Journal of Antimicrobial Chemotherapy (2000) 45, 329-335
© 2000 The British Society for Antimicrobial Chemotherapy
High vancomycin dosage regimens required by intensive care unit patients cotreated with drugs to improve haemodynamics following cardiac surgical procedures
a Institute of Clinical Pharmacology and Toxicology, DPMSC, University of Udine, P. le S. Maria della Misericordia 3, 33100 Udine; b Division of Cardiothoracic Surgery, S. M. Misericordia Udine Hospital, Udine, Italy
 |
Abstract |
|---|
 Top Abstract IntroductionPatients and methodsResultsDiscussionReferences |
|---|
The aim of this study was to evaluate retrospectively the importance of a Bayesian pharmacokinetic approach for predicting vancomycin concentrations to individualize its dosing regimen in 18 critically ill patients admitted to intensive care units following cardiothoracic surgery. The possible influence of some coadministered drugs with important haemodynamic effects (dopamine, dobutamine, frusemide) on vancomycin pharmacokinetics was assessed. Vancomycin serum concentrations were measured by fluorescence polarization immunoassay. Vancomycin dosage regimens predicted by the Bayesian method (Da) were compared retrospectively with Moellering's nomogram-based dosages (DM) to assess possible major differences in vancomycin dosing. Da values were similar to DM in 10 patients (Da
DM group) (20.52 ± 8.40 mg/kg/day versus 18.81 ± 7.24 mg/kg; P = 0.15), whereas much higher dosages were required in the other eight patients (Da >> DM group) (26.78 ± 3.01 mg/kg/day versus 18.95 ± 3.41 mg/kg/day; P < 0.0001) despite no major difference in attained vancomycin steady-state trough concentration (Cmin ss) (9.22 ± 1.33 mg/L versus 8.99 ± 1.26 mg/L; = 0.75) or estimated creatinine clearance (1.23 ± 0.49 mL/min/kg versus 1.21 ± 0.24 mL/min/kg; P = 0.95) being found between the two groups. The ratio between Da and DM was significantly higher in the Da >> DM group than in the Da DM group (1.44 ± 0.18 versus 1.10 ± 0.21; P < 0.01). In four Da >> DM patients the withdrawal of cotreatment with haemodynamically active drugs was followed by a sudden substantial increase in the vancomycin Cmin ss (13.30 ± 1.13 mg/L versus 8.79 ± 0.87 mg/L; P < 0.01), despite no major change in bodyweight or estimated creatinine clearance being observed. We postulate that these drugs with important haemodynamic effects may enhance vancomycin clearance by inducing an improvement in cardiac output and/or renal blood flow, and/or by interacting with the renal anion transport system, and thus by causing an increased glomerular filtration rate and renal tubular secretion. Given the wide simultaneous use of vancomycin and dopamine and/or dobutamine and/or frusemide in patients admitted to intensive care units, clinicians must be aware of possible subtherapeutic serum vancomycin concentrations when these drugs are coadministered. Therefore, therapeutic drug monitoring (TDM) for the pharmacokinetic optimization of vancomycin therapy is strongly recommended in these situations. |
Introduction |
|---|
|
TopAbstractIntroductionPatients and methodsResultsDiscussionReferences |
|---|
Vancomycin is one of the most potent agents against life-threatening Gram-positive bacterial infections affecting patients hospitalized in intensive care units, especially when multi-resistant bacterial isolates are involved.1 Standard doses suggested by the manufacturer and dosing nomograms represent the two most common methods for initiating vancomycin dosing regimens. Several investigators have developed various dosing nomograms,2–6 most of which use a fixed vancomycin distribution volume and consider creatinine clearance as the most accurate predictor of vancomycin clearance. However, as inter- and intrapatient variability in vancomycin disposition have been found to be wide,7,8 an individualized approach to vancomycin dosing regimens through the use of measured serum concentrations to avoid vancomycin-related nephro- and ototoxicity9,10 and to improve efficacy has been strongly advocated.10,11 This practice of therapeutic drug monitoring (TDM) is considered mandatory in the management of vancomycin therapy when certain pathophysiological conditions (e.g. impairment of renal function, burns, iv drug abuse)12 or other risk factors (e.g. coadministration of cyclosporin, aminoglycosides, amphotericin B)13 coexist. Therapeutic peak (20–40 mg/L) and trough (5–10 mg/L) serum ranges have been identified and are accepted worldwide.14,15 Recently, the design of individualized dosage regimens for vancomycin has been improved by means of Bayesian principles.16–18 These methods have been validated in various pathophysiological conditions, such as critically ill patients with haematological malignancies and in intensive care units, and appear to be suitable for routine clinical practice.19,20 On these bases, we wanted to evaluate retrospectively a Bayesian pharmacokinetic approach for predicting vancomycin concentrations to individualize its dosing regimen in critically ill patients admitted to an intensive care unit following cardiothoracic surgery, this being a population with possible unstable cardiac output and rapidly changing renal function. More relevantly, the coadministration of some drugs with substantial haemodynamic effects, such as dopamine, dobutamine and frusemide, may commonly be required for temporary inotropic support and to preserve renal function after cardiac surgical procedures. Therefore, the main purpose of our study was to assess the possible influence of these haemodynamically active coadministered drugs on vancomycin pharmacokinetics.
|
Patients and methods |
|---|
|
TopAbstractIntroductionPatients and methodsResultsDiscussionReferences |
|---|
We evaluated retrospectively data collected from 18 (ten male, eight female) critically ill patients (Table I
) admitted to intensive care units following cardiac surgical procedures at the Cardiothoracic Surgery Department of the S. M. Misericordia Udine Hospital over a 1 year period. All the eligible patients received vancomycin to treat documented acute infections caused by staphylococci (Staphylococcus aureus and coagulase-negative staphylococci) and were cotreated with at least one drug with important haemodynamic effects: six with dopamine plus dobutamine plus frusemide; six with dobutamine plus frusemide; one with dopamine plus frusemide; and five with frusemide alone. All these drugs were administered by continuous iv infusion. Creatinine clearance (ClCr) was estimated by means of the Cockcroft & Gault formula.21 TDM of vancomycin was performed after at least 48 h of therapy and then repeated every 1–5 days throughout the treatment period. Blood samples were collected a few minutes before the next drug administration to determine the trough serum concentration (Cmin ss) and 30 min after the end of a 1 h intermittent vancomycin infusion to determine the peak serum concentration (Cmax ss). After centrifugation, serum samples were analysed within 2 h by means of a fluorescence polarization immunoassay (TDx, Abbott Laboratories, Abbott Park, IL, USA). The interday and intraday coefficient of variation of the assay was <10%. As all the patients had normal renal function (serum creatinine < 1.5 mg/dL), no overestimation of vancomycin concentration as a result of antibiotically inactive vancomycin crystalline degradation product (CDP-1) was expected.22 Each patient's characteristics together with his or her individual vancomycin dosage regimen and TDM results were analysed by means of a pharmacokinetic computer program (PKS, Abbott Pharmacokinetic System, Abbott Laboratories)23 based on the Bayesian approach, to predict what would have been the best individualized vancomycin dosing regimen to reach the therapeutic peak and trough serum ranges. Indeed, as vancomycin exhibits time-dependent bactericidal activity,24–26 the time during which free serum concentration persists above the MIC for the pathogen involved should be considered the major pharmacokinetic–pharmacodynamic factor determining its in vivo bactericidal activity.27,28 Therefore, as some bacterial isolates may show intermediate sensitivity (MIC 2–4 mg/L) and vancomycin is about 50% serum protein bound,29 our pharmacokinetic approach was focused on attaining a vancomycin steady-state serum trough concentration as close as possible to the upper limit of the therapeutic range (10 mg/L), to maximize efficacy while minimizing potential toxicological risks. The total daily dosage was in 2–4 intermittent 1 h iv infusions, the amount of each single dose being 500 mg or less. Vancomycin administered dosage regimens predicted by the Bayesian method (Da) were then compared retrospectively with Moellering's nomogram-based dosages (DM)5 to assess possible major differences in vancomycin dosing and to evaluate to what extent the estimated creatinine clearance as predictor of vancomycin clearance in such a population could be considered accurate. In agreement with other workers' findings,30 instead of lean bodyweight, actual bodyweight was taken into account to estimate vancomycin daily dosage per kg, although none of the patients was morbidly obese (range of actual bodyweight between 38.2 and 90.5 kg). Furthermore, on the basis of the difference observed between Da and DM, the 18 patients involved in this study were subsequently divided into two groups: the first group (Da DM group; n = 10) included patients requiring a Da similar to DM (Da/DM ratio < 1.20 during most of the cotreatment period); the second group (Da >> DM group; n = 8) included patients requiring a Da much larger than DM (Da/DM ratio > 1.20 during most of the cotreatment period).
|
Statistical evaluations were performed using Student's t test for paired or unpaired data as appropriate by means of SigmaStat 2.0 (SPSS, Science Software GmbH, Erkrath, Germany).
Data were expressed as mean ± standard deviation (S.D.) and 95% confidence intervals for difference of mean values (CI) were calculated.
|
Results |
|---|
|
TopAbstractIntroductionPatients and methodsResultsDiscussionReferences |
|---|
The mean (± S.D.) Bayesian predicted administered dosage regimens of vancomycin (Da) required to attain the desired peak (21.69 ± 4.95 mg/L) and steady upper limit serum trough concentration (9.12 ± 1.26 mg/L) (Cmin ss) were significantly higher than those suggested by Moellering's nomogram (DM) during cotreatment with haemodynamically active drugs when considering the group of patients as a whole (23.30 ± 7.16 mg/kg/day versus 18.87 ± 5.70 mg/kg/24 h; P < 0.001; CI 2.31–6.56). However, we observed that Da values were similar to DM in 10 patients (Da
DM group) (20.52 ± 8.40 mg/kg/day versus 18.81 ± 7.24 mg/kg/day; P = 0.15; CI –0.73 to 4.16) (Figure 1), whereas much higher dosages were required in the other eight patients (Da >> DM group) (26.78 ± 3.01 mg/kg/day versus 18.95 ± 3.41 mg/kg/day; P < 0.0001; CI 5.84–9.83) (Figure 2), despite no major difference in attained vancomycin Cmin ss (9.22 ± 1.33 mg/L versus 8.99 ± 1.26 mg/L; P = 0.75; CI –1.50 to 1.10) or estimated ClCr (1.23 ± 0.49 mL/min/kg versus 1.21 ± 0.24 mL/min/kg; P = 0.95; CI –0.41 to 0.39) being found between the former group and the latter group. The relationship between the administered dosages of vancomycin, the Moellering's nomogram- based dosages, the estimated ClCr and the trough concentrations reached during the whole TDM observation period in the Da >> DM group are shown in Table II. Of the patients requiring a Da much larger than DM, four (patients V–VIII) had the haemodynamically active drugs suspended owing to clinical improvement before the discontinuation of the vancomycin treatment. It is worth noting that the withdrawal of these cotreatments was followed by a sudden substantial increase in the vancomycin Cmin ss (13.30 ± 1.13 mg/L versus 8.79 ± 0.87 mg/L; P < 0.01; CI 2.51–7.79), despite the fact that no major changes in bodyweight or estimated creatinine clearance were observed. Therefore, significant vancomycin dosage reductions were required (4.26 ± 1.51 mg/kg/24 h) to avoid exaggerated vancomycin total body exposure and to lower vancomycin trough concentration as close as possible to the desired therapeutic range (10.84 ± 1.51 mg/L) (Figure 2).
|
, P1 (DBT + DPM + FSM); 
, P2 (DBT + DPM + FSM); 
, P3 (DBT + FSM); 
, P4 (FSM); 
, P5 (DBT + FSM); 
, P6 (FSM); 
, P7 (FSM); 
, P8 (FSM); 
, P9 (FSM); •, P10 (DBT + FSM).
|
, PV (stop);
|
|
Discussion |
|---|
|
TopAbstractIntroductionPatients and methodsResultsDiscussionReferences |
|---|
The findings suggest a major role played by coadministered drugs with important haemodynamic effects on vancomycin pharmacokinetics in intensive care unit patients admitted following cardiac surgery. The well-known wide intra- and inter-individual pharmacokinetic variability of vancomycin might account only partially for the high vancomycin dosages per kg required during the period of cotreatment in these patients. In fact, whereas the average differences between Da and DM were moderate (<20%) in ten patients (Da
DM group), they were much higher (21–90%) in the other eight patients (Da >> DM group), despite the fact that no major differences in attained Cmin ss or estimated ClCr were found between the two groups. Moreover, as no patients had major fluid overload, the high vancomycin dosages required seem unlikely to be due to an increased volume of distribution. Therefore, we postulate that drugs with important haemodynamic effects may enhance vancomycin clearance by inducing an improvement in cardiac output and/or renal blood flow. The significant vancomycin dosage reductions required by four Da >> DM patients to avoid an exaggerated vancomycin total body exposure and to lower trough concentration within the therapeutic range the day after the withdrawal of the haemodynamically active drugs is in agreement with this hypothesis. As far as the possible mechanism of this enhanced clearance is concerned, it has to be taken into account that Moellering's nomogram is based on ClCr and the latter is considered to be a surrogate marker of glomerular filtration rate. Therefore, the wide differences between Da and DM observed in the Da >> DM group suggest that the enhanced vancomycin clearance may be induced not only by an increased glomerular filtration rate, but also by a significant augmentation of its renal tubular secretion, considering that nonrenal routes account only slightly for vancomycin clearance. The observation that no major changes in serum creatinine or estimated ClCr occurred in those four Da >> DM patients continuing vancomycin treatment after the withdrawal of the haemodynamically active drugs further strengthens this hypothesis. Indeed, as the observations of Rodvold et al.,6 Rybak et al.29 and Golper et al.31 indicate that tubular secretion may be considered a significant component of vancomycin's net renal excretion, an increase of renal blood flow and/or an interaction with the renal anion transport system induced by these coadministered drugs may explain our findings.
Many investigators have previously documented that dopamine, dobutamine and frusemide may exert direct or indirect substantial haemodynamic effects on renal blood flow.
Dopamine may increase cardiac output through stimulation of adrenergic receptors and shows important vasodilating effects at the renal level in a dose-dependent fashion, mainly secondary to a stimulation of renal vascular dopaminergic D1 receptors.32,33
No definitive relationship between dobutamine and haemodynamic effect on renal blood flow has been demonstrated. Conflicting opinions have been expressed, with some papers suggesting that dobutamine may enhance renal blood flow secondary to increases in cardiac contractility and cardiac output and perhaps to an arterial vasodilating effect both in humans and in animals.34,35
Several investigators documented that glomerular filtration rate and renal blood flow significantly increased after frusemide administration both in animals and in humans, probably by releasing prostaglandin E2.36–39 Furthermore, Nivoche et al.40 showed that in rabbits the administration of frusemide enhanced vancomycin tubular secretion without any effect on the filtered load.
Accordingly, all of these haemodynamically active drugs (dopamine, dobutamine, frusemide) may enhance renal blood flow and theoretically vancomycin renal clearance. Indeed, it should be noted that this effect did not have the same importance in all subjects, but was mainly seen in patients receiving simultaneously at least two of these drugs by iv continuous infusion (dobutamine plus frusemide in four cases and dopamine plus dobutamine plus frusemide in another four cases). These findings could be explained by a synergic effect between dopamine and/or dobutamine and/or frusemide, on renal blood flow. Moreover, the degree of their induced effect on vancomycin renal clearance may be extremely variable, seeing that it was higher in some patients. Indeed, our patients were given different doses of these haemodynamically active drugs from day to day according to clinical status. Because of this, no definitive relationship between the haemodynamic effect and the administered dose could be found.
In conclusion, our findings show a wide vancomycin inter-individual pharmacokinetic variability in intensive care unit patients cotreated with drugs to improve haemodynamics following cardiac surgical procedures, and suggest that the estimated ClCr should not always be considered as an accurate predictor of vancomycin clearance. In fact, some cotreated patients required much higher vancomycin dosages than those estimated on the basis of the creatinine clearance only. Given the wide simultaneous use of vancomycin and dopamine and/or dobutamine and/or frusemide in patients admitted to intensive care units, clinicians must be aware of possible subtherapeutic serum vancomycin concentrations when these drugs are coadministered. Therefore, TDM for the pharmacokinetic optimization of vancomycin therapy is strongly recommended in these situations. On these bases, we are going to begin a prospective study to evaluate this potential interaction.
|
Notes |
|---|
* Corresponding author. Tel/Fax: +39-432-559833; E-mail: federico.pea{at}med.uniud.it
|
References |
|---|
|
TopAbstractIntroductionPatients and methodsResultsDiscussionReferences |
|---|
1 . Wilhelm, M. P. (1991). Vancomycin. Mayo Clinic Proceedings 66, 1165–70.[Web of Science][Medline]
2 . Brown, D. L. & Mauro, L. S. (1988). Vancomycin dosing chart for use in patients with renal impairment. American Journal of Kidney Diseases 11, 15–19.[Web of Science][Medline]
3 . Lake, K. D. & Peterson, C. D. (1985). A simplified dosing method for initiating vancomycin therapy. Pharmacotherapy 5, 340–4.[Web of Science][Medline]
4
.
Matzke, G. R., McGory, R. W., Halstenson, C. E. & Keane, W. F. (1984). Pharmacokinetics of vancomycin in patients with various degrees of renal function. Antimicrobial Agents and Chemotherapy 25, 433–7.
5 . Moellering, R. C., Jr, Krogstad, D. J. & Greenblatt, D. J. (1981). Vancomycin therapy in patients with impaired renal function: a nomogram for dosage. Annals of Internal Medicine 94, 343–6.
6
.
Rodvold, K. A., Blum, R. A., Fischer, J. H., Zokufa, H. Z., Rotschafer, J. C., Crossley, K. B. et al. (1988). Vancomycin pharmacokinetics in patients with various degrees of renal function. Antimicrobial Agents and Chemotherapy 32, 848–52.
7
.
Healy, D. P., Polk, R. E., Garson, M. L., Rock, D. T. & Comstock, T. J. (1987). Comparison of steady-state pharmacokinetics of two dosage regimens of vancomycin in normal volunteers. Antimicrobial Agents and Chemotherapy 31, 393–7.
8 . Moellering, R. C., Jr (1984). Pharmacokinetics of vancomycin. Journal of Antimicrobial Chemotherapy 14, Suppl. D, 43–52.
9 . Chow, A. W. & Azar, R. M. (1994). Glycopeptides and nephrotoxicity. Intensive Care Medicine 20, Suppl. 4, S23–9.
10 . Welty, T. E. & Copa, A. K. (1994). Impact of vancomycin therapeutic drug monitoring on patient care. Annals of Pharmacotherapy 28, 1335–9.[Abstract]
11 . Marra, F., Cairns, B. & Jewesson, P. (1996). Vancomycin serum concentration monitoring. The middle ground is best. Clinical Drug Investigation 12, 105–18.
12 . Leader, W. G., Chandler, M. H. H. & Castiglia, M. (1995). Pharmacokinetic optimisation of vancomycin therapy. Clinical Pharmacokinetics 28, 327–42.[Web of Science][Medline]
13 . Pauly, D. J., Musa, D. M., Lestico, M. R., Lindstorm, M. J. & Hetsko, C. M. (1990). Risk of nephrotoxicity with combination vancomycin–aminoglycoside antibiotic therapy. Pharmacotherapy 10, 378–82.[Web of Science][Medline]
14
.
Rybak, M. J., Albrecht, L. M., Boike, S. C. & Chandrasekar, P. H. (1990). Nephrotoxicity of vancomycin, alone and with an aminoglycoside. Journal of Antimicrobial Chemotherapy 25, 679–87.
15 . Fernandez de Gatta, M. D., Calvo, M. V., Hernandez, J. M., Caballero, D., San Miguel, J. F. & Dominguez-Gil, A. (1996). Cost-effectiveness analysis of serum vancomycin concentration monitoring in patients with hematologic malignancies. Clinical Pharmacology and Therapeutics 60, 332–40.[Web of Science][Medline]
16 . Burton, M. E., Gentle, D. L. & Vasko, M. R. (1989). Evaluation of Bayesian method for predicting vancomycin dosing. Drug Intelligence and Clinical Pharmacy 23, 294–300.
17 . Rodvold, K. A., Pryka, R. D., Garrison, M. & Rotschafer, J. C. (1989). Evaluation of a two-compartment Bayesian forecasting program for predicting vancomycin concentrations. Therapeutic Drug Monitoring 11, 269–75.[Web of Science][Medline]
18
.
Hurst, A. K., Yoshinaga, M. A., Mitani, G. H., Foo, K. A., Jeliffe, R. W. & Harrison, E. C. (1990). Application of a Bayesian method to monitor and adjust vancomycin dosage regimens. Antimicrobial Agents and Chemotherapy 34, 1165–71.
19 . Fernadez de Gatta, M. M., Fruns, I. & Dominguez-Gil, A. (1994). Individualizing vancomycin dosing regimens: an evaluation of two pharmacokinetic dosing programs in critically ill patients. Pharmacotherapy 14, 196–201.[Web of Science][Medline]
20 . Furlanut, M., Pea, F., Baraldo, M., Nardi, G., Di Silvestre, A., Bertolissi, M. et al. (1997). The importance of a bayesian pharmacokinetic approach in improving vancomycin therapeutic use. European Journal of Clinical Pharmacology 52, Suppl., Second Congress of the European Association for Clinical Pharmacology and Therapeutics (EACPT), Berlin, Germany, 17–20 September 1997. Abstract 500, p. A158.
21 . Cockroft, D. W. & Gault, M. H. (1976). Prediction of creatinine clearance from serum creatinine. Nephron 16, 31–41.[Web of Science][Medline]
22 . Anne, L., Hu, M., Chan, K., Colin, L. & Gottwald, K. (1989). Potential problem with fluorescence polarization immunoassay cross-reactivity to vancomycin degradation product CDP-1: its detection in sera of renally impaired patients. Therapeutic Drug Monitoring 11, 585–91.[Web of Science][Medline]
23 . Poirier, T. I. & Gindici, R. A. (1992). Survey of clinical pharmacokinetic software for microcomputers. Hospital Pharmacy 27, 971–7.[Medline]
24 . Craig, W. (1993). Pharmacodynamics of antimicrobial agents as a basis for determining dosage regimens. European Journal of Microbiology and Infectious Diseases 12, Suppl. 1, S6–8.
25
.
Ackerman, B. H., Vannier, A. M. & Eudy, E. B. (1992). Analysis of vancomycin time–kill studies with Staphylococcus species by using a curve stripping program to describe the relationship between concentration and pharmacodynamic response. Antimicrobial Agents and Chemotherapy 36, 1766–9.
26
.
Larsson, A. J., Walker, K. J., Raddatz, J. K. & Rotschafer, J. C. (1996). The concentration-independent effect of monoexponential and biexponential decay in vancomycin concentrations on the killing of Staphylococcus aureus under aerobic and anaerobic condition. Journal of Antimicrobial Chemotherapy 38, 589–97.
27 . Rotschafer, J. C., Zabinski, R. A. & Walker, K. J. (1992). Pharmacodynamic factors of antibiotic efficacy. Pharmacotherapy 12, Suppl., S64–70.
28 . MacGowan, A. P. (1998). Pharmacodynamics, pharmacokinetics, and therapeutic drug monitoring of glycopeptides. Therapeutic Drug Monitoring 20, 473–7.[Web of Science][Medline]
29
.
Rybak, M. J., Albrecht, L. M., Berman, J. R., Warbasse, L. H. & Svensson, C. K. (1990). Vancomycin pharmacokinetics in burn patients and intravenous drug abusers. Antimicrobial Agents and Chemotherapy 34, 792–5.
30 . Bauer, L. A., Black, D. J. & Lill, J. S. (1998). Vancomycin dosing in morbidly obese patients. European Journal of Clinical Pharmacology 54, 621–5.[Web of Science][Medline]
31 . Golper, T. A., Noonan, H. M., Elzinga, L., Gilbert, D., Brummett, R., Anderson, J. L. et al. (1988). Vancomycin pharmacokinetics, renal handling, and non renal clearances in normal human subjects. Clinical Pharmacology and Therapeutics 43, 565–70.[Web of Science][Medline]
32 . Olsen, N. V. (1998). Effects of dopamine on renal haemodynamics tubular function and sodium excretion in normal humans. Danish Medical Bulletin 45, 282–97.[Web of Science][Medline]
33 . Mousdale, S., Clyburn, P. A., Mackie, A. M., Groves, N. D. & Rosen, M. (1988). Comparison of the effects of dopamine, dobutamine, and dopexamine upon renal blood flow: a study in normal health volunteers. British Journal of Clinical Pharmacology 25, 555–60.[Web of Science][Medline]
34
.
Leier, C. V., Webel, J. & Bush, C. A. (1977). The cardiovascular effects of the continuous infusion of dobutamine in patients with severe cardiac failure. Circulation 56, 468–72.
35
.
Lass, N. A., Glock, D. & Goldberg, L. I. (1988). Cardiovascular and renal hemodynamic effects of intravenous infusions of the selective DA1 agonist, fenoldopam, used alone or in combination with dopamine and dobutamine. Circulation 78, 1310–15.
36
.
Ludens, J. H., Hook, J. B., Brody, M. J. & Williamson, H. E. (1968). Enhancement of renal blood flow by furosemide. Journal of Pharmacology and Experimental Therapeutics 163, 456–60.
37 . Williamson, H. E., Bourland, W. A., Marchand, G. R., Farley, D. B. & Van Orden, D. E. (1975). Furosemide induced release of prostaglandin E to increase renal blood flow. Proceedings of the Society for Experimental Biology and Medicine 150, 104–6.[Medline]
38 . Nuutinen, L. S. & Tuononen, S. (1976). The effect of furosemide on renal blood flow and renal tissue oxygen tension in dogs. Annales Chirurgiae et Gynaecologiae 65, 272–6.[Web of Science][Medline]
39 . Ljubicic, N., Bilic, A. & Plavsic, V. (1992). Effect of propranolol on urinary prostaglandin E2 excretion and renal interlobar arterial blood flow after furosemide administration in patients with hepatic cirrhosis. European Journal of Clinical Pharmacology 43, 555–8.[Web of Science][Medline]
40
.
Nivoche, Y., Contrepois, A., Cremieux, A. C. & Carbon, C. (1982). Vancomycin in rabbits: pharmacokinetics, extravascular diffusion, renal excretion, and interactions with furosemide. Journal of Pharmacology and Experimental Therapeutics 222, 237–40.
Received 20 May 1999; returned 10 August 1999; revised 3 September 1999; accepted 2 November 1999
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  A. H. Thomson, C. E. Staatz, C. M. Tobin, M. Gall, and A. M. Lovering Development and evaluation of vancomycin dosage guidelines designed to achieve new target concentrations J. Antimicrob. Chemother., May 1, 2009; 63(5): 1050 - 1057. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. H. Nguyen, T. Hoppe-Tichy, H. K. Geiss, A. C. Rastall, S. Swoboda, J. Schmidt, and M. A. Weigand Factors influencing caspofungin plasma concentrations in patients of a surgical intensive care unit J. Antimicrob. Chemother., July 1, 2007; 60(1): 100 - 106. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. S. Buelga, M. del Mar Fernandez de Gatta, E. V. Herrera, A. Dominguez-Gil, and M. J. Garcia Population Pharmacokinetic Analysis of Vancomycin in Patients with Hematological Malignancies Antimicrob. Agents Chemother., December 1, 2005; 49(12): 4934 - 4941. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Lipman, S. C. Wallis, and R. J. Boots Cefepime Versus Cefpirome: The Importance of Creatinine Clearance Anesth. Analg., October 1, 2003; 97(4): 1149 - 1154. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Pea, L. Brollo, P. Viale, F. Pavan, and M. Furlanut Teicoplanin therapeutic drug monitoring in critically ill patients: a retrospective study emphasizing the importance of a loading dose J. Antimicrob. Chemother., April 1, 2003; 51(4): 971 - 975. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||