Effects of hyperthermia on pharmacokinetics of ertapenem in rats

Boulaméry, Audrey; Marouani, Hafedh; Guilhaumou, Romain; Rocher, Emmanuelle; Simon, Nicolas; Bruguerolle, Bernard

doi:10.1111/j.1472-8206.2008.00586.x

Cited by 4 publications

(4 citation statements)

References 14 publications

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“…In in vitro setting, minimal inhibitory concentrations are decreasing inversely to increasing medium temperatures for numerous antibiotics [ 17 ]. In an animal study performed on rats [ 18 ], an increase in ertapenem concentration was observed in animals exposed to artificial warming. Similarly, increased plasma concentrations of ciprofloxacin were observed in humans who developed a higher fever [ 19 ].…”

Section: Discussionmentioning

confidence: 99%

Better Control of Body Temperature Is Not Associated with Improved Hemodynamic and Respiratory Parameters in Mechanically Ventilated Patients with Sepsis

Markota

Skok

Kalamar

et al. 2022

JCM

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The need for temperature modulation (mostly cooling) in critically ill patients is based on the expected benefits associated with decreased metabolic demands. However, evidence-based guidelines for temperature management in a majority of critically ill patients with fever are still lacking. The aim of our retrospective single-site observational study was to determine the differences in ICU treatment between patients in whom their temperature remained within the target temperature range for ≥25% of time (inTT group) and patients in whom their temperature was outside the target temperature range for <24% of time (outTT group). We enrolled 76 patients undergoing invasive mechanical ventilation for respiratory failure associated with sepsis. We observed no significant differences in survival, mechanical ventilation settings and duration, vasopressor support, renal replacement therapy and other parameters of treatment. Patients in the inTT group were significantly more frequently cooled with the esophageal cooling device, received a significantly lower cumulative dose of acetaminophen and significantly more frequently developed a presence of multidrug-resistant pathogens. In our study, achieving a better temperature control was not associated with any improvement in treatment parameters during ICU stay. A lower prevalence of multidrug-resistant pathogens in patients with higher body temperatures opens a question of a pro-pyrexia approach with an aim to achieve better patient outcomes.

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Section: Discussionmentioning

confidence: 99%

Better Control of Body Temperature Is Not Associated with Improved Hemodynamic and Respiratory Parameters in Mechanically Ventilated Patients with Sepsis

Markota

Skok

Kalamar

et al. 2022

JCM

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“…In our study, results showed no significant modifications of the T 1/2 . According to previous studies, renal drug excretion and metabolism reduction is expected at high core temperature because of a decrease in renal and hepatic blood flow [12,16]. However, as ropivacaine is metabolized by the CYP 1A2 [17] and compared with other enzymatic reactions involving CYP450, it is expected that hyperthermia increases its hepatic metabolic rate.…”

Section: Discussionmentioning

confidence: 99%

Effects of induced hyperthermia on pharmacokinetics of ropivacaine in rats

Guilhaumou¹,

Boulaméry²,

Deluca³

et al. 2010

Fundamemntal Clinical Pharma

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Ropivacaine is a local anaesthetic used for epidural anaesthesia and postoperative pain relief. Hyperthermia is a very common sign of infection associated with variations in physiological parameters, which may influence drugs pharmacokinetics. The aim of this study was to determine the effects of induced hyperthermia on ropivacaine pharmacokinetics in rats. Two groups of six rats were given a single subcutaneous ropivacaine injection. Hyperthermia-induced animals were placed in a water bath to obtain a stable mean core temperature of 39.7 degrees C. After blood samples collection, ropivacaine serum concentrations and pharmacokinetic parameters were determined. Two other groups of six rats were sacrificed 30 min after ropivacaine injection to determine serum and tissues (brain and heart) concentrations. Our results (median +/- inter quartile range) reveal a significant increase of the total apparent clearance (0.0151 +/- 0.000800 L/min vs. 0.0134 +/- 0.00134 L/min), apparent volume of distribution (V(d)) (2.19 +/- 0.27 L vs. 1.57 +/- 0.73 L) and a significant decrease in exposure (488 +/- 50.6 mgxmin/L vs. 572 +/- 110 mgxmin/L) in induced-hyperthermia group. We observed a significant increase in brain ropivacaine concentration in hyperthermic rats (8.39 +/- 8.42 microg/g vs. 3.48 +/- 3.26 microg/g) and no significant difference between cardiac concentrations in the two groups (5.38 +/- 4.83 microg/g vs. 3.73 +/- 2.44 microg/g). Results suggest a higher tissular distribution of ropivacaine and an increase in blood-brain barrier permeability during hyperthermia. The hyperthermia-induced increase in V(d) could be responsible for an increase in cerebral ropivacaine toxicity. These experimental data provide a basis for future clinical investigations in relation to local anaesthetic use in hyperthermic patients.

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“…Also, for some antibiotics increased plasma concentrations were observed in fever range temperatures. In rats, higher plasma concentrations of ertapenem were observed in fever compared to normothermia ( Boulamery et al, 2008 ). Similarly, in humans higher maximum serum concentrations of ciprofloxacin and cefazolin were observed during fever ( Beovic et al, 1999 ).…”

Section: Mechanisms Of Action Of Therapeutic Hyperthermiamentioning

confidence: 99%

Therapeutic hyperthermia for the treatment of infection—a narrative review

et al. 2023

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Modulating body temperature, mostly through the use of antipyretics, is a commonly employed therapeutic intervention in medical practice. However, emerging evidence suggests that hyperthermia could serve as an adjuvant therapy for patients with infection. We performed a narrative review to explore the application of therapeutic hyperthermia in the treatment of infection. A number of studies have been performed in the pre-antibiotic era, enrolling patients with neurosyphilis and gonococcal infections, with reported cure rates at around 60%–80%. We have outlined the potential molecular and immunological mechanisms explaining the possible beneficial effects of therapeutic hyperthermia. For some pathogens increased temperature exerts a direct negative effect on virulence; however, it is presumed that temperature driven activation of the immune system is probably the most important factor affecting microbial viability. Lastly, we performed a review of modern-era studies where modulation of body temperature has been used as a treatment strategy. In trials of therapeutic hypothermia in patients with infection worse outcomes have been observed in the hypothermia group. Use of antipyretics has not been associated with any improvement in clinical outcomes. In modern-era therapeutic hyperthermia achieved by physical warming has been studied in one pilot trial, and better survival was observed in the hyperthermia group. To conclude, currently there is not enough data to support the use of therapeutic hyperthermia outside clinical trials; however, available studies are in favor of at least a temperature tolerance strategy for non-neurocritical patients.

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Effects of hyperthermia on pharmacokinetics of ertapenem in rats

Cited by 4 publications

References 14 publications

Better Control of Body Temperature Is Not Associated with Improved Hemodynamic and Respiratory Parameters in Mechanically Ventilated Patients with Sepsis

Better Control of Body Temperature Is Not Associated with Improved Hemodynamic and Respiratory Parameters in Mechanically Ventilated Patients with Sepsis

Effects of induced hyperthermia on pharmacokinetics of ropivacaine in rats

Therapeutic hyperthermia for the treatment of infection—a narrative review

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