scholarly journals Population Pharmacokinetics and Dose Optimization of Teicoplanin during Venoarterial Extracorporeal Membrane Oxygenation

2017 ◽  
Vol 61 (9) ◽  
Author(s):  
Jin Wi ◽  
Hayeon Noh ◽  
Kyoung Lok Min ◽  
Seungwon Yang ◽  
Byung Hak Jin ◽  
...  
Keyword(s):  
Extracorporeal Membrane Oxygenation ◽  
Trough Concentration ◽  
Optimal Dose ◽  
Volume Of Distribution ◽  
Membrane Oxygenation ◽  
Venoarterial Extracorporeal Membrane Oxygenation ◽  
Optimal Dosing ◽  
Population Pk ◽  
Severe Infections ◽  
Central Volume

ABSTRACT The pharmacokinetics (PK) of drugs are known to be significantly altered in patients receiving extracorporeal membrane oxygenation (ECMO). However, clinical studies of the PK of drugs administered during ECMO are scarce, and the proper dosing adjustment has yet to be established. We developed a population PK model for teicoplanin, investigated covariates influencing teicoplanin exposure, and suggested an optimal dosing regimen for ECMO patients. Samples for PK analysis were collected from 10 adult patients, and a population PK analysis and simulations were performed to identify an optimal teicoplanin dose needed to provide a >50% probability of target attainment at 72 h using a trough concentration target of >10 μg/ml for mild to moderate infections and a trough concentration target of >15 μg/ml for severe infections. Teicoplanin was well described by a two-compartment PK model with first-order elimination. The presence of ECMO was associated with a lower central volume of distribution, and continuous renal replacement therapy (CRRT) was associated with a higher peripheral volume of distribution. For mild to moderate infections, an optimal dose was a loading dose (LD) of 600 mg and a maintenance dose (MD) of 400 mg for ECMO patients not receiving CRRT and an LD of 800 mg and an MD of 600 mg for those receiving CRRT. For severe infections, an optimal dose was an LD of 1,000 mg and an MD of 800 mg for ECMO patients not receiving CRRT and an LD of 1,200 mg and an MD of 1,000 mg for those receiving CRRT. In conclusion, doses higher than the standard doses are needed to achieve fast and appropriate teicoplanin exposure during ECMO. (This study has been registered at ClinicalTrials.gov under identifier NCT02581280.)

scholarly journals 1540. A Population Pharmacokinetic Model for Vancomycin in Korean Patients Receiving Extracorporeal Membrane Oxygenation Therapy: A Prospective Study

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S562-S562
Author(s):  
Younghee Jung ◽  
Dong-Hwan Lee ◽  
Hyoung Soo Kim
Keyword(s):  
Extracorporeal Membrane Oxygenation ◽  
Creatinine Clearance ◽  
Compartment Model ◽  
Volume Of Distribution ◽  
Population Pharmacokinetic ◽  
Test Model ◽  
Mixed Effect ◽  
Korean Patients ◽  
Membrane Oxygenation ◽  
Population Pk

Abstract Background There is no literature on population pharmacokinetics (PK) of vancomycin in Korean patients receiving extracorporeal membrane oxygenation (ECMO) therapy. The aim of this study was to develop a population PK model for vancomycin in Korean ECMO patients. Methods We prospectively enrolled adult patients who were undergoing ECMO and receiving vancomycin from July 2018 to April 2019. After initial dose of vancomycin was administrated, serial blood samples (seven to nine times per patient) were drawn before the next dose. A population PK model for vancomycin was developed using a nonlinear mixed-effect modeling. Age, sex, creatinine clearance, and body weight were tested as potential covariates in the model. Model selection was based on log-likelihood test, model diagnostic plots, and clinical plausibility. Results Fourteen patients were included over the period. Ten received venovenous, three venoarterial, and one both type ECMO. Eleven were men and the median age was 54 (interquartile range 45–66.3). Mean estimated glomerular filtration rate (eGFR) was 69 ± 46 mL/minute/1.73m2 by the modification of diet in renal disease equation. A total of 123 vancomycin concentrations from the patients were included in the analysis. The population PK of vancomycin was best described by a two-compartment model with a proportional residual error model. The typical value (%between-subject variability) for total clearance was estimated to be 4.33 L/h (21.6%), central volume of distribution was 9.22 L, the intercompartmental clearance was 10.75 L/hr (34.9%) and the peripheral volume of distribution was 19.6 L (26.6%). The proportional residual variability was 8.81%. Creatinine clearance significantly influenced vancomycin clearance (CL). The proposed equation to estimate vancomycin clearance in Korean ECMO patients was CL = 4.33 + 0.199 × (eGFR – 56). Conclusion A two-compartment population PK model successfully describes vancomycin PK profiles in Korean ECMO patients. The model could be used to optimize the dosing regimen if more data become available from currently ongoing clinical study. Disclosures All authors: No reported disclosures.

scholarly journals P67 Impact of enantiomer-specific maturational changes in pharmacokinetics on the racemic ketorolac target trough concentration

2019 ◽  
Vol 104 (6) ◽  
pp. e45.1-e45
Author(s):  
M Cloesmeijer ◽  
E Krekels ◽  
M van Esdonk ◽  
A Lynn ◽  
A Smits ◽  
...  
Keyword(s):  
Trough Concentration ◽  
Compartment Model ◽  
Volume Of Distribution ◽  
Plasma Samples ◽  
Analgesic Effects ◽  
Population Pk ◽  
Central Volume ◽  
Intravenous Ketorolac

IntroductionKetorolac is a racemic drug with analgesic effects specific to its S-enantiomer. This study aimed to describe enantiomer-specific maturational pharmacokinetics (PK). Simulations were performed to describe how S-ketorolac exposure in infants differs from adults, and how this affects the adult racemic analgesic trough threshold EC50 (EC50thr-adult, 0.37 mg/L) in infants (EC50thr-infant)when the same S-target is applied.MethodsA population PK analysis (NONMEM 7.3) was performed based on 1020 plasma samples from 5 studies including 80 patients (adults, children, infants) following single intravenous ketorolac administration.ResultsS-ketorolac PK was best described with a 2-compartment model in infants and 3-compartment model in adults, while R-ketorolac PK was best described with a 2-compartment model in all. S-ketorolac clearance [mean population value: 3.45 L/h/56 kg] and central volume of distribution (V1) [4.27 L/56kg] increased exponentially with bodyweight (0.75, 0.59 respectively). R-ketorolac clearance [0.93 L/h/56kg], peripheral volume of distribution (V2) and inter-compartmental clearance (Q) increased exponentially with bodyweight (0.62, 1.20, 0.76 respectively), V1 [4.11 L/56kg] linearly with bodyweight. Simulations revealed EC50thr-adult (0.37 mg/L) contained 0.048 mg/L S-ketorolac as mean in typical adults (BW 48.6–99.6 kg), while EC50thr-adult contained 0.032–0.036 mg/L S-ketorolac in typical infants (BW 5.3–10.6 kg). To reach adult S-enantiomer concentration (0.048 mg/L) in typical infants (BW 5.3–10.6 kg), EC50thr-infant should be 0.49–0.46 mg/L, respectively.ConclusionEnantiomer-specific maturational PK of ketorolac were described. Subsequent simulations displayed differences in proportion of S- and R-ketorolac on the racemic threshold EC50. A The same S-ketorolac concentration necessitates a higher EC50thr-infant to EC50thr-adult.Disclosure(s)Nothing to disclose

scholarly journals Population Pharmacokinetics of Caspofungin among Extracorporeal Membrane Oxygenation Patients during the Postoperative Period of Lung Transplantation

2020 ◽  
Vol 64 (11) ◽  
Author(s):  
Qianlin Wang ◽  
Zhu Zhang ◽  
Donglin Liu ◽  
Wenqian Chen ◽  
Gang Cui ◽  
...  
Keyword(s):  
Extracorporeal Membrane Oxygenation ◽  
Lung Transplantation ◽  
Postoperative Period ◽  
Compartment Model ◽  
Volume Of Distribution ◽  
Self Control ◽  
Control Group ◽  
Membrane Oxygenation ◽  
Population Pk ◽  
Before And After

ABSTRACT Little is known about the influence of extracorporeal membrane oxygenation (ECMO) on the pharmacokinetics (PK) of caspofungin. The aim of this study was to describe population PK of caspofungin in patients with and without ECMO during the postoperative period of lung transplantation (LTx) and to investigate covariates influencing caspofungin PK. We compared ECMO patients with non-ECMO patients, and patients before and after ECMO weaning as self-controls, to analyzed changes in caspofungin PK. Eight serial blood samples were collected from each patient for PK analysis. The population PK of caspofungin was described using nonlinear mixed-effects modeling. Twelve ECMO and 7 non-ECMO lung transplant recipients were enrolled in this study. None of the patients received renal replacement therapy during any part of the study period. The PK of caspofungin was best described by a two-compartment model. There were no significant differences in the PK parameters and concentrations of caspofungin among the ECMO, non-ECMO, and self-control group. In the final covariate model, we found that there was a significant association between the male gender and increased distribution volume, that a higher sequential organ failure assessment score was related to an increase in intercompartmental clearance, and that a longer operative time was related to an increase in clearance and the volume of distribution. ECMO did not have a significant impact on the PK of caspofungin in patients after LTx. Some factors were identified as statistically significant covariates related to the PK of caspofungin; however, their impact on clinical practice of caspofungin needs to be investigated further in more studies. (This study has been registered at ClinicalTrials.gov under identifier NCT03766282.)

Treatment of hyperammonemia using in-line renal replacement and hyperosmolar therapies within an extracorporeal membrane oxygenation circuit

Perfusion ◽  
2021 ◽  
pp. 026765912110359
Author(s):  
Alison Grazioli ◽  
Jamie E Podell ◽  
Aldo Iacono ◽  
Alexander Sasha Krupnik ◽  
Ronson J Madathil ◽  
...  
Keyword(s):  
Extracorporeal Membrane Oxygenation ◽  
Cerebral Edema ◽  
Urea Cycle ◽  
Rare Complication ◽  
Volume Of Distribution ◽  
Intermittent Hemodialysis ◽  
Treatment Goals ◽  
Continuous Venovenous Hemofiltration ◽  
Small Molecular Weight ◽  
Membrane Oxygenation

After orthotopic lung transplantation, hyperammonemia can be a rare complication secondary to infection by organisms that produce urease or inhibit the urea cycle. This can cause neurotoxicity, cerebral edema, and seizures. Ammonia is unique in that it has a large volume of distribution. However, it is also readily dialyzable given its small molecular weight. As such, removal of ammonia requires renal replacement modalities that can both rapidly remove ammonia from the plasma space and allow for continuous removal to prevent rebound accumulation from intracellular stores. Prevention of iatrogenic osmotic lowering in this setting is required to prevent worsening of cerebral edema. Herein, we describe use of sequential in-line renal replacement therapy using both intermittent hemodialysis and continuous venovenous hemofiltration within an extracorporeal membrane oxygenation circuit in conjunction with higher sodium dialysate and 7.5% hypertonic saline to achieve these treatment goals.

Sign in / Sign up

Export Citation Format

Share Document