scholarly journals Pharmacometric approach to assist dosage regimen design in neonates undergoing therapeutic hypothermia

2021 ◽  
Author(s):  
Saikumar Matcha ◽  
Elstin Anbu Raj ◽  
Ramya Mahadevan ◽  
Arun Prasath Raju ◽  
V Rajesh ◽  
...  
Keyword(s):  
Birth Weight ◽  
Serum Creatinine ◽  
Therapeutic Hypothermia ◽  
Dosage Regimen ◽  
Perinatal Asphyxia ◽  
Systematic Search ◽  
Optimal Dosage ◽  
Suitable Model ◽  
List Type ◽  
Optimal Dosage Regimen

Abstract Background Therapeutic hypothermia (TH) is the treatment of choice for neonates diagnosed with perinatal asphyxia (PA). Dosing recommendations of various therapeutic agents including antimicrobials were not specifically available for the neonates undergoing TH. Methods A systematic search methodology was used to identify pharmacokinetic (PK) studies of antimicrobials during TH. Antimicrobials with multiple PK studies were identified to create a generalizable PK model. Pharmacometric simulations were performed using the PUMAS software platform to reproduce the results of published studies. A suitable model that could reproduce the results of all other published studies was identified. With the help of a generalizable model, an optimal dosage regimen was designed considering the important covariates of the identified model. Results With the systematic search, only gentamicin had multiple PK reports during TH. A generalizable model was identified and the model predictions could match the reported/observed concentrations of publications. Birth weight and serum creatinine were the significant covariates influencing the PK of gentamicin in neonates. A dosage nomogram was designed using pharmacometric simulations to maintain gentamicin concentrations below 10 μg/mL at peak and below 2 μg/mL at trough. Conclusions A generalizable PK model for gentamicin during TH in neonates was identified. Using the model, a dosing nomogram for gentamicin was designed. Impact Dosing guidelines for antimicrobials during TH in neonates is lacking. This is the first study to identify the generalizable model for gentamicin during TH in neonates. Nomogram, proposed in the study, will aid the clinicians to individualize gentamicin dosing regimen for neonates considering the birth weight and serum creatinine.

scholarly journals Population pharmacokinetic analysis and dose regimen optimization in Japanese infants with an extremely low birth weight

2020 ◽  
pp. AAC.02523-20
Author(s):  
Hiroshi Sasano ◽  
Kanon Aoki ◽  
Ryutarou Arakawa ◽  
Kazuhiko Hanada
Keyword(s):  
Body Weight ◽  
Birth Weight ◽  
Low Birth Weight ◽  
Dosage Regimen ◽  
Extremely Low Birth Weight ◽  
Pharmacokinetic Data ◽  
Optimal Dosage ◽  
Low Birth Weight Infants ◽  
Final Model ◽  
Optimal Dosage Regimen

Vancomycin is a synthetic antibiotic effective against gram-positive pathogens. Although the clinical applicability of vancomycin for infants has been increasing, the pharmacokinetic data of vancomycin in extremely low-birth-weight infants are limited. The aim of this study was to construct a population pharmacokinetics model for vancomycin in extremely low-birth-weight infants and establish an optimal dosage regimen. We enrolled children aged less than 1 yr with a birth weight of less than 1000 g and body weight at vancomycin prescription of less than 1500 g. Pharmacokinetic data from 19 patients were analyzed and a population pharmacokinetics model was developed using nonlinear mixed-effects modeling software. Goodness-of-fit plots, a nonparametric bootstrap analysis, and a prediction-corrected visual predictive check were employed to evaluate the final model. The dosage regimen was optimized based on the final model. The pharmacokinetic data fit a one-compartment model with first-order elimination, and body weight and estimated serum creatinine level were used as significant covariates. In a simulation using the final model, the optimal dosage regimen, especially when the serum creatinine level (>0.6 mg/dL) was high, was 5.0–7.5 mg/kg twice a day every 12 h; this was required to reduce the dosage compared with that in previous studies. The recommended doses based on the current target time-course concentration curves may not be appropriate for extremely low-birth-weight infants.

scholarly journals Optimization of Dosage Regimen of Meropenem in Patients Undergoing Venoarterial Extracorporeal Membrane Oxygenation: A Prospective Cohort Study

2021 ◽  
Author(s):  
Soyoung Kang ◽  
Seungwon Yang ◽  
Jongsung Hahn ◽  
June Young Jang ◽  
Kyoung Lok Min ◽  
...  
Keyword(s):  
Cohort Study ◽  
Dosage Regimen ◽  
Population Pharmacokinetic Model ◽  
Pharmacokinetic Model ◽  
Volume Of Distribution ◽  
Population Pharmacokinetic ◽  
Optimal Dosage ◽  
Optimal Dosage Regimen ◽  
Venoarterial Extracorporeal Membrane Oxygenation ◽  
Va Ecmo

Abstract BackgroundPatients receiving venoarterial extracorporeal membrane oxygenation (VA ECMO) therapy often require antibiotics to prevent and treat infections. Our objective was to determine an optimal dosage regimen of meropenem in patients receiving VA ECMO by developing a population pharmacokinetic model.MethodsThis was a prospective cohort study. Blood samples were collected during ECMO (ECMO-ON) and after ECMO (ECMO-OFF). The population pharmacokinetic model was developed using nonlinear mixed-effects modelling. A Monte Carlo simulation was used (n=10,000) to assess the probability of target attainment.ResultsThirteen adult patients on ECMO receiving meropenem were included. Meropenem pharmacokinetics was best fitted by a two-compartment model. Covariate analysis indicated that continuous renal replacement therapy (CRRT) was negatively correlated with clearance (CL). The final pharmacokinetic model was: CL (L/h) = 3.79 × 0.44CRRT; where use of CRRT = 1, no CRRT = 0, central volume of distribution (L) = 2.4, peripheral volume of distribution (L) = 8.56, and intercompartmental clearance (L/h) = 21.3. According to the simulation results, 1–2 g q8h intravenous administration over 20 min was sufficient in patients without CRRT for both susceptible (minimum inhibitory concentration (MIC) = 2 mg/L) and resistant (MIC = 8 mg/L) pathogens, regardless of ECMO use (40% fT>MIC target). However, if more aggressive treatment is needed (100% fT>MIC target), dose increment or extended infusion is recommended.ConclusionsWe established a population pharmacokinetic model for meropenem in patients receiving VA ECMO and suggested an optimal dosage regimen. These results should improve treatment success and survival in VA ECMO patients. Clinicaltrials.gov registration # NCT02581280

scholarly journals Determination of Susceptibility Breakpoint for Cefquinome against Streptococcus suis in Pigs

Antibiotics ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 958
Author(s):  
Kun Mi ◽  
Mei Li ◽  
Lei Sun ◽  
Yixuan Hou ◽  
Kaixiang Zhou ◽  
...  
Keyword(s):  
Dosage Regimen ◽  
Ex Vivo ◽  
Clinical Effectiveness ◽  
Streptococcus Suis ◽  
Pharmacokinetic Parameters ◽  
Optimal Dosage ◽  
Human Beings ◽  
Integration Model ◽  
Optimal Dosage Regimen ◽  
Susceptibility Breakpoint

Streptococcus suis (S. suis), a zoonotic pathogen, causes severe diseases in both pigs and human beings. Cefquinome can display excellent antibacterial activity against gram-negative and gram-positive bacteria. The aim of this study was to derive an optimal dosage of cefquinome against S. suis with a pharmacokinetic/pharmacodynamic (PK/PD) integration model in the target infection site and to investigate the cutoffs monitoring the changes of resistance. The minimum inhibitory concentration (MIC) distribution of cefquinome against 342 S. suis strains was determined. MIC50 and MIC90 were 0.06 and 0.25 μg/mL, respectively. The wild-type cutoff was calculated as 1 μg/mL. A two-compartmental model was applied to calculate the main pharmacokinetic parameters after 2 mg/kg cefquinome administered intramuscularly. An optimized dosage regimen of 3.08 mg/kg for 2-log10 CFU reduction was proposed by ex vivo PK/PD model of infected swine. The pharmacokinetic-pharmacodynamic cutoff was calculated as 0.06 μg/mL based on PK/PD targets. Based on the clinical effectiveness study of pathogenic MIC isolates, the clinical cutoff was calculated as 0.5 μg/mL. A clinical breakpoint was proposed as 1 μg/mL. In conclusion, the results offer a reference for determining susceptibility breakpoint of cefquinome against S. suis and avoiding resistance emergence by following the optimal dosage regimen.

scholarly journals Vancomycin prophylaxis in cardiac operations: Determination of an optimal dosage regimen

1983 ◽  
Vol 85 (6) ◽  
pp. 933-935 ◽  
Author(s):  
Bruce F. Farber ◽  
Adolf W. Karchmer ◽  
Mortimer J. Buckley ◽  
Robert C. Moellering
Keyword(s):  
Dosage Regimen ◽  
Optimal Dosage ◽  
Optimal Dosage Regimen ◽  
Cardiac Operations

Optimal Dosage Regimen of Meropenem for Pediatric Patients Based on Pharmacokinetic/Pharmacodynamic Considerations

2011 ◽  
Vol 26 (5) ◽  
pp. 523-531 ◽  
Author(s):  
Yuka Ohata ◽  
Yoshiko Tomita ◽  
Mitsunobu Nakayama ◽  
Tsuneo Kozuki ◽  
Keisuke Sunakawa ◽  
...  
Keyword(s):  
Dosage Regimen ◽  
Pediatric Patients ◽  
Optimal Dosage ◽  
Optimal Dosage Regimen

scholarly journals INCIDENCE AND CAUSES OF ACUTE KIDNEY INJURY IN SICK NEONATE : A STUDY FROM A TERTIARY CARE NEONATAL UNIT

2020 ◽  
pp. 1-2
Author(s):  
Krishnendu Karmakar ◽  
Sumanta Laha ◽  
Bhaswati Ghoshal ◽  
Pradip Kumar Das
Keyword(s):  
Acute Kidney Injury ◽  
Birth Weight ◽  
Kidney Disease ◽  
Serum Creatinine ◽  
Perinatal Asphyxia ◽  
Tertiary Care ◽  
Kidney Injury ◽  
Care Hospital ◽  
Cross Sectional ◽  
Normal Birth

Objective To find out the incidence of Acute Kidney Injury(AKI) and various causes responsible for the AKI in sick neonates in a tertiary care hospital. Material and Method In this observational cross sectional study we included all neonates with features suggestive of AKI with exclusion criteria of extreme prematurity, chronic kidney disease and major congenital anomaly. We diagnose AKI according to the KIDIGO(Kidney Disease: Improving Global Outcome)guideline where we take serum creatinine value and urinary output as determinant. Serum creatinine value measured at 48 and 72 hrs of admission and repeated at 96 hrs if there is rising trend of creatinine..Now we find out the incidence of AKI in relation to gender, birth weight, mode of delivary . Among the AKI case we sort out the causative factors like perinatal asphyxia,sepsis, shock, prematurity etc and analysed all the results statistically. Results Out of total 1872 neonates admitted during the 18 months study period we found AKI in 111 neonates(5.93%).There is male preponderance and most neonates are of normal birth wt.Among the various causes of AKI perinatal asphyxia is the leading cause followed by sepsis and prematurity.Other imp causes are congenital heart disease,shock, PPHN , nephrotoxic drug use and RDS of newborn. We found asphyxia as the leading cause of AKI in normal vaginal delivary group whereas sepsis is the main cause of AKI in cesarean section group. Conclusion AKI is fairly common in sick neonates , even in normal birth weight babies and perinatal asphyxia and sepsis are the two most prevalent cause for AKI in this study.

scholarly journals Evaluation of Serum Concentrations Achieved With an Empiric Once-Daily Tobramycin Dosage Regimen in Children and Adults With Cystic Fibrosis

2012 ◽  
Vol 17 (1) ◽  
pp. 67-77
Author(s):  
Heather L VandenBussche ◽  
Douglas N Homnick
Keyword(s):  
Cystic Fibrosis ◽  
Adverse Effects ◽  
Dosage Regimen ◽  
Parent Satisfaction ◽  
Forced Expiratory Volume ◽  
Ease Of Use ◽  
Optimal Dosage ◽  
Serum Concentrations ◽  
Once Daily ◽  
Optimal Dosage Regimen

OBJECTIVES To assess the ability of an empiric once-daily dosing (ODD) tobramycin regimen to achieve desired serum concentrations in patients with cystic fibrosis (CF); to determine an optimal dosage regimen, using pharmacodynamic parameters; and to evaluate clinical response, adverse effects, and patient/parent satisfaction with ODD. METHODS This was a prospective single-center trial in patients with CF who are 5 years of age and older requiring intravenous antibiotics. Tobramycin, 10 mg/kg every 24 hours, was infused over 60 minutes, and two serum concentrations were analyzed using 1-compartment pharmacokinetic modeling. Simulations were performed to identify dosage regimens that maximized desired pharmacodynamic parameters. Other data included demographics, symptoms, spirometry, adverse events, and satisfaction with ODD. RESULTS A total of 14 children and 11 adults completed the study. Empiric doses resulted in mean peak tobramycin concentrations of 28.7 ± 5.5 mg/L and undetectable trough concentrations. Only 42% of patients achieved desired peak serum concentrations (20-30 mg/L) with the empiric regimen. A regimen of 12 mg/kg every 24 hours would achieve modified pharmacodynamic goals with an acceptable peak range of 20 to 35 mg/L. Forced expiratory volume in 1 second improved in 15 of 20 (75%) patients with ODD. Two patients experienced reversible vestibular adverse effects attributed to tobramycin. All patients were satisfied or very satisfied with ODD because of convenience and ease of use. CONCLUSIONS An empiric tobramycin regimen of 10 mg/kg every 24 hours did not achieve desired serum concentrations for most patients, although all patients demonstrated clinical improvement. Desired tobramycin concentrations with modified pharmacodynamic goals could be achieved by using an empiric dosage of 12 mg/kg every 24 hours. Prospective evaluation of this regimen with individualized patient monitoring is needed to ensure safety and efficacy and to monitor the effects on microbial resistance patterns.

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