
John A. Bosso,1* Patrick A. Flume,2 and Susan L. Gray2
Department of Pharmaceutical Sciences, College of Pharmacy,1 and Department of Medicine,2 Medical University of South Carolina, Charleston, South Carolina
Received 24 March 2003/Returned for modi?cation 11 August 2003/Accepted 25 September 2003

The pharmacokinetics of many drugs are altered in patients with cystic ?brosis (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 ?g/ml. Patients with inadequate clinical responses to linezolid may require more frequent dosing.

Downloaded from http://aac.asm.org/ on April 10, 2014 by guest

Most morbidity and mortality associated with cystic ?brosis (CF) is due to the pulmonary component, which is characterized by infection with such pathogens as Pseudomonas aeruginosa, Haemophilus in?uenzae, and Staphylococcus aureus and subsequent in?ammation (5). Treatment with antibiotics is considered standard care for exacerbations of pulmonary infections. Methicillin-resistant S. aureus (MRSA), which has become common in hospitals since the 1980s, is now more commonly seen in patients with CF (18). MRSA is typically treated with vancomycin, but with the advent of strains with decreased susceptibility (7) and, more recently, outright resistance (2), alternatives to this agent are needed. Because of its marked in vitro activity against the common gram-positive pathogens (9, 20), including MRSA (19), and penetration into pulmonary ?uid (3), the oxazolidinone antibiotic linezolid represents a potential therapeutic option for this disease. The pharmacokinetics of a wide variety of drugs have been demonstrated to be altered in patients with CF (12). Drugs eliminated either unchanged by the kidneys (e.g., aminoglycosides) or through metabolism by the liver (e.g., sulfamethoxazole) may have altered disposition. To date, no uni?ed explanation of altered pharmacokinetics with CF has emerged. Altered renal clearance, enhanced metabolism, and varying distribution volumes are all possibilities, depending on the drug in question. Because the pharmacokinetic differences can be dramatic enough in some cases to justify altered dosing and because such changes are unpredictable, it is necessary to de* Corresponding author. Mailing address: Medical University of South Carolina College of Pharmacy, 280 Calhoun Street, Charleston, SC 29425. Phone: (843) 792-8501. Fax: (843) 792-1712. E-mail: bossoja @musc.edu. 281

termine the pharmacokinetics of any drug that might be used in this population so that the optimal dosage regimen can be designed. The objective of this study was to characterize the pharmacokinetics of linezolid in patients with CF so that appropriate dosing recommendations could be derived.
MATERIALS AND METHODS Subjects. Adult patients of either sex who were admitted to the hospital for treatment of an acute pulmonary exacerbation of CF were invited to participate in the study, which had been approved by the local Institutional Review Board. A diagnosis of CF was documented in these patients either with two positive sweat tests or through genetic testing. Written informed consent was obtained from each subject. Patients with clinical or laboratory evidence of signi?cant renal (estimated creatinine clearance of ?30 ml/min) or hepatic (Child-Pugh class A or greater) impairment or a history of allergy to linezolid or who were receiving monoamine oxidase inhibitors were excluded. Further, a pregnancy test was performed on all female subjects of childbearing potential, and negative pregnancy status was con?rmed. Pregnant females were excluded. Demographic information and results of admission pulmonary function testing (forced expiratory volume in one second [FEV1]) were recorded. All medications being taken by the subjects immediately prior to or during the study were also noted in the study record. Study design. Information collected regarding all subjects included age, gender, weight, concurrent medications, and ?uid intake and output during the period of study. All subjects received a single, 600-mg intravenous dose of linezolid (supplied as premixed intravenous bags) administered as a one-halfhour infusion delivered by a programmable infusion pump. Blood samples were collected immediately before the drug infusion (time zero) and at 0.5 (immediately at the end of the drug infusion), 0.75, 1, 2, 4, 8, and 24 h. The exact time each specimen was collected was noted. Plasma was immediately harvested and then frozen at ?70°C until the time of assay (stability at ?70°C is ?1 year). The exact times of the dosage infusions were recorded, and a sample from the dosage container was obtained for later determination of the linezolid concentration so that the exact dose administered could be determined. Serum chemistries and hematology (complete blood count and white cell differential) were assessed within 24 h prior to the study and within 48 h poststudy to assess potential side effects of the drug.



ANTIMICROB. AGENTS CHEMOTHER. TABLE 1. Demographic characteristics of CF patients in this study
Patient Sexb Age (yr) Weight (kg) Creatinine concn in serum (mg/dl) FEV1a (liter) FEV1a (% predicted)

Drug assay. The concentrations of linezolid in plasma and in the administered drug solution were determined by the Pharmacokinetics Laboratory at the National Jewish Medical & Research Center (Denver, Colo.) with a validated, reversephase high-performance liquid chromatographic (HPLC) method. Brie?y, the samples were assessed with a system consisting of a model 515 HPLC pump, model 680 gradient controller and solvent select valve (Waters Inc., Milford, Mass.), model 8875 ?xed volume autosampler (Spectra Physics, San Jose, Calif.), model 486 UV light detectors (Waters), Macintosh 7100 computer (Apple Computers, Inc., Cupertino, Calif.), and Dynamax HPLC data management system (Ranin, Woburn, Mass.). The ?ve-point standard curve (weighted as 1/y2) ranged from 0.5 to 30 ?g/ml, and the assay precision across all concentrations was ?4.4%. Pharmacokinetic analysis. Pharmacokinetic parameters were determined using standard noncompartmental methods (6). The terminal elimination rate constant (kel) was determined by linear regression of the ?nal linear portion of the natural log of the concentration-time curve for concentrations in plasma. This analysis included at least ?ve data points. The area under the concentrationtime curve (AUC0-?) was determined with the linear trapezoidal rule, with the area from the last measurable concentration in plasma to in?nity determined as that concentration divided by kel. Peak concentrations in plasma were determined by visual inspection of the concentration-time pro?les. The parameters of interest from all patients were used to generate mean, median, and standard deviation (SD) values. Correlations between pharmacokinetic parameters and patient age and FEV1 were examined using Spearman rank correlation.

1 2 3 4 5 6 7 8 9 10 11 12
a b


37 25 29 23 22 22 22 39 28 34 39 24

54.5 57.4 63.6 46.6 57.3 48.2 38.2 89.1 58.2 55.5 66.8 40.9

1.7 0.8 0.9 0.6 0.7 0.7 0.7 1.1 0.6 0.7 1.0 0.4

0.89 1.08 1.46 2.35 2.16 2.16 1.67 2.17 1.55 0.85 3.09 0.55

25 25 36 81 69 71 60 50 50 23 78 19

Downloaded from http://aac.asm.org/ on April 10, 2014 by guest

FEV1, forced expiratory volume in one second. M, male; F, female.

RESULTS All 12 subjects completed the study successfully. The studied population consisted of six males and six females ranging in age from 22 to 39 years. Patient characteristics, including pulmonary function status as re?ected by FEV1, are displayed in Table 1. Concomitant medications that the patients were receiving at the time of or just prior to the study included inhaled and systemic antibiotics (tobramycin, vancomycin, piperacillintazobactam, azithromycin, ceftazidime, amoxicillin-clavulanate, cefepime, and cipro?oxacin); systemic, inhaled, and nasal corticosteroids (prednisone and ?uticasone); pancreatic enzymes; inhaled and systemic bronchodilators (albuterol and ipratropium); rofecoxib; vitamins; iron; narcotic analgesics; megestrol; dronabinol; proton pump inhibitors (lansoprazole and omeprazole); insulin; inhaled rhDNase; cetirizine; ursodiol; ranitidine; and antidepressants (paroxetine, ?uoxetine, and sertraline). Pharmacokinetics. The pharmacokinetic parameter estimates varied widely between patients, although mean values were similar to those reported for adults elsewhere in the literature. For example, elimination half-lives varied from ?2 to ?8 h. Individual and mean values for all pharmacokinetic parameters of interest are listed in Table 2. No correlation between pharmacokinetic characteristics and either patient age or disease status (FEV1) was found. Mean (?SD) concentrations in plasma for all patients are shown in Fig. 1. Seven of the 12 patients had undetectable concentrations of linezolid at the 24-h sampling point. Safety. No clinically evident adverse effects were noted during the infusion or over the period of sample collection. Further, no adverse effects as noted by laboratory tests were detected. DISCUSSION The pharmacokinetics of a number of drugs, mostly antibiotics, have been shown to vary in patients with CF. Aminoglycosides, which are chie?y eliminated by the kidneys, vary markedly in their elimination pharmacokinetics in CF patients.

Clearance is commonly increased, and the apparent volume of distribution may be greater as well (12), resulting in the need for higher-than-normal doses. The variability observed requires careful monitoring of concentrations in individual patients with CF to optimize ef?cacy and avoid toxicity. Drugs eliminated by metabolism may also exhibit altered disposition in this population. For example, both sulfamethoxazole and theophylline have been demonstrated to exhibit increased clearance in patients with CF (8, 11). No one explanation has emerged for these changes, although it has recently been suggested that for at least some drugs for which enhanced clearance is associated with increased renal clearance the changes may be explained by increased expression of P-glycoprotein and a resultant increase in tubular secretion (17). Thus, pharmacokinetic studies are often performed on drugs with potential therapeutic utility in CF to establish appropriate dosing guidelines. Because S. aureus plays an important role in the pathophysiology of CF airways disease, drugs such as linezolid, with good gram-positive activity in general and additional activity against MRSA in particular, will be considered for use. At least one report of successful therapeutic use has already appeared in the literature (4). In that report, MRSA was cultured from the sputum of the 24-year-old patient and was no longer detected after a 30-day course of linezolid given intravenously for 6 days and then orally for another 24 days. The 600-mg intravenous and oral doses produced similar peak and trough concentrations, suggesting good gastrointestinal absorption. The results of the present study should be viewed in the light of previously published studies of linezolid disposition, which are numerous. The drug is chie?y cleared by nonrenal mechanisms, with only 30% of a dose appearing in the urine as unchanged drug (16). Fifty percent is accounted for as two major metabolites, also found in the urine. Total and renal clearances have been reported as 120 and 50 ml/min, respectively (D. J. Stalker, C. P. Wasjszczuk, and D. H. Batts, Abstr. 37th Intersci. Conf. Antimicrob. Agents Chemother., abstr. A-115 and A-116, 1997). In healthy adult subjects, the reported mean half-life has ranged from 4.4 to 6.9 h with both singledose and steady-state conditions (3, 14, 16; Stalker et al., 37th ICAAC, abstr. A-115 and A-116). Although linear elimination

VOL. 48, 2004




kel (h?1)

t1/2 (h)

Cmax (?g/ml)

AUC0–? (?g ? h/ml)

AUC0–?/MIC ratiob

VSS (liters/kg)

ClT (liters/ h/kg)

1 2 3 4 5 6 7 8 9 10 11 12 Mean SD Median

0.08 0.26 0.09 0.19 0.32 0.19 0.39 0.17 0.17 0.17 0.08 0.31 0.20 0.10 0.18

8.36 2.68 7.98 3.63 2.20 3.60 1.76 4.11 4.01 3.99 8.36 2.25 4.41 2.43 3.81

17.36 17.31 21.57 20.41 22.00 25.49 25.30 13.02 27.03 21.63 16.94 28.36 21.37 4.64 21.60

208.94 65.20 167.53 108.78 66.21 135.71 68.71 69.89 113.42 99.91 155.14 86.76 112.18 46.35 104.34

52.24 16.30 41.88 27.20 16.55 33.93 17.18 17.47 28.36 24.98 38.79 22.19 28.09 11.57 26.09

0.95 0.81 0.87 1.32 0.68 0.95 0.94 0.70 0.65 0.79 1.06 0.77 0.87 0.19 0.84

0.06 0.16 0.05 0.12 0.16 0.09 0.25 0.10 0.10 0.12 0.06 0.18 0.12 0.06 0.11

Downloaded from http://aac.asm.org/ on April 10, 2014 by guest

a t1/2, half-life; AUC0–?, area under the concentration in plasma versus the time curve from time 0 to in?nity; VSS, steady-state volume of distribution; ClT, total body clearance; Cmax, maximum observed concentration in plasma. b Theoretical value based on a MIC of 4 ?g/ml.

had been reported initially (Stalker et al., 37th ICAAC, abstr. A-115 and A-116), subsequent studies by two different investigative groups provided evidence of nonlinear elimination, which probably re?ects the saturability of one of the two major metabolic pathways for the drug (13; B. Cirincione, L. Phillips, T. Grasela, D. Stalker, and G. Jungbluth, Abstr. 39th Intersci. Conf. Antimicrob. Agents Chemother., abstr. 1205, 1999). This ?nding may explain the wide range of reported half-lives and clearance values in healthy adults. Neither age nor sex is associated with suf?cient variation of linezolid disposition in adults to warrant dosage adjustment (15). However, higher estimates of both total clearance and apparent volume of distribution were observed in a single-dose pharmacokinetic study in children 3 months to 16 years of age (10). Based on those ?ndings, a dose of 10 mg/kg administered two to three times daily was recommended. Lastly, studies in patients with mild hepatic impairment and renal dysfunction (creatinine clear-

ance as low as 10 ml/min) revealed insuf?cient alterations in pharmacokinetics to justify dosage adjustments (P. E. Hendershot, G. L. Jungbluth, S. K. Cammarata, and N. K. Hopkins, Abstr. 21st Int. Congr. Chemother., 1999; M. E. Brier, D. J. Stalker, G. R. Aronoff, D. H. Batts, K. K. Ryan, M. A. O’Grady, and N. K. Hopkins, Abstr. 38th Intersci. Conf. Antimicrob. Agents Chemother., abstr. A-54, 1998). In the present study of adults with CF, we noted marked variation in pharmacokinetic parameters. It might be that potential drug interactions in?uenced the variability we observed (e.g., with serotonin reuptake inhibitors), but this possibility could not be assessed in a single-dose study. Regardless, the extremes of the observed pharmacokinetic values were within the ranges already reported for healthy adults in the publications cited above. Nonetheless, this variability may have implications for proper dosing in the CF population. There are reasons to question the universal adequacy of a

FIG. 1. Mean (?SD) concentrations of linezolid in plasma versus time.



2. Centers for Disease Control and Prevention. 2002. Staphylococcus aureus resistant to vancomycin—United States, 2002. Morb. Mortal. Wkly. Rep. 51:565–567. 3. Conte, J. E., Jr., J. A. Golden, J. Kipps, and E. Zurlinden. 2002. Intrapulmonary pharmacokinetics of linezolid. Antimicrob. Agents Chemother. 46: 1475–1480. 4. Ferrin, M., J. B. Zuckerman, A. Meagher, and E. A. Blumberg. 2002. Successful treatment of methicillin-resistant Staphylococcus aureus pulmonary infection with linezolid in a patient with cystic ?brosis. Pediatr. Pulmonol. 33:221–223. 5. FitzSimmons, S. C. 1993. The changing epidemiology of cystic ?brosis. J. Pediatr. 122:1–9. 6. Gibaldi, M., and D. Perrier. 1982. Pharmacokinetics. Marcel Dekker, Inc., New York, N.Y. 7. Hiramatsu, K., H. Hanaki, T. Ino, K. Yabuta, T. Oguri, and F. C. Tenover. 1997. Methicillin-resistant Staphylococcus aureus clinical strain with reduced vancomycin susceptibility. J. Antimicrob. Chemother. 40:135–136. 8. Hutabarat, R. M., J. D. Unadkat, C. Sahajawalla, S. McNamara, B. Ramsey, and A. L. Smith. 1991. Disposition of drugs in cystic ?brosis. I. Sulfamethoxazole and trimethoprim. Clin. Pharmacol. Ther. 49:402–409. 9. Jones, R. N., D. M. Johnson, and M. E. Erwin. 1996. In vitro antimicrobial activities and spectra of U-100592 and U-100766, two novel ?uorinated oxazolidinones. Antimicrob. Agents Chemother. 40:720–726. 10. Kearns, G. L., S. M. Abdel-Rahman, J. L. Blumer, M. D. Reed, L. P. James, R. F. Jacobs, I. R. Welshman, G. L. Jungbluth, and D. J. Stalker. 2000. Single dose pharmacokinetics of linezolid in infants and children. Pediatr. Infect. Dis. J. 19:1178–1184. 11. Knoppert, D. C., M. Spino, R. Beck, J. J. Thiessen, and S. M. MacLeod. 1988. Cystic ?brosis: enhanced theophylline metabolism may be linked to the disease. Clin. Pharmacol. Ther. 44:254–264. 12. Lindsay, C. A., and J. A. Bosso. 1993. Optimization of antibiotic therapy in cystic ?brosis patients. Clin. Pharmacokinet. 24:496–506. 13. Meagher, A. K., A. Forrest, C. R. Rayner, M. C. Birmingham, and J. R. Schentag. 2003. Population pharmacokinetics of linezolid in patients treated in a compassionate use program. Antimicrob. Agents Chemother. 47:548– 553. 14. Sisson, T. L., G. L. Jungbluth, and N. K. Hopkins. 1999. A pharmacokinetic evaluation of concomitant administration of linezolid and aztreonam. J. Clin. Pharmacol. 39:1277–1282. 15. Sisson, T. L., G. L. Jungbluth, and N. K. Hopkins. 2002. Age and sex effects on the pharmacokinetics of linezolid. Eur. J. Clin. Pharmacol. 57:793–797. 16. Slatter, J. G., D. J. Stalker, K. L. Feenstra, I. R. Welshman, J. B. Bruss, J. P. Sams, J. G. Johnson, P. E. Sanders, M. J. Jauer, P. E. Fagerness, R. P. Stryd, G. W. Peng, and E. M. Shobe. 2001. Pharmacokinetics, metabolism, and excretion of linezolid following an oral dose of [14C]linezolid to healthy human subjects. Drug Metab. Dispos. 29:1136–1145. 17. Susanto, M., and L. Z. Benet. 2002. Can the enhanced renal clearance of antibiotics in cystic ?brosis patients be explained by P-glycoprotein transport? Pharmacol. Res. 19:457–462. 18. Thomas, S. R., K. M. Gyi, H. Gaya, and M. E. Hodson. 1998. Methicillin resistant Staphylococcus aureus: impact at a national cystic ?brosis centre. J. Hosp. Infect. 40:203–209. 19. Wootton, M., R. A. Howe, T. R. Walsh, P. M. Bennett, and A. P. MacGowan. 2002. In vitro activity of 21 antimicrobials against vancomycin-resistant Staphylococcus aureus (VRSA) and heteroVRSA (hVRSA). J. Antimicrob. Chemother. 50:755–766. 20. Zurenko, G. E., B. H. Yagi, R. D. Schaadt, J. W. Allison, J. O. Kilburn, S. E. Glickman, et al. 1996. In vitro activities of U-100592 and U-100766, novel oxazolidinone antibacterial agents. Antimicrob. Agents Chemother. 40:839– 845.

600-mg dose administered twice daily in the CF population. Pharmacodynamic studies in both humans and animals suggest that the AUC0?24 h/MIC ratio may be the parameter best correlated with antimicrobial effect (1; B. Cirincione, T. Grasela, S. Ardella, E. Ludwig, D. Stalker, B. Harkin, J. Bruss, and E. Antal., Abstr. 40th Intersci. Conf. Antimicrob. Agents Chemother., abstr. 1389, 2000; C. R. Rayner, A. Forrest, A. K. Meagher, and M. C. Birmingham, Abstr. 40th Intersci. Conf. Antimicrob. Agents Chemother., abstr. 1390, 2001). These same studies suggest a target AUC0?24 h/MIC ratio of 83 to 100 h. Based upon our data, the standard 600-mg dose would not appear to achieve an AUC0?24/MIC ratio in this range for the least susceptible staphylococcal isolates considered susceptible to linezolid (4 ?g/ml). While this is a worst-case scenario, even patients with isolates for which MICs are 1 or 2 might fail to achieve this pharmacodynamic target (see Table 2). The second reason that a 600-mg twice-daily dose may not be appropriate for all patients relates to the typical body habitus of CF patients. As is usual for CF patients, most of our patients weighed less than their ideal body weight based on height. Further, as all patients received the same dose, it is not surprising that the maximum observed concentrations in plasma were higher in patients with low body weight (range, 13 to 28.4 mg/liter), which may be explained by the fact that a standard 600-mg dose represents weight-normalized doses varying from 7 to 17 mg/kg. Higher observed concentrations and longer half-lives could have implications for the clinical safety of this agent. Thus, in patients with an inadequate clinical response with a standard dosage, a 600-mg three-times-per-day dosage regimen might be appropriate, but again, the possibility for nonlinear pharmacokinetics of the drug must be kept in mind. One would predict disproportional changes in the concentrations in plasma as doses were increased, at least in some patients. Unless monitoring of the concentrations of linezolid in plasma becomes commonplace or until the population models for nonlinear pharmacokinetics are proven appropriate for CF patients, one should use doses above the usual 600-mg twicedaily dose with caution because of the risk of hematologic and other side effects.
ACKNOWLEDGMENT This work was supported, in part, by a grant from the Pharmacia Corporation, Kalamazoo, Michigan.
REFERENCES 1. Andes, D., M. L. van Ogtrop, J. Peng, and W. A. Craig. 2002. In vivo pharmacodynamics of a new oxazolidinone (linezolid). Antimicrob. Agents Chemother. 46:3484–3489.

Downloaded from http://aac.asm.org/ on April 10, 2014 by guest

Linezolid in Children With Cystic Fibrosis. 氯霉素...linezolid in patients with major thermal injuries....ct a1.Pharmacokinetics of Lin ezolid in ...
PHARMACOKINETICS The pharmacokinetics of linezolid ...adults with complicated skin and soft tissue ... linezolid is contraindicated in patients with ...
Linezolid Pharmacokinetics in Adult Patients with Cystic ....unkown
pharmacokinetics of many drugs are altered in patients with cystic fibrosis (CF), often necessitating different dosage requirements than those used in non-...
...of linezolid in adult patients with cystic fibrosis.unkown
January 2004 Serum and sputum concentrations following the oral administration of linezolid in adult patients with cystic fibrosis Dinesh Saralaya1, Daniel G....
...and Oral Linezolid in Adults with Cystic Fibrosis.unkown
Staphylococcus aureus (MRSA) infections in cystic fibrosis (CF) patients. ...Linezolid pharmacokinetics in these adults with CF were well described by a ...
.../tazobactam in adult patients with cystic fibrosis-relat.unkown
10.1093/jac/dkt300 Pharmacokinetics and pharmacodynamics of extended-infusion piperacillin/tazobactam in adult patients with cystic fibrosis-related acute ...
...Pharmacokinetics in Adult Patients with Cystic Fibrosis.unkown
Strathprints Institutional Repository Thomson, Alison (2013) Comparison of NONMEM and pmetrics analysis for aminoglycosides in adult patients with cystic fibrosis...
...Tobramycin in Adult Patients with Cystic Fibrosis.unkown
Adult Cystic Fibrosis Centre,2 and Department of Microbiology,3 Leyenburg ...pharmacokinetics of tobramycin in six patients with cystic fibrosis (CF) ...
...Tazobactam in Adult Patients with Cystic Fibrosis.unkown
1628 Pharmacokinetics and Pharmacodynamics of Extended-Infusion Piperacillin-Tazobactam in Adult Patients with Cystic Fibrosis J.M. BUTTERFIELD,1 T. P. LODIS...
...pharmacokinetics of linezolid in cystic fibrosis patients.unkown
Comparison of elimination and absorption pharmacokinetics of linezolid in cystic fibrosis patients Schaeftlein A.1,2,3, Keel R.4, Kuti J.4, Kloft C.1...
...pharmacokinetics of levofloxacin in adult cystic fibrosis ....unkown
(2006) 153 157 www.elsevier.com/locate/jcf Altered steady state pharmacokinetics of levofloxacin in adult cystic fibrosis patients receiving calcium ...
...of Linezolid in adult patients with cystic fibrosis.unkown
Linezolid in adult patients with cystic fibrosis Article in Journal of Antimicrobial Chemotherapy February 2004 Impact Factor: 5.31 DOI: 10.1093/jac...
Pharmacokinetics of Vancomycin in Adult Cystic Fibrosis ....unkown
To assess vancomycin pharmacokinetics, 10 adult cystic fibrosis patients were given a parenteral dose of vancomycin (15 mg/kg) during the first 72 h of ...
...after Prolonged Treatment of Cystic Fibrosis Patients in ....unkown
Linezolid (LZD)-resistant Staphylococcus aureus (LRSA) isolates were ...LRSA first emerged in 2004 only in cystic fibrosis (CF) patients, ...
...Pharmacokinetics in Patients with Cystic Fibrosis1.unkown
The effect of exocrine pancreatic function on the pharmacokinetics of the ... was evaluated in 10 patients, aged 16-30 yr, with cystic fibrosis. ...
...administered tobramycin in patients with cystic fibrosis.unkown
S66 4. New therapies Posters 69 A randomised comparison of VANTOBRA and TOBI in cystic fibrosis patients with chronic Pseudomonas aeruginosa infection for ...
稳可信 替考拉宁 利奈唑胺的优缺点_图文.ppt
Linezolid in Human Staphylococcal Clinical Isolates ... infection in a patient with cystic fibrosis. ...in adult patients: A consensus review of the ...
Linezolid pharmacokinetics in critically ill patients with ....unkown
//www.icm-experimental.com/content/3/S1/A631 POSTER PRESENTATION Open Access Linezolid pharmacokinetics in critically ill patients with renal replacement ...
Single dose Linezolid Pharmacokinetics in ill Patienys with ....unkown
Single dose Linezolid Pharmacokinetics in ill Patienys with Impaired Renal Function Epecially Chronic Hemodialysis Patients Mona El Assal Associat Professor of ...