scholarly journals MR Spectroscopy Shows Long Propylene Glycol Half-Life in Neonatal Brain

Neonatology ◽  
2021 ◽  
pp. 1-9
Author(s):  
Monique van de Lagemaat ◽  
Laura A. van de Pol ◽  
Inge A. Zonnenberg ◽  
Bregje C.M. Witjes ◽  
Petra J.W. Pouwels
Keyword(s):  
Propylene Glycol ◽  
Mr Spectroscopy ◽  
Half Life ◽  
Perinatal Asphyxia ◽  
Volume Of Distribution ◽  
Neonatal Brain ◽  
First Order ◽  
Zero Order Kinetics ◽  
Short Echo Time ◽  
Clearance Model

<b><i>Introduction:</i></b> Neonatal propylene glycol (PG) clearance is low with long plasma half-life. We hypothesized that neonatal brain PG clearance is diminished and may be related to perinatal asphyxia, infection, or stroke, via different blood-brain barrier permeability. This study aimed to estimate cerebral PG half-life with a clearance model including PG measured with MR spectroscopy (MRS) in neonates that received phenobarbital as the only PG source and to evaluate whether PG clearance was related to intracerebral pathology, for example, perinatal asphyxia, infection, or stroke. <b><i>Methods:</i></b> In this retrospective cohort study, 45 neonates receiving any dose of phenobarbital underwent MRS (short echo time single-voxel MRS at 1.5 T). Cumulative phenobarbital/PG doses were calculated. MRS indications were perinatal asphyxia (<i>n</i> = 22), infection (<i>n</i> = 4), stroke (<i>n</i> = 10), metabolic disease (<i>n</i> = 4), and others (<i>n</i> = 5). <b><i>Results:</i></b> Medians (interquartile range) included gestational age 39.4 (3.1) weeks, birth weight 3,146 (1,340) g, and cumulative PG dose 700 (1,120) mg/kg. First-order kinetics with mono-exponential decay showed cerebral PG half-life of 40.7 h and volume of distribution of 1.6 L/kg. Zero-order kinetics showed a rate constant of 0.048 mM/h and a volume of distribution of 2.3 L/kg, but the fit had larger residuals than the first-order model. There were no differences in ΔPG (i.e., PG estimated with clearance model minus PG observed with MRS) in infants with perinatal asphyxia, infection, or stroke. <b><i>Discussion/Conclusion:</i></b> This study showed a long cerebral PG half-life of 40.7 h in neonates, unrelated to perinatal asphyxia, infection, or stroke. These findings should increase awareness of possible toxic PG concentrations in neonatal brain due to intravenous PG-containing drugs.

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 &lt; 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 An Updated Review on Biological Half-Life & Volume of Distribution

2018 ◽  
Vol III (I) ◽  
pp. 19-26
Author(s):  
Rana Muhammad Awais Khan ◽  
Umair-ul Hassan ◽  
Shafiq-ur Rehman ◽  
Nayab Tahir
Keyword(s):  
Half Life ◽  
Pharmacological Action ◽  
Volume Of Distribution ◽  
Zero Order ◽  
The Body ◽  
Placental Barrier ◽  
First Order ◽  
First Order Kinetics ◽  
Biological Half Life ◽  
State Concentration

Biological half-life and volume of distribution of the drug are the key parameters in understanding the pharmacokinetics of the drugs within the body as they affect all the pharmacokinetic processes including absorption, distribution, metabolism and elimination of drugs and also associated with each other, ultimately effecting the Pharmacological action of the drug on its target site. Given study elaborates the various aspects of half-life, i.e., Alpha & beta half-lives, the contribution of Zero-order and first-order kinetics in ADME and interrelation among the volume of distribution & half-life along with the distribution & redistribution of the drug within the body. Moreover, the importance of half-life & Vd and the idea of Steady-state concentration is also discussed. Various types of physiological barriers, including the blood-brain barrier, placental barrier, blood-CSF barrier, affect the distribution of drugs.

In-vitro Kinetic Hydrolysis Study of Metronidazole Derivatives with Carvacrol and Eugenol Using Validated RP-HPLC Method

2020 ◽  
Vol 16 ◽  
Author(s):  
M. Alarjah
Keyword(s):  
Half Life ◽  
Hplc Method ◽  
Hydrolysis Rate ◽  
First Order ◽  
First Order Kinetics ◽  
Rp Hplc ◽  
Pharmacokinetic Properties ◽  
Pseudo First Order ◽  
Kinetic Hydrolysis

Background: Prodrugs principle is widely used to improve the pharmacological and pharmacokinetic properties of some active drugs. Much effort was made to develop metronidazole prodrugs to enhance antibacterial activity and or to improve pharmacokinetic properties of the molecule or to lower the adverse effects of metronidazole. Objective: In this work, the pharmacokinetic properties of some of monoterpenes and eugenol pro metronidazole molecules that were developed earlier were evaluated in-vitro. The kinetic hydrolysis rate constants and half-life time estimation of the new metronidazole derivatives were calculated using the validated RP-HPLC method. Method: Chromatographic analysis was done using Zorbbax Eclipse eXtra Dense Bonding (XDB)-C18 column of dimensions (250 mm, 4.6 mm, 5 μm), at ambient column temperature. The mobile phase was a mixture of sodium dihydrogen phosphate buffer of pH 4.5 and methanol in gradient elution, at 1ml/min flow rate. The method was fully validated according to the International Council for Harmonization (ICH) guidelines. The hydrolysis process carried out in an acidic buffer pH 1.2 and in an alkaline buffer pH 7.4 in a thermostatic bath at 37ºC. Results: The results followed pseudo-first-order kinetics. All metronidazole prodrugs were stable in the acidic pH, while they were hydrolysed in the alkaline buffer within a few hours (6-8 hr). The rate constant and half-life values were calculated, and their values were found to be 0.082- 0.117 hr-1 and 5.9- 8.5 hr., respectively. Conclusion: The developed method was accurate, sensitive, and selective for the prodrugs. For most of the prodrugs, the hydrolysis followed pseudo-first-order kinetics; the method might be utilised to conduct an in-vivo study for the metronidazole derivatives with monoterpenes and eugenol.

Comparative metabolic clearance rate, volume of distribution and plasma half-life of human β-lipotropin and acth

Life Sciences ◽  
1978 ◽  
Vol 23 (23) ◽  
pp. 2323-2330 ◽  
Author(s):  
Anthony S. Liotta ◽  
Choh Hao Li ◽  
George C. Schussler ◽  
Dorothy T. Krieger
Keyword(s):  
Clearance Rate ◽  
Half Life ◽  
Volume Of Distribution ◽  
Metabolic Clearance ◽  
Metabolic Clearance Rate ◽  
Plasma Half Life

3. Half-Life and Volume of Distribution

1968 ◽  
Vol 2 (5) ◽  
pp. 126-133 ◽  
Author(s):  
John G. Wagner
Keyword(s):  
Half Life ◽  
Volume Of Distribution

scholarly journals Pharmacokinetics of Once Daily Intraperitoneal Cefazolin in Continuous Ambulatory Peritoneal Dialysis Patients

2000 ◽  
Vol 11 (6) ◽  
pp. 1117-1121
Author(s):  
CHAI LUAN LOW ◽  
KAMANI GOPALAKRISHNA ◽  
WAI CHOONG LYE
Keyword(s):  
Peritoneal Dialysis ◽  
Continuous Ambulatory Peritoneal Dialysis ◽  
Half Life ◽  
Volume Of Distribution ◽  
Hplc Method ◽  
Dialysis Patients ◽  
Suitable Alternative ◽  
Once Daily ◽  
Cefazolin Sodium ◽  
Plasma Half Life

Abstract. This study determined the pharmacokinetic characteristics of once daily intraperitoneal (IP) cefazolin in continuous ambulatory peritoneal dialysis (CAPD) patients. Each of the 10 volunteer CAPD patients without active peritonitis received a single IP dose of 1 g of cefazolin sodium for a 6-h dwell. All patients underwent a fixed CAPD regimen comprising a first 6-h dwell followed by two 3-h dwells and a final 12-h overnight dwell. Blood and dialysate samples were collected at 0, 0.5, 1, 2, 3, 6 (end of first dwell), and 24 h after the administration of IP cefazolin. Any urine produced was collected over the 24-h study period. A validated HPLC method was used to analyze cefazolin in plasma, dialysate, and urine. The bioavailability was found to be 77.9 ± 3.1%, volume of distribution 0.20 ± 0.05 L/kg, and plasma half-life 39.9 ± 25.4 h. Mean total, renal, and peritoneal clearances were 4.5 ± 2.3, 1.4 ± 1.1, and 3.5 ± 1.8 ml/min, respectively. Mean plasma and dialysate concentrations at 24 h were 42.8 ± 14.3 and 31.8 ± 11.7 mcg/ml, respectively, well above the minimum inhibitory concentrations (MIC) of susceptible organisms. A once daily IP cefazolin dose of 500 mg/L gave desirable pharmacokinetic attributes for use as a suitable alternative to vancomycin for empiric treatment of CAPD-associated peritonitis.

Observation of a radical intermediate in the one electron oxidation of 5-methyl-1-thia-5-azacyclooctane by •Br2−

1984 ◽  
Vol 62 (9) ◽  
pp. 1874-1876 ◽  
Author(s):  
Warren Kenneth Musker ◽  
Parminder S. Surdhar ◽  
Rizwan Ahmad ◽  
David A. Armstrong
Keyword(s):  
Aqueous Solution ◽  
Rate Constant ◽  
Half Life ◽  
Cation Radical ◽  
Order Rate Constant ◽  
Type Structure ◽  
Radical Intermediate ◽  
Text Type ◽  
First Order ◽  
The One

The one electron oxidant •Br2− reacts with 5-methyl-1-thia-5-azacyclooctane (4) in aqueous solution at high pH with an overall rate constant of ~2 × 108 M s−1. The radical intermediate produced has a broad maximum at 500 nm with ε = 2400 M−1 cm−1 and at pH 10 decays with a first order rate constant of 2.3 ± 0.3 × 104 s−1, first half-life of 30 ± 5 μs. Its characteristics do not correspond to those of the [Formula: see text] species reported by Asmus and co-workers. The species appears to be the same as the cation radical reported earlier in the one electron oxidation of 4 in acetonitrile. This species is considered to have an [Formula: see text] type structure, which provides transannular stabilization.

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