scholarly journals Model Informed Development of VRC01 in Newborn Infants Using a Population Pharmacokinetics Approach

2020 ◽  
Vol 109 (1) ◽  
pp. 184-192
Author(s):  
Jerry Li ◽  
Mina Nikanjam ◽  
Coleen K. Cunningham ◽  
Elizabeth J. McFarland ◽  
Emily E. Coates ◽  
...  
Keyword(s):  
Population Pharmacokinetics ◽  
Newborn Infants

scholarly journals Population Pharmacokinetics of Ciprofloxacin in Neonates and Young Infants Less than Three Months of Age

2014 ◽  
Vol 58 (11) ◽  
pp. 6572-6580 ◽  
Author(s):  
Wei Zhao ◽  
Helen Hill ◽  
Chantal Le Guellec ◽  
Tim Neal ◽  
Sarah Mahoney ◽  
...  
Keyword(s):  
Population Pharmacokinetics ◽  
Newborn Infants ◽  
Compartment Model ◽  
Population Pharmacokinetic Analysis ◽  
Pharmacokinetic Analysis ◽  
Population Pharmacokinetic ◽  
Pharmacokinetic Studies ◽  
Dosing Regimen ◽  
Creatinine Concentration ◽  
Young Infants

ABSTRACTCiprofloxacin is used in neonates with suspected or documented Gram-negative serious infections. Currently, its use is off-label partly because of lack of pharmacokinetic studies. Within the FP7 EU project TINN (Treat Infection in NeoNates), our aim was to evaluate the population pharmacokinetics of ciprofloxacin in neonates and young infants <3 months of age and define the appropriate dose in order to optimize ciprofloxacin treatment in this vulnerable population. Blood samples were collected from neonates treated with ciprofloxacin and concentrations were quantified by high-pressure liquid chromatography–mass spectrometry. Population pharmacokinetic analysis was performed using NONMEM software. The data from 60 newborn infants (postmenstrual age [PMA] range, 24.9 to 47.9 weeks) were available for population pharmacokinetic analysis. A two-compartment model with first-order elimination showed the best fit with the data. A covariate analysis identified that gestational age, postnatal age, current weight, serum creatinine concentration, and use of inotropes had a significant impact on ciprofloxacin pharmacokinetics. Monte Carlo simulation demonstrated that 90% of hypothetical newborns with a PMA of <34 weeks treated with 7.5 mg/kg twice daily and 84% of newborns with a PMA ≥34 weeks and young infants receiving 12.5 mg/kg twice daily would reach the AUC/MIC target of 125, using the standard EUCAST MIC susceptibility breakpoint of 0.5 mg/liter. The associated risks of overdose for the proposed dosing regimen were <8%. The population pharmacokinetics of ciprofloxacin was evaluated in neonates and young infants <3 months old, and a dosing regimen was established based on simulation.

Pilot evaluation of the population pharmacokinetics of bumetanide in term newborn infants with seizures

2015 ◽  
Vol 56 (3) ◽  
pp. 284-290 ◽  
Author(s):  
Vincent Jullien ◽  
Ronit M. Pressler ◽  
Geraldine Boylan ◽  
Mats Blennow ◽  
Neil Marlow ◽  
...  
Keyword(s):  
Population Pharmacokinetics ◽  
Newborn Infants ◽  
Term Newborn

Oxygen for the resuscitation of newborn infants

2016 ◽  
Vol 03 (03) ◽  
pp. 155-159
Author(s):  
Elena Cubells ◽  
María Cernada ◽  
Isabel Torres-Cuevas ◽  
Julia Kuligowski ◽  
Javier Escobar ◽  
...  
Keyword(s):  
Newborn Infants

Immunologic Studies of Antithrombin III Heparin Cofactor in the Newborn

1978 ◽  
Vol 39 (03) ◽  
pp. 624-630 ◽  
Author(s):  
W E Hathaway ◽  
L L Neumann ◽  
C A Borden ◽  
L J Jacobson
Keyword(s):  
Gestational Age ◽  
Antithrombin Iii ◽  
Newborn Infants ◽  
Term Infant ◽  
Sick Newborn ◽  
At Iii ◽  
Thrombotic Complications ◽  
Low Levels ◽  
Collection Methods ◽  
Made In

SummarySerial quantitative immunoelectrophoretic (IE) measurements of antithrombin III heparin cofactor (AT III) were made in groups of well and sick newborn infants classified by gestational age. Collection methods (venous vs. capillary) did not influence the results; serum IE measurements were comparable to AT III activity by a clotting method. AT III is gestational age-dependent, increasing from 28.7% of normal adult values at 28-32 weeks to 50.9% at 37-40 weeks, and shows a gradual increase to term infant levels (57.4%) by 3-4 weeks of age. Infants with the respiratory distress syndrome (RDS) show lower levels of AT III in the 33-36 week group, 22% vs. 44% and in the 37-40 week group, 33.6% vs. 50.9%, than prematures without RDS. Infants of 28-32 week gestational age had only slight differences, RDS = 24%, non-RDS = 28.7%. The lowest levels of AT III were seen in patients with RDS complicated by disseminated intravascular coagulation and those with necrotizing enterocolitis. Crossed IE on representative infants displayed a consistent pattern which was identical to adult controls except for appropriate decreases in the amplitude of the peaks. The thrombotic complications seen in the sick preterm infant may be related to the low levels of AT III.

The Platelet of the Newborn Infant – Adenine Nucleotide Metabolism and Release

1980 ◽  
Vol 43 (02) ◽  
pp. 099-103 ◽  
Author(s):  
J M Whaun ◽  
P Lievaart ◽  
Keyword(s):  
Newborn Infant ◽  
Adenine Nucleotide ◽  
Platelet Rich Plasma ◽  
Adenine Nucleotides ◽  
Newborn Infants ◽  
Specific Radioactivity ◽  
Nucleotide Metabolism ◽  
Breakdown Product ◽  
Term Infants ◽  
Adenine Nucleotide Metabolism

SummaryBlood from normal full term infants, mothers and normal adults was collected in citrate. Citrated platelet-rich plasma was prelabelled with 3H-adenine and reacted with release inducers, collagen and adrenaline. Adenine nucleotide metabolism, total adenine nucleotide levels and changes in sizes of these pools were determined in platelets from these three groups of subjects.At rest, the platelet of the newborn infant, compared to that of the mother and normal adult, possessed similar amounts of adenosine triphosphate (ATP), 4.6 ± 0.2 (SD), 5.0 ± 1.1, 4.9 ± 0.6 µmoles ATP/1011 platelets respectively, and adenosine diphosphate (ADP), 2.4 ± 0.7, 2.8 ± 0.6, 3.0 ± 0.3 umoles ADP/1011 platelets respectively. However the marked elevation of specific radioactivity of ADP and ATP in these resting platelets indicated the platelet of the neonate has decreased adenine nucleotide stores.In addition to these decreased stores of adenine nucleotides, infant platelets showed significantly impaired release of ADP and ATP on exposure to collagen. The release of ADP in infants, mothers, and other adults was 0.9 ± 0.5 (SD), 1.5 ± 0.5, 1.5 ± 0.1 umoles/1011 platelets respectively; that of ATP was 0.6 ± 0.3, 1.0 ± 0.1,1.3 ± 0.2 µmoles/1011 platelets respectively. With collagen-induced release, platelets of newborn infants compared to those of other subjects showed only slight increased specific radioactivities of adenine nucleotides over basal levels. The content of metabolic hypoxanthine, a breakdown product of adenine nucleotides, increased in both platelets and plasma in all subjects studied.In contrast, with adrenaline as release inducer, the platelets of the newborn infant showed no adenine nucleotide release, no change in total ATP and level of radioactive hypoxanthine, and minimal change in total ADP. The reason for this decreased adrenaline reactivity of infant platelets compared to reactivity of adult platelets is unknown.Infant platelets may have different membranes, with resulting differences in regulation of cellular processes, or alternatively, may be refractory to catecholamines because of elevated levels of circulating catecholamines in the newborn period.

Newborn Platelet Dysfunction: a Storage Pool and Release Defect

1976 ◽  
Vol 36 (01) ◽  
pp. 200-207 ◽  
Author(s):  
Donald G. Corby ◽  
Thomas F. Zuck
Keyword(s):  
Specific Activity ◽  
Platelet Rich Plasma ◽  
Adenine Nucleotides ◽  
Blood Platelets ◽  
Newborn Infants ◽  
Specific Radioactivity ◽  
High Dose ◽  
Platelet Dysfunction ◽  
Paired Samples ◽  
Normal Adults

SummaryPer cent aggregation, release and content of adenine nucleotides, and specific radioactivity were evaluated in citrated platelet-rich plasma (PRP) prepared from paired samples of maternal and cord blood. Platelets of newborn infants aggregated normally in response to high dose ADP (20 μM), strong collagen suspensions, and thrombin; however, when compared with PRP from the mothers or from normal adults, per cent aggregation in response to lower concentrations of ADP (2 μM), weak collagen, and part particularly epinephrine was markedly reduced. Nucleotide release after stimulation of the newborns’ PRP with the latter two inducers was also impaired. ATP and ADP content of the newborns’ platelets was also significantly less than that of their mothers or of normal adults, but specific activity was normal. The data suggest that the impairment of ADP release in the platelets of newborn infants is due to decreased sensitivity to external stimuli. Since metabolic ATP is necessary for the platelet release reaction, it is postulated that the platelet dysfunction results from a lack of metabolic ATP.

Oxygen Consumption in Platelets of Newborn Infants before and after Stimulation by Thrombin.

1976 ◽  
Vol 35 (03) ◽  
pp. 712-716 ◽  
Author(s):  
D. Del Principe ◽  
G Mancuso ◽  
A Menichelli ◽  
G Maretto ◽  
G Sabetta
Keyword(s):  
Oxygen Consumption ◽  
Cord Blood ◽  
Umbilical Cord ◽  
Newborn Infant ◽  
Umbilical Cord Blood ◽  
Newborn Infants ◽  
O2 Consumption ◽  
Adult Control ◽  
Healthy Newborn ◽  
Before And After

SummaryThe authors compared the oxygen consumption in platelets from the umbilical cord blood of 36 healthy newborn infants with that of 27 adult subjects, before and after thrombin addition (1.67 U/ml). Oxygen consumption at rest was 6 mμmol/109/min in adult control platelets and 5.26 in newborn infants. The burst in oxygen consumption after thrombin addition was 26.30 mμmol/109/min in adults and 24.90 in infants. Dinitrophenol did not inhibit the burst of O2 consumption in platelets in 8 out of 10 newborn infants, while the same concentration caused a decrease in 9 out of 10 adult subjects. Deoxyglucose inhibited the burst in O2 consumption in newborn infant and adult platelets by about 50%. KCN at the concentration of 10−4 M completely inhibited basal oxygen consumption but did not completely inhibit the burst after thrombin. At the concentration of 10−3 M, it inhibited both basal O2 consumption and the burst in infants and adult subjects.

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