Pharmacokinetic Alterations of Antimicrobials in the Critically Ill

Cook, Aaron M.

doi:10.1177/0897190004273568

Cited by 3 publications

(3 citation statements)

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“…Serum concentrations were sequentially obtained 1. 5 (C max ), 3,4,5,8,12, and 24 (trough) hours after the beginning of the intravenous infusion. Serum samples were collected after the first dose only.…”

Section: Methodsmentioning

confidence: 99%

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Pharmacokinetics of Intravenous Levofloxacin Administered at 750 Milligrams in Obese Adults

Cook

Martin

Adams

et al. 2011

Antimicrob Agents Chemother

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The physiochemical properties of levofloxacin suggest that it is an agent which may exhibit altered pharmacokinetics in obese individuals. The purpose of this study was to describe the pharmacokinetics of a single 750-mg intravenous dose of levofloxacin in both hospitalized and ambulatory obese individuals. The hypothesis was that a standard dose of levofloxacin in obese individuals would achieve serum concentrations likely to be therapeutic. A single levofloxacin dose of 750 mg was infused over 90 min, and seven serial serum samples were subsequently obtained to evaluate the pharmacokinetics after the first dose. The peak concentrations of levofloxacin were comparable to those seen with normal-weight individuals. However, the area under the concentration-time curve and clearance were quite variable. Accelerated clearance was evident in the ambulatory obese individuals. Further investigation of the effects of obesity on the pharmacokinetics of levofloxacin is necessary to ensure optimal dosing.

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Section: Methodsmentioning

confidence: 99%

“…Specifically, volume of distribution, hepatic biotransformation, and elimination may be altered (8,14,23). Patients with active inflammatory processes such as burn, trauma, or severe infection have reductions in plasma proteins such as albumin which allow for a higher fraction of unbound drug.…”

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confidence: 99%

Pharmacokinetics of Intravenous Levofloxacin Administered at 750 Milligrams in Obese Adults

Cook

Martin

Adams

et al. 2011

Antimicrob Agents Chemother

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“…Drug pharmacokinetic parameters in ICU patients are often different from those in healthy patients, notably because of physiological alterations induced by sepsis [ 4 - 6 ]. Besides changes in tissue perfusion, protein binding and clearance, the observed alterations in membrane permeability and the subsequently required fluid loading increase the volume of distribution of many drugs, which results in insufficient dosages of some antibiotics in a significant proportion of ICU patients [ 6 - 8 ].…”

Section: Introductionmentioning

confidence: 99%

Effect of fluid loading during hypovolaemic shock on caspofungin pharmacokinetic parameters in pig

et al. 2011

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IntroductionCaspofungin treatment is frequently initiated in shock patients. In the present study, we investigated the influence of hypovolaemic shock requiring fluid loading on the plasma and pulmonary pharmacokinetic parameters of caspofungin in the pig.MethodsAfter being anaesthetised and mechanically ventilated, 12 pigs were bled to induce a two-hour deep shock and resuscitated using normal saline based on haemodynamic goals. A one-hour infusion of 70 mg of caspofungin was started at the beginning of the resuscitation period. The lungs were removed four hours after caspofungin administration. Sixteen animals served as controls without haemorrhage. Caspofungin concentrations were measured by using high-performance liquid chromatography, and a two-compartment population pharmacokinetic analysis was performed.ResultsIn the shock group, the volume of blood removed was 39 ± 7 mL/kg and a volume of 90 ± 17 mL/kg saline was infused throughout the resuscitation period. The extravascular lung water index was higher in the shock group (9.3 ± 1.6 mL/kg vs 5.7 ± 1 mL/kg in the control group; P < 0.01). In the shock group, the median (interquartile range) maximal plasma concentration was 37% lower than in the control group (21.6 μg/mL (20.7 to 22.3) vs 33.1 μg/mL (28.1 to 38.3); P < 0.01). The median area under curve (AUC) from zero to four hours was 25% lower in the shock group than in the control group (60.3 hours × μg/mL (58.4 to 66.4) vs 80.8 hours × μg/mL (78.3 to 96.9); P < 0.01), as was the median lung caspofungin concentration (1.22 μg/g (0.89 to 1.46) vs 1.64 μg/g (1.22 to 2.01); P < 0.01). However, the plasma-to-tissue ratios were not different between the groups, indicating that lung diffusion of caspofungin was not affected after shock followed by fluid loading. Pharmacokinetic analysis showed that the peripheral volume of distribution of caspofungin and intercompartmental clearance were significantly higher in the shock group, as was the total apparent volume of distribution.ConclusionsHypovolaemic shock followed by fluid loading in the pig results in a significant increase in the apparent volume of distribution of caspofungin and in a decrease in its plasma and pulmonary exposition. Although our model was associated with capillary leakage and pulmonary oedema, our results should be generalised to the septic shock with caution. Future investigations should focus on monitoring plasma caspofungin concentrations and optimal caspofungin dosing in shock patients.

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Factors influencing caspofungin plasma concentrations in patients of a surgical intensive care unit

Nguyen

Hoppe-Tichy

Geiss

et al. 2007

Journal of Antimicrobial Chemotherapy

108

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Pharmacokinetic Alterations of Antimicrobials in the Critically Ill

Cited by 3 publications

References 71 publications

Pharmacokinetics of Intravenous Levofloxacin Administered at 750 Milligrams in Obese Adults

Pharmacokinetics of Intravenous Levofloxacin Administered at 750 Milligrams in Obese Adults

Effect of fluid loading during hypovolaemic shock on caspofungin pharmacokinetic parameters in pig

Factors influencing caspofungin plasma concentrations in patients of a surgical intensive care unit

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