Population pharmacokinetics of daptomycin in patients affected by severe Gram-positive infections

Paolo, Antonello Di; Tascini, Carlo; Polillo, Marialuisa; Gemignani, G; Nielsen, Elisabet I.; Bocci, Guido; Karlsson, Mats O.; Menichetti, Francesco; Danesi, Romano

doi:10.1016/j.ijantimicag.2013.06.006

Cited by 51 publications

(45 citation statements)

References 28 publications

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“…The PK model, population parameter values, and covariates identified in this study are consistent with previous reports (2,4,5). In particular, our study and previous works have found that daptomycin clearance correlates with renal function, which is in agreement with the predominant renal excretion of the drug (9).…”

supporting

confidence: 92%

“…This probably affected the estimation of the interindividual variability, which was surprisingly low for CL and V 1 , about 5%, while previous studies reported coefficients of variations of 20% to 40% (2,4). It is noteworthy that these numbers reflect the interindividual variability that is unexplained by covariates, not the overall interindividual variability in CL and V 1 , which was larger (about 31% for CL and 19% for V 1 based on individual estimates on the first TDM occasion).…”

mentioning

confidence: 82%

“…The population pharmacokinetics (PK) of daptomycin have been described in various groups of patients in previous publications (2)(3)(4)(5). However, little information exists on the PK of daptomycin in patients with bone and joint infections (BJI).…”

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confidence: 99%

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Pharmacokinetic Variability of Daptomycin during Prolonged Therapy for Bone and Joint Infections

Goutelle

Roux

Gagnieu

et al. 2016

Antimicrob Agents Chemother

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The interindividual and intraindividual variabilities in daptomycin pharmacokinetics were investigated in 23 patients (69 pharmacokinetic profiles) who were treated for several months for bone and joint infections. Population daptomycin clearance was significantly influenced by renal function and was significantly higher in male than in female patients. We observed significant intraindividual changes in daptomycin clearance, which were uncorrelated with changes in renal function, suggesting that therapeutic drug monitoring is important in patients receiving prolonged daptomycin therapy. Daptomycin is a cyclic lipopeptide that has been proposed as an alternative therapeutic option in patients with prosthetic joint infection caused by Staphylococcus or Enterococcus species in the latest Infectious Diseases Society of America (IDSA) guidelines (1).The population pharmacokinetics (PK) of daptomycin have been described in various groups of patients in previous publications (2-5). However, little information exists on the PK of daptomycin in patients with bone and joint infections (BJI). Also, previous population studies did not investigate daptomycin PK over prolonged therapy, and, to our knowledge, no study has reported the intraindividual PK variability of this drug.(This work was presented in part at the 54th ICAAC Meeting, Washington, DC, 5 to 9 September 2014, and at the 34th RICAI meeting, Paris, France, 13 to 15 December 2014.)We performed a retrospective analysis of PK data collected in 23 patients who were treated with daptomycin for BJI in Lyon Center in 2012 and 2013. Therapeutic drug monitoring (TDM) of daptomycin was performed regularly in those patients throughout therapy, roughly every month, to ensure sufficient exposure and to prevent drug accumulation. This project was reviewed by our local institutional review board (CPP Sud-Est III), and a waiver was obtained, as this was a noninterventional study.On each TDM occasion, a daptomycin PK profile was obtained based on three concentrations usually measured at predose (trough level), 0.5 to 1 h, and 5 to 6 h postdose. A total of 203 daptomycin plasma concentrations and 69 individual PK profiles were determined for the 23 individuals. The exact daptomycin doses, dosing times, dose intervals, blood sampling times, and plasma concentrations were recorded for each subject on each occasion. All patients received daptomycin as a 30-min infusion. The dose interval was 24 h, except for 6 profiles from 4 patients in whom it was 48 h because of renal impairment. Other data available on each occasion included age, sex, height, weight, serum creatinine, estimated glomerular filtration rate (eGFR) provided by the 4-variable modification of diet in renal disease (MDRD) equation (6), and concomitant use of rifampin (10 profiles from 3 patients).Daptomycin concentrations were determined by using a highperformance liquid chromatography assay with a photodiode array detector. Concentrations were calculated at two wavelengths (260 and 360 nm), and a spectral analysis was ...

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confidence: 92%

mentioning

confidence: 82%

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Pharmacokinetic Variability of Daptomycin during Prolonged Therapy for Bone and Joint Infections

Goutelle

Roux

Gagnieu

et al. 2016

Antimicrob Agents Chemother

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“…To date, certain clinical groups have utilized TDM to optimize the dose of daptomycin for selected cases (9)(10)(11)(12). As with any nascent approach, a clearly defined system to measure and interpret daptomycin concentrations remains to be elucidated.…”

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confidence: 99%

Simplified Equations Using Two Concentrations To Calculate Area under the Curve for Antimicrobials with Concentration-Dependent Pharmacodynamics: Daptomycin as a Motivating Example

Pai

Russo

Novelli

et al. 2014

Antimicrob Agents Chemother

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The effects of several antimicrobial agents are predicted by the ratio of the area under the concentration-time curve (AUC) to the MIC (AUC/MIC). Peak (C p ) and trough (C t ) concentrations are often measured clinically as surrogates of AUC because actual computation of AUC from 1 or 2 samples requires sophisticated mathematical methods. Given that the effects of daptomycin are predicted by AUC/MIC, our objective was to compare simple equation calculated AUC based on C p and C t to model integrated AUC. A standard population pharmacokinetic model was used to simulate 5,000 daptomycin concentration-time profiles after 5 doses of 6 mg/kg of body weight/day (0.5-h infusions). The AUC for the 24-h period was computed by integration and by equations with 110 C p -C t combination pairs. The C p time points were in 15-min increments between 0.5 h and 3 h and C t in 15-min increments within an hour of the end of the dosing interval for each dose. The precision and bias of the calculated AUC relative to the integrated AUC were determined to identify C p -C t pairs associated with the lowest bias and highest precision. The equations were further validated using two daptomycin concentration-time data sets from healthy volunteers and critically ill patients. The precision and bias of calculated AUC were based primarily on C p , and use of a daptomycin C p 1.5 h to 3 h from the start of infusion was associated with a bias of <10% and an R 2 of >0.95. Data from the healthy volunteers and critically ill patients also demonstrated declining bias with use of C p >1.5 h from the start of infusion with relatively good precision. Simplified equations using a daptomycin C p approximately 2 h from the start of infusion and a C t within an hour of the end of the dosing interval should yield precise and unbiased estimates of daptomycin AUC.

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“…A population pharmacokinetic analysis, based on a nonlinear mixed-effects modelling approach, was conducted in order to predict the C min value in every patient. The NONMEM software, version 7.1 (ICON Development Solutions, Hanover, MD), and the Xpose and PsN packages were used to perform all the analyses as already described [8]. For the statistical analysis, means and standard deviations of means were calculated by standard methods.…”

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confidence: 99%

Reduced circulating B‐lymphocytes and altered B‐cell compartments in patients suffering from chronic myeloid leukaemia undergoing therapy with Imatinib

Carulli

Baratè

Marini

et al. 2014

Hematological Oncology

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Population pharmacokinetics of daptomycin in patients affected by severe Gram-positive infections

Cited by 51 publications

References 28 publications

Pharmacokinetic Variability of Daptomycin during Prolonged Therapy for Bone and Joint Infections

Pharmacokinetic Variability of Daptomycin during Prolonged Therapy for Bone and Joint Infections

Simplified Equations Using Two Concentrations To Calculate Area under the Curve for Antimicrobials with Concentration-Dependent Pharmacodynamics: Daptomycin as a Motivating Example

Reduced circulating B‐lymphocytes and altered B‐cell compartments in patients suffering from chronic myeloid leukaemia undergoing therapy with Imatinib

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