scholarly journals Pharmacokinetics of Penicillin G in Infants with a Gestational Age of Less than 32 Weeks

2007 ◽  
Vol 51 (10) ◽  
pp. 3720-3725 ◽  
Author(s):  
Anouk E. Muller ◽  
Joost DeJongh ◽  
Ymka Bult ◽  
Wil H. F. Goessens ◽  
Johan W. Mouton ◽  
...  
Keyword(s):  
Gestational Age ◽  
Volume Of Distribution ◽  
Penicillin G ◽  
Preterm Neonates ◽  
Population Estimates ◽  
Mixed Effects Modeling ◽  
Central Volume ◽  
Total Body ◽  
Intercompartmental Clearance ◽  
Susceptibility Breakpoint

ABSTRACT The pharmacokinetics of penicillin G were studied in 20 preterm neonates with a gestational age of less than 32 weeks on day 3 of life by using a population approach performed with the nonlinear mixed effects modeling program NONMEM. The derived population estimates and the correlation matrix of these estimates were used to perform Monte Carlo simulations and obtain the probability of target attainment (PTA). The pharmacokinetics of penicillin G were best described by a two-compartment pharmacokinetic model. The population estimates of the central volume of distribution, the peripheral volume of distribution, the intercompartmental clearance, and the total body clearance were 0.359 ± 0.06 liter, 0.152 ± 0.03 liter, 0.774 ± 0.28 liter/h, and 0.103 ± 0.01 liter/h (mean ± standard error), respectively. The terminal half-life was 3.9 h. Clearance increased significantly with increasing birth weight. Assuming the percentage of time that the concentration of unbound drug remained above the MIC of 50% for preterm neonates, the susceptibility breakpoint based on a 100% PTA was ≤4 mg/liter, simulating the current dosing regimen of 50,000 U/kg every 12 h. This regimen is therefore adequate for the treatment of common infections in neonates on the third day of life.

scholarly journals Rapidly maturing fentanyl clearance in preterm neonates

2019 ◽  
Vol 104 (6) ◽  
pp. F598-F603 ◽  
Author(s):  
Swantje Völler ◽  
Robert B Flint ◽  
Peter Andriessen ◽  
Karel Allegaert ◽  
Luc J I Zimmermann ◽  
...  
Keyword(s):  
Gestational Age ◽  
Compartment Model ◽  
Volume Of Distribution ◽  
Preterm Neonates ◽  
Population Pharmacokinetic ◽  
Additional Information ◽  
Two Compartment Model ◽  
Require Dose ◽  
Preterm Newborns ◽  
Pharmacodynamic Data

BackgroundFentanyl is frequently used off-label in preterm newborns. Due to very limited pharmacokinetic and pharmacodynamic data, fentanyl dosing is mostly based on bodyweight. This study describes the maturation of the pharmacokinetics in preterm neonates born before 32 weeks of gestation.Methods442 plasma samples from 98 preterm neonates (median gestational age: 26.9 (range 23.9–31.9) weeks, postnatal age: 3 (range 0–68) days, bodyweight 1.00 (range 0.39–2.37) kg) were collected in an opportunistic trial and fentanyl plasma levels were determined. NONMEM V.7.3 was used to develop a population pharmacokinetic model and to perform simulations.ResultsFentanyl pharmacokinetics was best described by a two-compartment model. A pronounced non-linear influence of postnatal and gestational age on clearance was identified. Clearance (L/hour/kg) increased threefold, 1.3-fold and 1.01-fold in the first, second and third weeks of life, respectively. In addition, clearance (L/hour/kg) was 1.4-fold and 1.7-fold higher in case of a gestational age of 28 and 31 weeks, respectively, compared with 25 weeks. Volume of distribution changed linearly with bodyweight and was 8.7 L/kg. To achieve similar exposure across the entire population, a continuous infusion (µg/kg/hour) dose should be reduced by 50% and 25% in preterm neonates with a postnatal age of 0–4 days and 5–9 days in comparison to 10 days and older.ConclusionBecause of low clearance, bodyweight-based dosages may result in fentanyl accumulation in neonates with the lowest postnatal and gestational ages which may require dose reduction. Together with additional information on the pharmacodynamics, the results of this study can be used to guide dosing.

Acute kidney injury in preterm neonates with ≤30 weeks of gestational age and its risk factors

2019 ◽  
Vol 71 (5) ◽  
Author(s):  
Rita Ladeiras ◽  
Filipa Flor-De-Lima ◽  
Henrique Soares ◽  
Bárbara Oliveira ◽  
Hercília Guimarães
Keyword(s):  
Risk Factors ◽  
Acute Kidney Injury ◽  
Gestational Age ◽  
Kidney Injury ◽  
Preterm Neonates

scholarly journals Comparable Population Pharmacokinetics and Pharmacodynamic Breakpoints of Cefpirome in Cystic Fibrosis Patients and Healthy Volunteers

2011 ◽  
Vol 55 (6) ◽  
pp. 2927-2936 ◽  
Author(s):  
J. B. Bulitta ◽  
M. Kinzig ◽  
C. B. Landersdorfer ◽  
U. Holzgrabe ◽  
U. Stephan ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Healthy Volunteers ◽  
High Performance ◽  
Standard Dose ◽  
Total Body Weight ◽  
Volume Of Distribution ◽  
Nonparametric Bootstrap ◽  
Population Pk ◽  
Total Body ◽  
Similar Body

ABSTRACTCystic fibrosis (CF) patients are often reported to have higher clearances and larger volumes of distribution per kilogram of total body weight (WT) for beta-lactams than healthy volunteers. As pharmacokinetic (PK) data on cefpirome from studies of CF patients are lacking, we systematically compared its population PK and pharmacodynamic breakpoints for CF patients and healthy volunteers of similar body size. Twelve adult CF patients (median lean body mass [LBM] = 45.7 kg) and 12 healthy volunteers (LBM = 50.0 kg) received a single 10-min intravenous infusion of 2 g cefpirome. Plasma and urine concentrations were determined by high-performance liquid chromatography (HPLC). Population PK and Monte Carlo simulations were performed using NONMEM and S-ADAPT and a duration of an unbound plasma concentration above the MIC ≥ 65% of the dosing interval as a pharmacodynamic target. Unscaled clearances for CF patients were similar to those seen with healthy volunteers, and the volume of distribution was 6% lower for CF patients. Linear scaling of total clearance by WT resulted in clearance that was 20% higher (P≤ 0.001 [nonparametric bootstrap]) in CF patients. Allometric scaling by LBM explained the differences between the two subject groups with respect to average clearance and volume of distribution and reduced the unexplained between-subject variability of renal and nonrenal clearance by 10 to 14%. For the CF patients, robust (>90%) probabilities of target attainment (PTA) were achieved by the administration of a standard dose of 2 g/70 kg WT every 12 h (Q12h) given as 30-min infusions for MICs ≤ 1.5 mg/liter. As alternative dosage regimens, a 5-h infusion of 1.33 g/70 kg WT Q8h achieved robust PTAs for MICs ≤ 8 to 12 mg/liter and a continuous infusion of 4 g/day for MICs ≤ 12 mg/liter. Prolonged infusion of cefpirome is expected to be superior to short-term infusions for MICs between 2 and 12 mg/liter.

scholarly journals Intestinal Permeability in Preterm Neonates is not Related to Gestational Age or Birth Weight. 75

1996 ◽  
Vol 40 (3) ◽  
pp. 527-527
Author(s):  
Ruurd M van Elburg ◽  
Femke M van Overbeek ◽  
Carin M Bunkers ◽  
Willem PF Fetter ◽  
Sidarto Bambang Oetomo ◽  
...  
Keyword(s):  
Birth Weight ◽  
Intestinal Permeability ◽  
Gestational Age ◽  
Preterm Neonates

Comparison of Prophylaxis and Rescue Treatment With Curosurf in Neonates Less than 30 Weeks' Gestation: A Randomized Trial

PEDIATRICS ◽  
1993 ◽  
Vol 92 (6) ◽  
pp. 768-774 ◽  
Author(s):  
Johannes Egberts ◽  
J. Peter de Winter ◽  
Gunnar Sedin ◽  
Martin J.K. de Kleine ◽  
Ulf Broberger ◽  
...  
Keyword(s):  
Mechanical Ventilation ◽  
Gestational Age ◽  
Periventricular Leukomalacia ◽  
Ductus Arteriosus ◽  
Expectant Management ◽  
Supplemental Oxygen ◽  
Preterm Neonates ◽  
Transcutaneous Oxygen ◽  
Prophylaxis Group ◽  
Rescue Treatment

Objective. The aim of this randomized clinical trial was to evaluate the immediate effects of prophylactic administration of Curosurf and to compare outcomes after prophylactic or expectant management. Study design. Porcine surfactant (Curosurf, 200 mg/kg body weight) was administered intratracheally within 10 minutes of birth to preterm neonates with a gestational age of 26 to 29 weeks (n = 75); rescue-eligible neonates (n = 72) were initially subjected to a sham maneuver. The primary end points of the trial, evaluated at the age of 6 hours, were to obtain (1) a 40% decrease in the ratio between transcutaneous oxygen tension (tcPo2) (kPa) and fraction of inspired oxygen (Fio2), and (2) a 50% decrease in the incidence of radiologically verified respiratory distress syndrome (RDS). After 6 to 24 hours, a similar dose of surfactant was given to the neonates of both the prophylaxis and the rescue-eligible group, if they needed mechanical ventilation with an Fio2 ≥ 0.6. Results. At 6 hours the prophylaxis group had, in comparison with the rescue-eligible group, significantly higher tcPo2/Fio2 ratios (mean ± SD: 39.7 ± 15.3 vs 28.1 ± 18.1; P < .001) and less severe RDS by radiological scoring (χ2 = 14.9; P = .005). Severe RDS was present in 19% of the prophylactically treated neonates versus 32% in the rescue-eligible group (P < .05). The prophylaxis group needed shorter periods of Fio2 > 0.40 than the rescueeligible neonates (P < .01), and eight neonates of the prophylaxis group (11%) versus 23 of the rescue-eligible group (32%) qualified for rescue treatment with surfactant in the interval 6 to 24 hours (P < .01). There were no differences in the incidence or severity of pneumothorax, pulmonary interstitial emphysema, cerebral hemorrhage, periventricular leukomalacia, patent ductus arteriosus, in the duration of mechanical ventilation or time in supplemental oxygen, or in mortality. Conclusions. Subgroup analysis revealed (1) that administration of corticosteroids reduced the risk of developing neonatal RDS as effectively as did surfactant prophylaxis at birth, and (2) that prophylaxis was effective especially in neonates with gestational age <28 weeks or birth weight <1000 g, in male neonates, and in neonates who had received no antenatal treatment with corticosteriods. Our data indicate that prophylactic treatment with surfactant should be considered in high-risk neonates fulfilling these latter criteria.

Oral acetaminophen administration for patent ductus arteriosus (PDA) closure in preterm neonates

2021 ◽  
Vol 43 (3) ◽  
pp. 254-259
Author(s):  
Mahmood Samadi ◽  
Zahra Nabaee ◽  
Manizheh Mostafagharebaghi ◽  
Majid Mahalei ◽  
Elham Sheykhsaran ◽  
...  
Keyword(s):  
Patent Ductus Arteriosus ◽  
Gestational Age ◽  
Statistical Significance ◽  
Ductus Arteriosus ◽  
Preterm Neonates ◽  
Term Infants ◽  
Treatment Data ◽  
Kolmogorov Smirnov ◽  
Study Population ◽  
Patent Ductus

Background: Patent Ductus Arteriosus (PDA) is considered one of the most prevalent types of congenital heart disease. The closure of the ductus arteriosus physiologically occurs at the first 48-72 hours after the birth in healthy term infants. Different causes can result in the pathological opening of ductus arteriosus. This study aims to investigate the effect of oral acetaminophen on the closure of PDA in preterm neonates. Methods: The present study is a trial without control. Forty-five preterm neonates with a gestational age of <32 weeks were studied. Acetaminophen was orally administered with a dose of 10mg/kg every 6 hours for three days. Closure of ductus arteriosus was considered as the success of treatment. Data were analyzed using SPSS 15. Data were reported as )frequency-percent) and mean ± SD. To evaluate the normal distribution of data, we used a Kolmogorov-Smirnov test. Statistical significance was defined as P<0.05. Results: The study population consisted of 20 male and 25 female infants with the mean gestational age of 28.95 ± 1.66 weeks. Cesarean-born infants and vaginal-born infants consisted 17.8% and 82.2% of the study population, respectively. The proportion of PDA closure after administration of oralacetaminophen was 82.3%. Conclusion: The current study indicates that oral acetaminophen is highly effective in closing PDA. Considering its trivial side effects, it has the potency to be a convenient option for treating this condition.

Preterm Pulmonary Hemorrhage Is Associated with Multiple Births but Not with Intracytoplasmic Sperm Injection: A Cohort Study on Medical Records

2018 ◽  
Vol 35 (11) ◽  
pp. 1087-1092
Author(s):  
Stefanie Stierling ◽  
Ralf-Dieter Hilgers ◽  
Sonja Trepels-Kottek ◽  
Konrad Heimann ◽  
Thorsten Orlikowsky ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cohort Study ◽  
Gestational Age ◽  
Intracytoplasmic Sperm Injection ◽  
Medical Records ◽  
Ductus Arteriosus ◽  
Pulmonary Hemorrhage ◽  
Multiple Births ◽  
Preterm Neonates ◽  
Increased Risk

Objective Pulmonary hemorrhage (PH) is a severe complication in preterm neonates. This study aims to identify risk factors and comorbidities of PH. Study Design A single-center cohort study on medical records including all preterm neonates of <30 weeks' gestational age was conducted in the neonatal intensive care unit of Universitätsklinikum Aachen, Germany. The occurrence of PH served as a primary end point. Gestational age, birthweight, sex, multiple births, intracytoplasmic sperm injection (ICSI), intubation, surfactant, antenatal steroids, intraventricular hemorrhage (IVH), amniotic infection syndrome, and persistent ductus arteriosus were studied as risk factors. Results In this study, 344 preterm neonates were included, of whom 36 suffered from PH (10.5%). The mean time of the first occurrence was the third day of life (standard deviation [SD]: 1.2). On average, the patients suffered from 1.5 incidents (SD: 0.8) of PH, of whom 50% were severe. Preterm neonates born as multiples (95% confidence interval [CI]: 3.1, 26.9) and those who suffered from IVH (95% CI: 2.7, 18.9) had a significantly increased risk of PH. ICSI was not an independent risk factor. Conclusion PH is significantly associated with IVH and multiple births but not with ICSI. The identification of patients at risk allows to apply prophylactic strategies of ventilation and pharmacological treatment.

Intestinal Blood Flow by Doppler Ultrasound: The Impact of Gestational Age and Time from First Enteral Feeding in Preterm Neonates

2013 ◽  
Vol 31 (04) ◽  
pp. 261-268 ◽  
Author(s):  
Cicero Silva ◽  
A. Gork ◽  
Dan Wang ◽  
Richard Ehrenkranz ◽  
Alecia Thompson
Keyword(s):  
Blood Flow ◽  
Doppler Ultrasound ◽  
Enteral Feeding ◽  
Gestational Age ◽  
Intestinal Blood Flow ◽  
Preterm Neonates ◽  
The Impact

scholarly journals Pharmacokinetics of Intravenous Piperacillin Administration in Patients Undergoing On-Line Hemodiafiltration

2009 ◽  
Vol 53 (8) ◽  
pp. 3266-3268 ◽  
Author(s):  
Kook-Hwan Oh ◽  
Chiweon Kim ◽  
Hankyu Lee ◽  
Hajeong Lee ◽  
Ji Yong Jung ◽  
...  
Keyword(s):  
Standard Deviation ◽  
Total Body Clearance ◽  
Volume Of Distribution ◽  
Pharmacokinetic Parameters ◽  
Recovery Method ◽  
Elimination Half ◽  
On Line ◽  
The Mean ◽  
Total Body ◽  
Body Clearance

ABSTRACT The pharmacokinetic characteristics of piperacillin sodium were studied in five volunteers undergoing on-line hemodiafiltration (HDF). The subjects were given 2 g of piperacillin sodium intravenously over 1 min and placed on on-line HDF for 4 h starting at 60 min after the piperacillin infusion. Noncompartmental models were employed for estimation of the pharmacokinetic parameters, and intradialytic piperacillin clearance was calculated by the recovery method. The mean volume of distribution and the elimination half-life were 0.27 ± 0.13 liter/kg (mean ± standard deviation) and 1.1 ± 0.6 h, respectively. The total body clearance of piperacillin was 0.19 ± 0.08 liter/h/kg. Piperacillin clearance through on-line HDF was 0.11 ± 0.06 liter/h/kg. The mean serum piperacillin concentration was 4.0 ± 1.9 μg/ml at the end of the 4-h on-line HDF session. The concentration of infused piperacillin recovered in the dialysate was 527 ± 236 mg (26.3% ± 11.8%). We suggest the replacement of 500 mg of piperacillin after each on-line HDF session.

scholarly journals Confounders for Neonatal Intensive Care Unit Admission ın Neonates of Mothers with Preeclampsia

2018 ◽  
Vol 24 (3) ◽  
pp. 162
Author(s):  
Cetin Kilicci ◽  
Cigdem Yayla Abide ◽  
Enis Ozkaya ◽  
Evrim Bostancı Ergen ◽  
İlter Yenidede ◽  
...  
Keyword(s):  
Intensive Care Unit ◽  
Intensive Care ◽  
Birth Weight ◽  
Intensive Care Unit Admission ◽  
Neonatal Intensive Care Unit ◽  
Gestational Age ◽  
Neonatal Intensive Care ◽  
Preterm Neonates ◽  
Apgar Scores ◽  
Gestational Age At Delivery

<p><strong>Objective:</strong> The aim of this study was to investigate the effect of some maternal and neonatal clinical parameters on the neonatal intensive care unit admission rates of neonates born to mothers who had preeclampsia. </p><p><strong>Study Design:</strong> Study included 402 singleton pregnant women with preeclampsia who admitted to Maternal-Fetal Medicine Unit of Zeynep Kamil Children and Women’s Health Training and Research Hospital. Pregnancies with uterine rupture, chorioamnionitis and congenital malformations were excluded. Some maternal and neonatal clinical characteristics were assessed to predict neonatal intensive care unit admission.</p><p><strong>Results:</strong> Among 402 neonates, 140 (35%) of them had an indication for neonatal intensive care unit admission, among 140 neonates, 136 (97%) of them were preterm neonates. Comparison of groups with and without neonatal intensive care unit admission indicated significant differences between groups in terms of gestational age, Apgar scores at 1st and 5th minutes, birth weight, some maternal laboratory parameters (Hemoglobin, hematocrit, alanine aminotransferase, aspartate aminotransferase, albumin). In multivariate analysis, among all study population, gestational age at delivery, birth weight and Apgar scores were found to be significantly associated with neonatal intensive care unit admission. On the other hand, in subgroup of term neonates, none of the variables was shown to be associated with neonatal intensive care unit admission.</p><p><strong>Conclusion:</strong> Gestational age at delivery and the birth weight are the main risk factors for neonatal intensive care unit admission of neonates born to mothers who had preeclampsia.</p>

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