Perioperative Pharmacodynamics of Acetaminophen Analgesia in Children 

1999 ◽  
Vol 90 (2) ◽  
pp. 411-421 ◽  
Author(s):  
Brian J. Anderson ◽  
Nicholas H. G. Holford ◽  
Gerald A. Woollard ◽  
Suchitra Kanagasundaram ◽  
Murali Mahadevan
Keyword(s):  
Coefficient Of Variation ◽  
Half Life ◽  
Lag Time ◽  
Hill Coefficient ◽  
Pharmacokinetic Parameters ◽  
Effect Compartment ◽  
Population Pharmacokinetic ◽  
Parameter Estimates ◽  
First Order ◽  
Emax Model

Background There are no adequate pharmacodynamic data relating concentrations of acetaminophen in serum to analgesia. Methods Children undergoing outpatient tonsillectomy were administered acetaminophen either orally, 0.5-1.0 h preoperatively (n = 20), or per rectum at induction of anesthesia (n = 100). No other analgesic agents were administered. Individual concentrations of acetaminophen in serum and pain scores (0-10) measured over a 4-h postoperative period were analyzed using a nonlinear mixed-effects model (NONMEM). Results Mean (% CV) estimates of population pharmacokinetic parameters with percent coefficient of variation, standardized to a 70-kg person, for a one-compartment model with first-order input, lag time, and first order-elimination were a volume of distribution of 60 (21) 1 and a clearance of 13.5 (46) 1/h. Rectally administered acetaminophen had an absorption half-life of 35 (63) min with a lag time of 40 min. The absorption half-life for the oral preparation was 4.5 (63) min without a detectable lag time. The relative bioavailability of the rectal compared with the oral formulation was 0.54. The equilibration half-time of an effect compartment was 1.6 (131) h. Pharmacodynamic population parameter estimates (percent coefficient of variation) for a fractional sigmoidal Emax model, in which the greatest possible pain relief equates to an Emax of 1, were Emax = 1, EC50 (the concentration producing 50% of Emax) = 3.4 (94) mg/l, and Hill coefficient = 0.54 (42). Conclusions The pharmacodynamics of acetaminophen can be described using a sigmoidal Emax model with a low Hill coefficient. To achieve a mean posttonsillectomy pain score of 3.6 of 10, an effect compartment concentration of 10 mg/l is necessary.

Acetaminophen Developmental Pharmacokinetics in Premature Neonates and Infants

2002 ◽  
Vol 96 (6) ◽  
pp. 1336-1345 ◽  
Author(s):  
Brian J. Anderson ◽  
Richard A. van Lingen ◽  
Tom G. Hansen ◽  
Yuan-Chi Lin ◽  
Nicholas H. G. Holford
Keyword(s):  
Half Life ◽  
Lag Time ◽  
Volume Of Distribution ◽  
Pharmacokinetic Analysis ◽  
Population Pharmacokinetic ◽  
Parameter Estimates ◽  
Nonlinear Mixed Effects Models ◽  
Premature Neonates ◽  
First Order ◽  
Neonates And Infants

Background The aim of this study was to describe acetaminophen developmental pharmacokinetics in premature neonates through infancy to suggest age-appropriate dosing regimens. Methods A population pharmacokinetic analysis of acetaminophen time-concentration profiles in 283 children (124 aged < or = 6 months) reported in six studies was undertaken using nonlinear mixed-effects models. Neonates and infants were given either single or multiple doses of four different formulations: oral elixir, rectal solution, or triglyceride or capsular suppository. The median postnatal age of children younger than 6 months was 1 day (range, birth to 6 months), median postconception age was 40 weeks (range, 28-64 weeks), and median weight was 3.1 kg (range, 1.2-9.0 kg). Results Population pharmacokinetic parameter estimates and their variability (percent) for a one-compartment model with first-order input, lag time, and first-order elimination were as follows: volume of distribution, 66.6 l (20%); clearance, 12.5 l/h (44%); standardized to a 70-kg person using allometric "1/4 power" models. The volume of distribution decreased exponentially with a maturation half-life of 11.5 weeks from 109.7 l/70 kg at 28 weeks after conception to 72.9 l/70 kg by 60 weeks. Clearance increased from 28 weeks after conception (0.74 l x h(-1) x 70 kg(-1)) with a maturation half-life of 11.3 weeks to reach 10.8 l x h(-1) x 70 kg(-1) by 60 weeks. The absorption half-life for the oral elixir preparation was 0.21 h (120%) with a lag time of 0.42 h (70%), but absorption was further delayed (2 h) in premature neonates in the first few days of life. Absorption half-life parameters for the triglyceride base and capsule suppositories were 0.80 h (100%) and 1.4 h (57%), respectively. The absorption half-life for the rectal solution was 0.33 h. Absorption lag time was negligible by the rectal route for all three formulations. The bioavailability of the capsule suppository relative to elixir decreased with age from 0.92 (22%) at 28 weeks after conception to 0.86 at 2 yr of age, whereas the triglyceride base decreased from 0.86 (35%) at 28 weeks postconception to 0.5 at 2 yr of age. The relative bioavailability of the rectal solution was 0.66. Conclusions A mean steady state target concentration greater than 10 mg/l at trough can be achieved by an oral dose of 25 mg x kg(-1) x d(-1) in premature neonates at 30 weeks' postconception, 45 mg x kg(-1) x d(-1) at 34 weeks' gestation, 60 mg x kg(-1) x d(-1) at term, and 90 mg x kg(-1) x d(-1) at 6 months of age. The relative rectal bioavailability is formulation dependent and decreases with age. Similar concentrations can be achieved with maintenance rectal doses of 25 (capsule suppository) or 30 (triglyceride suppository) mg. kg-1. d-1 in premature neonates at 30 weeks' gestation, increasing to 90 (capsule suppository) or 120 (triglyceride suppository) mg x kg(-1) x d(-1) at 6 months. These regimens may cause hepatotoxicity in some individuals if used for longer than 2-3 days.

scholarly journals 1319. Pharmacokinetics of Ceftolozane/Tazobactam in Patients with Burns

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S670-S671
Author(s):  
Ronald G Hall ◽  
Jotam Pasipanodya ◽  
William C Putnam ◽  
John Griswold ◽  
Sharmila Dissanaike ◽  
...  
Keyword(s):  
Human Plasma ◽  
Kidney Injury ◽  
Compartment Model ◽  
Pharmacokinetic Parameters ◽  
Therapeutic Drug ◽  
Population Pharmacokinetic ◽  
Parameter Estimates ◽  
Population Parameter ◽  
Full Thickness ◽  
Severe Burns

Abstract Background Antimicrobial dosing in moderate/severe burns patients is complicated due to the potential unpredictable hyperdynamic pathophysiologic states including 1) hypoproteinemia, 2) acute kidney injury and 3) onset of septicemia. Therefore, distribution assumptions about the population pharmacokinetic (PopPK) profiles of either endogenous or xenobiotic pharmacophores in this patient population can lead to biased parameter estimates. In order to prevent potential bias an agnostic nonparametric adaptive grid approach to describe ceftolozane/tazobactam (C/T) PopPK profiles in patients with partial- and full-thickness burns was employed. Methods A human clinical PK study in burn patients was conducted using the standard approved dose of C/T (2 grams/1 gram). A single intravenous dose was administered over 60 minutes. Whole blood was obtained pre-dose and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, and 24 hours following the start of infusion. LC-MS/MS bioanalytical methods were developed, validated and employed to determine C/T concentrations in human plasma. PopPK were modeled using Pmetrics package for R. One-, two- and three-compartment models were examined and compared. The influence of several parameters, including %body surface area burns, creatinine clearance (CrCL), weight, albumin and age were tested. Results The bioanalytical method for determination of C/T in human plasma met all recommended criteria of the LC-MS/MS. Five males and one female (ages 24 to 66 years), contributed 148 plasma PK samples. The female had 35% partial-thickness burns. The males had full-thickness burns ranging from 27 to 66%. The median CrCL was 104 mL/min (range 73-148 mL/min). Two-compartment model with absorption (Ka) from compartment 1 to 2 and elimination from compartment 2 (Ke), with nonlinear interactions between C/T elimination and CrCL best described the data. Figure A show that bias was minimal. Importantly, both drugs exhibited marked variability for both volume and elimination (Table), since volume was bimodally distributed (Figure B). A) Observation-versus-Prediction; B) Estimated Ke, V and Ka population parameter densities Summary of pharmacokinetic parameters Conclusion C/T exhibited high variability surpassing that observed with severe infections, suggesting that dose adjustment and/or may be therapeutic drug monitoring may be needed to balance target attainment from dose-related toxicities. Disclosures Ronald G. Hall, II, PharmD, MSCS, Medical Titan Group (Grant/Research Support)Merck (Research Grant or Support)

scholarly journals Population Pharmacokinetic Analysis of Voriconazole and Anidulafungin in Adult Patients with Invasive Aspergillosis

2014 ◽  
Vol 58 (8) ◽  
pp. 4718-4726 ◽  
Author(s):  
Ping Liu ◽  
Diane R. Mould
Keyword(s):  
Invasive Aspergillosis ◽  
Area Under The Curve ◽  
Compartment Model ◽  
Population Pharmacokinetic Analysis ◽  
Institutional Review Boards ◽  
Pharmacokinetic Analysis ◽  
Population Pharmacokinetic ◽  
Parameter Estimates ◽  
First Order ◽  
Two Compartment Model

ABSTRACTTo assess the pharmacokinetics (PK) of voriconazole and anidulafungin in patients with invasive aspergillosis (IA) in comparison with other populations, sparse PK data were obtained for 305 adults from a prospective phase 3 study comparing voriconazole and anidulafungin in combination versus voriconazole monotherapy (voriconazole, 6 mg/kg intravenously [IV] every 12 h [q12h] for 24 h followed by 4 mg/kg IV q12h, switched to 300 mg orally q12h as appropriate; with placebo or anidulafungin IV, a 200-mg loading dose followed by 100 mg q24h). Voriconazole PK was described by a two-compartment model with first-order absorption and mixed linear and time-dependent nonlinear (Michaelis-Menten) elimination; anidulafungin PK was described by a two-compartment model with first-order elimination. For voriconazole, the normal inverse Wishart prior approach was implemented to stabilize the model. Compared to previous models, no new covariates were identified for voriconazole or anidulafungin. PK parameter estimates of voriconazole and anidulafungin are in agreement with those reported previously except for voriconazole clearance (the nonlinear clearance component became minimal). At a 4-mg/kg IV dose, voriconazole exposure tended to increase slightly as age, weight, or body mass index increased, but the difference was not considered clinically relevant. Estimated voriconazole exposures in IA patients at 4 mg/kg IV were higher than those reported for healthy adults (e.g., the average area under the curve over a 12-hour dosing interval [AUC0–12] at steady state was 46% higher); while it is not definitive, age and concomitant medications may impact this difference. Estimated anidulafungin exposures in IA patients were comparable to those reported for the general patient population. This study was approved by the appropriate institutional review boards or ethics committees and registered on ClinicalTrials.gov (NCT00531479).

Validation of Population Pharmacokinetic Parameters of Phenytoin Using the Parallel Michaelis-Menten and First-Order Elimination Model

2000 ◽  
Vol 22 (3) ◽  
pp. 313-319 ◽  
Author(s):  
Praneet N. Valodia ◽  
Michael A. Seymour ◽  
Margaret L. McFadyen ◽  
Raymond Miller ◽  
Peter I. Folb
Keyword(s):  
Pharmacokinetic Parameters ◽  
Population Pharmacokinetic ◽  
First Order

scholarly journals Population Pharmacokinetics of Atazanavir in Patients with Human Immunodeficiency Virus Infection

2006 ◽  
Vol 50 (11) ◽  
pp. 3801-3808 ◽  
Author(s):  
Sara Colombo ◽  
Thierry Buclin ◽  
Matthias Cavassini ◽  
Laurent A. Décosterd ◽  
Amalio Telenti ◽  
...  
Keyword(s):  
Plasma Levels ◽  
Population Analysis ◽  
Pharmacokinetic Profile ◽  
Relative Bioavailability ◽  
Fixed Dose ◽  
Pharmacokinetic Parameters ◽  
Therapeutic Drug ◽  
Population Pharmacokinetic ◽  
Parameter Estimates ◽  
Genetic Traits

ABSTRACT Atazanavir (ATV) is a new azapeptide protease inhibitor recently approved and currently used at a fixed dose of either 300 mg once per day (q.d.) in combination with 100 mg ritonavir (RTV) or 400 mg q.d. without boosting. ATV is highly bound to plasma proteins and extensively metabolized by CYP3A4. Since ATV plasma levels are highly variable and seem to be correlated with both viral response and toxicity, dosage individualization based on plasma concentration monitoring might be indicated. This study aimed to assess the ATV pharmacokinetic profile in a target population of HIV patients, to characterize interpatient and intrapatient variability, and to identify covariates that might influence ATV disposition. A population analysis was performed with NONMEM with 574 plasma samples from a cohort of 214 randomly selected patients receiving ATV. A total of 346 randomly collected ATV plasma levels and 19 full concentration-time profiles at steady state were available. The pharmacokinetic parameter estimates were an oral clearance (CL) of 12.9 liters/h (coefficient of variation [CV], 26%), a volume of distribution of 88.3 liters (CV, 29%), an absorption rate constant of 0.405 h−1 (CV, 122%), and a lag time of 0.88 h. A relative bioavailability value was introduced to account for undercompliance due to infrequent follow-ups (0.81; CV, 45%). Among the covariates tested, only RTV significantly reduced CL by 46%, thereby increasing the ATV elimination half-life from 4.6 h to 8.8 h. The pharmacokinetic parameters of ATV were adequately described by a one-compartment population model. The concomitant use of RTV improved the pharmacokinetic profile. However, the remaining high interpatient variability suggests the possibility of an impact of unmeasured covariates, such as genetic traits or environmental influences. This population pharmacokinetic model, together with therapeutic drug monitoring and Bayesian dosage adaptation, can be helpful in the selection and adaptation of ATV doses.

Interpretation of Simulation Studies for Efficient Estimation of Population Pharmacokinetic Parameters

1993 ◽  
Vol 27 (9) ◽  
pp. 1034-1039 ◽  
Author(s):  
Ene I. Ette ◽  
Andrew W. Kelman ◽  
Catherine A. Howie ◽  
Brian Whiting
Keyword(s):  
Parameter Estimation ◽  
Efficient Estimation ◽  
Experimental Unit ◽  
Pharmacokinetic Parameters ◽  
Population Pharmacokinetic ◽  
Parameter Estimates ◽  
Model Parameters ◽  
Good Precision ◽  
Simulation Studies ◽  
Individual Parameter

OBJECTIVE: To develop new approaches for evaluating results obtained from simulation studies used to determine sampling strategies for efficient estimation of population pharmacokinetic parameters. METHODS: One-compartment kinetics with intravenous bolus injection was assumed and the simulated data (one observation made on each experimental unit [human subject or animal]), were analyzed using NONMEM. Several approaches were used to judge the efficiency of parameter estimation. These included: (1) individual and joint confidence intervals (CIs) coverage for parameter estimates that were computed in a manner that would reveal the influence of bias and standard error (SE) on interval estimates; (2) percent prediction error (%PE) approach; (3) the incidence of high pair-wise correlations; and (4) a design number approach. The design number (Φ) is a new statistic that provides a composite measure of accuracy and precision (using SE). RESULTS: The %PE approach is useful only in examining the efficiency of estimation of a parameter considered independently. The joint CI coverage approach permitted assessment of the accuracy and reliability of all model parameter estimates. The Φ approach is an efficient method of achieving an accurate estimate of parameter(s) with good precision. Both the Φ for individual parameter estimation and the overall Φ for the estimation of model parameters led to optimal experimental design. CONCLUSIONS: Application of these approaches to the analyses of the results of the study was found useful in determining the best sampling design (from a series of two sampling times designs within a study) for efficient estimation of population pharmacokinetic parameters.

scholarly journals Pharmacokinetics of Dihydroartemisinin and Piperaquine in Pregnant and Nonpregnant Women with Uncomplicated Falciparum Malaria

2011 ◽  
Vol 55 (12) ◽  
pp. 5500-5506 ◽  
Author(s):  
Marcus J. Rijken ◽  
Rose McGready ◽  
Aung Phae Phyo ◽  
Niklas Lindegardh ◽  
Joel Tarning ◽  
...  
Keyword(s):  
Pregnant Women ◽  
Falciparum Malaria ◽  
Half Life ◽  
Drug Exposure ◽  
Venous Blood ◽  
Uncomplicated Falciparum Malaria ◽  
Fixed Dose ◽  
Pharmacokinetic Parameters ◽  
Population Pharmacokinetic ◽  
Population Pharmacokinetic Modeling

ABSTRACTDihydroartemisinin-piperaquine is a fixed-dose artemisinin-based combination treatment. Some antimalarials have altered pharmacokinetics in pregnancy. Pregnant women in the 2nd or 3rd trimester and matched nonpregnant women with uncomplicated falciparum malaria were treated with a total of 6.4 mg/kg of body weight dihydroartemisinin and 51.2 mg/kg piperaquine once daily for 3 days. Venous blood samples were drawn at prespecified time points over 9 weeks. Plasma dihydroartemisinin and piperaquine concentrations were analyzed by liquid chromatography-mass spectrometry. Piperaquine and dihydroartemisinin pharmacokinetics were well described. There were no significant differences in total piperaquine exposure (P= 0.80) or drug exposure during the terminal elimination phase (72 h to infinity) (P= 0.64) between the two groups. The apparent volume of distribution of piperaquine was significantly smaller (602 liters/kg versus 877 liters/kg) in pregnant women than in nonpregnant women (P= 0.0057), and the terminal elimination half-life was significantly shorter (17.8 days versus 25.6 days;P= 0.0023). Dihydroartemisinin exposure after the first dose was significantly lower (844 h × ng/ml versus 1,220 h × ng/ml,P= 0.0021) in pregnant women, but there were no significant differences in total dihydroartemisinin exposure or maximum concentrations between the two groups. There were no significant differences in any pharmacokinetic parameters between the second and third trimester. These results obtained through noncompartmental analysis suggest that in the treatment of falciparum malaria, there are no clinically important differences in the pharmacokinetics of dihydroartemisinin or piperaquine between pregnant and nonpregnant women. However, a more detailed analysis using population pharmacokinetic modeling is needed to fully investigate the differences found for some of the pharmacokinetic parameters, such as the terminal half-life.

Lack of relationship between systemic exposure for the component drug of the fluorouracil, epirubicin, and 4-hydroxycyclophosphamide regimen in breast cancer patients.

1996 ◽  
Vol 14 (5) ◽  
pp. 1581-1588 ◽  
Author(s):  
M Sandström ◽  
A Freijs ◽  
R Larsson ◽  
P Nygren ◽  
M L Fjällskog ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Half Life ◽  
Systemic Exposure ◽  
Compartment Model ◽  
Pharmacokinetic Parameters ◽  
Therapeutic Drug ◽  
Population Pharmacokinetic ◽  
Breast Cancer Patients ◽  
Nonlinear Elimination

PURPOSE The aim of this study was to investigate the covariance between the pharmacokinetics of the three components of the FEC regimen, epirubicin (EPI), fluorouracil (5-FU), and the cyclophosphamide (CP) metabolite 4-hydroxycyclophosphamide (4-OHCP), in breast cancer patients. PATIENTS AND METHODS Data from 21 women were collected over a total of 35 cycles. 5-FU (300 to 600 mg/m2) and CP (300 to 600 mg/m2) were administered as bolus injections, whereas EPI (15 to 60 mg/m2) was administered either as a bolus injection or as an infusion. The pharmacokinetics of the component drugs were monitored using a limited sampling scheme. Population pharmacokinetic models for each of the three drugs were developed using the program NONMEM. RESULTS The data for 5-FU were best described by a one-compartment model with nonlinear elimination, where the maximal rate of elimination (Vmax) and the concentration at which the elimination was half-maximal (Km) were 105 mg/L.h and 27 mg/L, respectively. EPI concentration-time profiles showed a triexponential decline, with a mean terminal half-life of 24 hours and a clearance (CL) of 59 L/h. The elimination of 4-OHCP was monoexponential, with a mean half-life of 7 hours. The interindividual coefficients of variation (CVs) in CL were 30%, 22%, and 41% for 5-FU, EPI, and 4-OHCP, respectively. The corresponding values for intrapatient course-to-course variability in CL were 11%, 8%, and 27%. No significant correlation in any of the pharmacokinetic parameters between the drugs was found. CONCLUSION Individualization of dosing of the FEC regimen using therapeutic drug monitoring and attempts to find concentration-response relationships may be successful, but requires that the exposure of all three drugs is considered simultaneously.

Propofol Pharmacokinetics and Pharmacodynamics for Depth of Sedation in Nonventilated Infants after Major Craniofacial Surgery

2006 ◽  
Vol 104 (3) ◽  
pp. 466-474 ◽  
Author(s):  
Mariska Y. M. Peeters ◽  
Sandra A. Prins ◽  
Catherijne A. J. Knibbe ◽  
Joost DeJongh ◽  
Ron H. N. van Schaik ◽  
...  
Keyword(s):  
Bispectral Index ◽  
Coefficient Of Variation ◽  
Craniofacial Surgery ◽  
Dose Titration ◽  
Maximum Effect ◽  
Population Pharmacokinetic ◽  
Healthy Children ◽  
Pharmacokinetics And Pharmacodynamics ◽  
Emax Model ◽  
Behavior Scale

Background To support safe and effective use of propofol in nonventilated children after major surgery, a model for propofol pharmacokinetics and pharmacodynamics is described. Methods After craniofacial surgery, 22 of the 44 evaluated infants (aged 3-17 months) in the pediatric intensive care unit received propofol (2-4 mg . kg-1 . h-1) during a median of 12.5 h, based on the COMFORT-Behavior score. COMFORT-Behavior scores and Bispectral Index values were recorded simultaneously. Population pharmacokinetic and pharmacodynamic modeling was performed using NONMEM V (GloboMax LLC, Hanover, MD). Results In the two-compartment model, body weight (median, 8.9 kg) was a significant covariate. Typical values were Cl = 0.70 . (BW/8.9)0.61 l/min, Vc = 18.8 l, Q = 0.35 l/min, and Vss = 146 l. In infants who received no sedative, depth of sedation was a function of baseline, postanesthesia effect (Emax model), and circadian night rhythm. In agitated infants, depth of sedation was best described by baseline, postanesthesia effect, and propofol effect (Emax model). The propofol concentration at half maximum effect was 1.76 mg/l (coefficient of variation = 47%) for the COMFORT-Behavior scale and 3.71 mg/l (coefficient of variation = 145%) for the Bispectral Index. Conclusions Propofol clearance is two times higher in nonventilated healthy children than reported in the literature for ventilated children and adults. Based on the model, the authors advise a propofol dose of 30 mg/h in a 10-kg infant to achieve values of 12-14 on the COMFORT-Behavior scale and 70-75 on the Bispectral Index during the night. Wide pharmacodynamic variability emphasizes the importance of dose titration.

scholarly journals Population pharmacokinetics and dose optimization of vancomycin in neonates

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Soon Min Lee ◽  
Seungwon Yang ◽  
Soyoung Kang ◽  
Min Jung Chang
Keyword(s):  
Pharmacokinetic Analysis ◽  
Dose Optimization ◽  
Pharmacokinetic Parameters ◽  
Therapeutic Drug ◽  
Population Pharmacokinetic ◽  
Optimal Dosage ◽  
Mixed Effect ◽  
Final Model ◽  
Population Pharmacokinetic Modeling ◽  
First Order

AbstractThe pharmacokinetics of vancomycin vary among neonates, and we aimed to conduct population pharmacokinetic analysis to determine the optimal dosage of vancomycin in Korean neonates. From a retrospective chart review, neonates treated with vancomycin from 2008 to 2017 in a neonatal intensive care unit (NICU) were included. Vancomycin concentrations were collected based on therapeutic drug monitoring, and other patient characteristics were gathered through electronic medical records. We applied nonlinear mixed-effect modeling to build the population pharmacokinetic model. One- and two-compartment models with first-order elimination were evaluated as potential structural pharmacokinetic models. Allometric and isometric scaling was applied to standardize pharmacokinetic parameters for clearance and volume of distribution, respectively, using fixed powers (0.75 and 1, respectively, for clearance and volume). The predictive performance of the final model was developed, and dosing strategies were explored using Monte Carlo simulations with AUC0–24 targets 400–600. The patient cohort included 207 neonates, and 900 vancomycin concentrations were analyzed. Only 37.4% of the analyzed concentrations were within trough concentrations 5–15 µg/mL. A one-compartment model with first-order elimination best described the vancomycin pharmacokinetics in neonates. Postmenstrual age (PMA) and creatinine clearance (CLcr) affected the clearance of vancomycin, and model evaluation confirmed the robustness of the final model. Population pharmacokinetic modeling and dose optimization of vancomycin in Korean neonates showed that vancomycin clearance was related to PMA and CLcr, as well as body weight. A higher dosage regimen than the typical recommendation is suggested.

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