A novel way to investigate the effects of plasma exchange on antibiotic levels: use of microdialysis

Roberts, Jason A.; Roberts, Michael S.; Robertson, Thomas A.; Cross, Sheree E.; Lipman, Jeffrey

doi:10.1016/j.ijantimicag.2007.09.013

Cited by 16 publications

(6 citation statements)

References 20 publications

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“…Our study provides several insights regarding the PK and dosage requirements of amoxicillin in this population with known distinct PK characteristics. The PK of burn patients is indeed altered due to different phenomena, such as capillary leak syndrome, mechanical ventilation, hypoalbuminemia, extracorporeal circuits, and postchirurgical drains; in addition, significant burn injuries themselves might increase the volume of distribution of hydrophilic drugs (26)(27)(28)(29)(30)(31).…”

Section: Discussionmentioning

confidence: 99%

Population Pharmacokinetic Study of Amoxicillin-Treated Burn Patients Hospitalized at a Swiss Tertiary-Care Center

Fournier

Goutelle

Que

et al. 2018

Antimicrob Agents Chemother

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The objective of this study was to investigate the population pharmacokinetics (PK) of amoxicillin in ICU burn patients and the optimal dosage regimens. This was a prospective study involving 21 consecutive burn patients receiving amoxicillin. PK data were analyzed using nonlinear mixed-effects modeling. Monte-Carlo simulations assessed the influence of various amoxicillin dosage regimens with identified covariates on the probability to achieve a target (PTA) value of time during which free amoxicillin concentrations in plasma exceeded the MIC (T>MIC). A two-compartment model best described the data. Creatinine clearance (CL) and body weight (BW) influenced amoxicillin CL and central volume of distribution (), respectively. The median CL (Cockcroft-Gault formula) was high (128 ml/min), with 25% of patients having CLs of >150 ml/min. The CL, , and half-life () values at steady state for a patient with a CL of 110 ml/min and BW of 70 kg were 13.6 liters/h, 9.7 liters, and 0.8 h, respectively. Simulations showed that a target T>MIC of ≥50% was achieved (PTA > 90%) with standard amoxicillin dosage regimens (1 to 2 g every 6 to 8 h [q6-8h]) when the MIC was low (<1 mg/liter). However, increased dosages of up to 2 g/4 h were necessary in patients with augmented CLs or higher MICs. Prolonging amoxicillin infusion from 30 min to 2 h had a favorable effect on target attainment. In conclusion, this population analysis shows an increased amoxicillin CL and substantial CL PK variability in burn patients compared to literature data with nonburn patients. Situations of augmented CL and/or high bacterial MIC target values may require dosage increases and longer infusion durations. (This study has been registered at ClinicalTrials.gov under identifier NCT01965340.).

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Section: Discussionmentioning

confidence: 99%

Population Pharmacokinetic Study of Amoxicillin-Treated Burn Patients Hospitalized at a Swiss Tertiary-Care Center

Fournier

Goutelle

Que

et al. 2018

Antimicrob Agents Chemother

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“…In vivo evaluations using cutaneous microdialysis have been used for quantification of cerebral neurotransmitters (Shearman et al, 2006;Cerbai et al, 2007;Shannon et al, 2013), glucose monitoring in diabetes mellitus (Mader et al, 2012), measurement of antibiotics levels (Roberts et al, 2008;K. Hurtado et al, 2014), and measurement of antineoplastic drug levels in the target tissue (Höcht, Opezzo, Taira, 2007).…”

Section: Cutaneous Microdialysismentioning

confidence: 99%

Evaluation of skin absorption of drugs from topical and transdermal formulations

Ruela

Perissinato

Lino

et al. 2016

Braz. J. Pharm. Sci.

217

135

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The skin barrier function has been attributed to the stratum corneum and represents a major challenge in clinical practice pertaining to cutaneous administration of drugs. Despite this, a large number of bioactive compounds have been successfully administered via cutaneous administration because of advances in the design of topical and transdermal formulations. In vitro and in vivo evaluations of these novel drug delivery systems are necessary to characterize their quality and efficacy. This review covers the most well-known methods for assessing the cutaneous absorption of drugs as an auxiliary tool for pharmaceutical formulation scientists in the design of drug delivery systems. In vitro methods as skin permeation assays using Franz-type diffusion cells, cutaneous retention and tape-stripping methods to study the cutaneous penetration of drugs, and in vivo evaluations as pre-clinical pharmacokinetic studies in animal models are discussed. Alternative approaches to cutaneous microdialysis are also covered. Recent advances in research on skin absorption of drugs and the effect of skin absorption enhancers, as investigated using confocal laser scanning microscopy, Raman confocal microscopy, and attenuated total reflectance Fourier-transform infrared spectroscopy, are reviewed. Uniterms:Skin absorption/effects/study. Skin absorption/topical formulations. Skin absorption/ transdermal formulations. Skin absorptions/enhancers. INTRODUCTIONTopical and transdermal drug delivery systems have shown significant advantages in clinical practice for drug targeting to the action site in the body; this has reduced the systemic side effects. The administration of drugs by through the skin is also performed to achieve controlled or prolonged drug delivery, and this route can be explored as an alternative to the oral route. The oral route shows some limitations for drugs with irregular absorption in the gastrointestinal tract and low bioavailability and for drugs with increased first pass metabolism and short plasma halflife times (Barry, 2001;Wokovich et al., 2006;Prausnitz, Langer, 2009;Alexander et al., 2012).Many drug products applied to the skin surface may penetrate to some extent into the skin layers, where their effects are expected. This is the case for topical formulations for treatment of skin disorders such as acne and cutaneous inflammatory diseases that include dermatitis, erythematous lupus, and psoriasis. On the other hand, transdermal formulations release drugs that permeate through the skin and enter the systemic circulation. Transdermal therapy must ensure that significant concentrations of the drug are absorbed to reach effective plasma concentrations. Permeation of drugs is targeted in some cases to body regions close to the action site, where a regional effect is expected, e.g., in the muscles, blood vessels, and articulations. In this way, the term "cutaneous absorption" is properly used to characterize the sum of the amounts of drug that penetrate and permeate the skin (Barry, 2001;El Maghraby, Barry;Willi...

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“…Monitoring drug concentrations should be considered not only in blood, but also other biological fluids that may more likely represent the target site of activity (e.g peritoneal fluid, epithelial lining fluid, cerebrospinal fluid. An alternative, albeit far more costly approach to measuring drug concentrations in tissues, is microdialysis, an in vivo sampling technique that can also facilitate drug concentration measurement in peripheral tissues such as muscle and subcutaneous adipose tissue, as well as various other tissues including the heart and lung [21,22].…”

Section: Accepted Manuscriptmentioning

confidence: 99%

Understanding the impact of pathophysiological alterations during critical illness on drug pharmacokinetics

Jamal

Roger

Roberts

2018

Anaesthesia Critical Care & Pain Medicine

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A novel way to investigate the effects of plasma exchange on antibiotic levels: use of microdialysis

Cited by 16 publications

References 20 publications

Population Pharmacokinetic Study of Amoxicillin-Treated Burn Patients Hospitalized at a Swiss Tertiary-Care Center

Population Pharmacokinetic Study of Amoxicillin-Treated Burn Patients Hospitalized at a Swiss Tertiary-Care Center

Evaluation of skin absorption of drugs from topical and transdermal formulations

Understanding the impact of pathophysiological alterations during critical illness on drug pharmacokinetics

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