Tissue pharmacokinetics of ertapenem at steady-state in diabetic patients with leg infections

Sauermann, Robert; Burian, Bernhard; Burian, Angela; Jäger, Walter; Höferl, Martina; Stella, Alexander; Theurer, Stefanie; Riedl, Michaela; Zeitlinger, Markus

doi:10.1093/jac/dks479

Cited by 17 publications

(10 citation statements)

References 27 publications

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“…The mean volume of distribution calculated by KinFIT was lower for MDR-TB patients than for the healthy volunteers, whereas the mean clearance was higher for the MDR-TB patients than for the healthy volunteers. Our observations are consistent with other studies that showed a lower drug exposure of ertapenem in patients with infectious diseases [23][24][25]. More surprising was the intervariability in AUC between patients with MDR-TB.…”

Section: Discussionsupporting

confidence: 93%

Pharmacokinetics of ertapenem in patients with multidrug-resistant tuberculosis

et al. 2016

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Treatment of multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis (TB) is becoming more challenging because of increased levels of drug resistance against second-line TB drugs. One promising group of antimicrobial drugs is carbapenems. Ertapenem is an attractive carbapenem for the treatment of MDR- and XDR-TB because its relatively long half-life enables once-daily dosing.A retrospective study was performed for all patients with suspected MDR-TB at the Tuberculosis Center Beatrixoord of the University Medical Center Groningen (Haren, the Netherlands) who received ertapenem as part of their treatment regimen between December 1, 2010 and March 1, 2013. Safety and pharmacokinetics were evaluated.18 patients were treated with 1000 mg ertapenem for a mean (range) of 77 (5-210) days. Sputum smear and culture were converted in all patients. Drug exposure was evaluated in 12 patients. The mean (range) area under the concentration-time curve up to 24 h was 544.9 (309-1130) h·mg·L(-1) The mean (range) maximum observed plasma concentration was 127.5 (73.9-277.9) mg·L(-1)In general, ertapenem treatment was well tolerated during MDR-TB treatment and showed a favourable pharmacokinetic/pharmacodynamic profile in MDR-TB patients. We conclude that ertapenem is a highly promising drug for the treatment of MDR-TB that warrants further investigation.

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Section: Discussionsupporting

confidence: 93%

Pharmacokinetics of ertapenem in patients with multidrug-resistant tuberculosis

et al. 2016

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“…It is shown that the introduction of ertapenem intravenously at a dose of 1.0 after 8 hours ego concentration, determined at a microdialysis in the soft tissues in patients with DFIs did not differ from the registered concentration in healthy volunteers [45].…”

Section: Malorodova Tn Pokrovskaya Tg каZаkоvа Ee Urojevskaymentioning

confidence: 86%

Diabetic Foot Syndrome: Importance of Microbiological Monitoring and Antimicrobial Penetration of Chemotherapeutic Agents Into the Soft Tissue Lower Limb in Determining the Treatment

Malorodova¹,

Pokrovskaya²,

Kazakova³

et al. 2016

RR.P and CP

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“…The ertapenem penetration into soft tissue adjacent to a foot infection in diabetic patients was well comparable to these results. The unbound AUC in tissue divided by the total drug AUC in plasma was 8.3% for healthy tissue and 9.5% for inflamed tissue (29). Assuming a protein binding of 90% in plasma, this would translate into unbound AUC ratios of approximately 83% and 95%, respectively.…”

Section: Discussionmentioning

confidence: 99%

Population Pharmacokinetics and Target Attainment of Ertapenem in Plasma and Tissue Assessed via Microdialysis in Morbidly Obese Patients after Laparoscopic Visceral Surgery

Wittau

Paschke

Kurlbaum

et al. 2017

Antimicrob Agents Chemother

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Ertapenem provides broad-spectrum activity against many pathogens, and its use is relevant for the prophylaxis and treatment of infections in morbidly obese patients undergoing surgery. However, its pharmacokinetics and tissue penetration in these patients are not well defined. We assessed the population pharmacokinetics and target attainment for ertapenem in the plasma, subcutaneous tissue, and peritoneal fluid of morbidly obese patients. Six female patients (body mass index, 43.7 to 55.9 kg/m 2 ) received 1,000 mg ertapenem as 15-min infusions at 0 and 26 h. On day 2, the unbound ertapenem concentrations in plasma, subcutaneous tissue, and peritoneal fluid were measured by microdialysis; total plasma concentrations were additionally quantified. The probability of attaining a target of an unbound ertapenem concentration above the MIC for at least 40% of the dosing interval was predicted via Monte Carlo simulations. The population pharmacokinetic model contained two disposition compartments and simultaneously described all concentrations. For unbound ertapenem, total clearance was 12.3 liters/h (coefficient of variation, 21.6% for between-patient variability) and the volume of distribution at steady state was 57.8 liters in patients with a 53-kg fat-free mass. The area under the concentration-time curve (AUC) for ertapenem was 49% lower in subcutaneous tissue and 25% lower in peritoneal fluid than the unbound AUC in plasma. Tissue penetration was rapid (equilibration half-life, Ͻ15 min) and was variable in subcutaneous tissue. Short-term ertapenem infusions (1,000 mg every 24 h) achieved robust (Ͼ90%) target attainment probabilities for MICs of up to 1 mg/liter in plasma, 0.25 to 0.5 mg/liter in subcutaneous tissue, and 0.5 mg/liter in peritoneal fluid. Ertapenem presents an attractive choice for many pathogens relevant to morbidly obese patients undergoing surgery. (This study has been registered at ClinicalTrials.gov under identifier NCT01407965.) KEYWORDS ertapenem, morbidly obese patients, population pharmacokinetics, subcutaneous tissue, microdialysis, S-ADAPT, Monte Carlo simulation, pharmacodynamics E rtapenem covers many bacterial pathogens, and its use is relevant for the prophylaxis and treatment of infections in morbidly obese patients undergoing laparoscopic visceral surgery (1). Ertapenem has a relatively high level of protein binding

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Tissue pharmacokinetics of ertapenem at steady-state in diabetic patients with leg infections

Cited by 17 publications

References 27 publications

Pharmacokinetics of ertapenem in patients with multidrug-resistant tuberculosis

Pharmacokinetics of ertapenem in patients with multidrug-resistant tuberculosis

Diabetic Foot Syndrome: Importance of Microbiological Monitoring and Antimicrobial Penetration of Chemotherapeutic Agents Into the Soft Tissue Lower Limb in Determining the Treatment

Population Pharmacokinetics and Target Attainment of Ertapenem in Plasma and Tissue Assessed via Microdialysis in Morbidly Obese Patients after Laparoscopic Visceral Surgery

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