scholarly journals O09 Drug delivery kinetics of intravenous gentamicin in a population of neonates

2019 ◽  
Vol 104 (6) ◽  
pp. e4.2-e4
Author(s):  
G Salis ◽  
N Medlicott ◽  
D Reith
Keyword(s):  
Drug Delivery ◽  
Time Lag ◽  
Medical Science ◽  
Compartment Model ◽  
Pharmacokinetic Parameters ◽  
List Type ◽  
First Order ◽  
Model Drug ◽  
The Individual ◽  
Kinetics Of

BackgroundGentamicin is commonly used in the NICU setting and is often administered via long lines, which increases variability in the rate of administration. We aimed to model drug delivery pharmacokinetic parameters for intravenous gentamicin administered via umbilical venous catheters (UVCs).MethodsData was modelled from infusion simulations of gentamicin delivery using UVCs with a background flow rate of 0.5 ml/h.1 Different combinations of dose (2 mg, 5 mg) were given by bolus injection over 3–5 minutes, followed by a normal saline flush (1 ml, 2 ml). Gentamicin levels were measured at 5 minute intervals over an hour via high pressure liquid chromatography.Phoenix Certara (version 8.1) was used for modelling. An extravascular model with clearance removed was used to predict parameters: absorption constant (Ka), time lag (Tlag), and bioavailability (F). F was used to enable an estimate of the variability in dose administered. Different error models were tested to ascertain which best described the data.ResultsAn extravascular one compartment model with first order absorption and additive error best described the data. Estimates for the model with a 2 mg dose and 1 ml flush were Ka 0.34L/min, Tlag 1.28min, F 0.97, standard deviation (stdev) 0.14. For 2 mg, 2 ml flush, estimates were Ka 0.86L/min, Tlag 3.01min, F 0.87, stdev 0.01. For 5 mg, 1 ml flush, estimates were Ka 0.48L/min, Tlag 3.13min, F 1.03, stdev 0.12. For 5 mg, 2 ml flush, estimates were Ka 0.83L/min, Tlag 3.29min, F 1.09, stdev 0.02. For each model epsshrinkage and nshrinkage for Tlag and F were low, however nshrinkage for ka was 0.9999.ConclusionThis is the first known modelling of gentamicin delivery kinetics. The studies all had high nshrinkage for Ka, therefore the individual estimates of ka may be unreliable. Further studies with a higher number of replicates would provide more favourable data for estimating Ka.ReferenceLala AC ( 2016). Variability in neonatal gentamicin administration influencing drug delivery kinetics (Thesis, Master of Medical Science). University of Otago.Disclosure(s)No conflict of interest declared. Funding for research via the Freemasons Society of New Zealand.

Pharmacokinetics and Tissue Residues of Sulfathiazole and Sulfamethazine in Pigs

1994 ◽  
Vol 57 (9) ◽  
pp. 796-801 ◽  
Author(s):  
LIEVE S. G. VAN POUCKE ◽  
CARLOS H. VAN PETEGHEM
Keyword(s):  
Intravenous Injection ◽  
Half Life ◽  
Intramuscular Injection ◽  
Compartment Model ◽  
Absolute Bioavailability ◽  
Pharmacokinetic Parameters ◽  
Tissue Concentrations ◽  
Single Intravenous Injection ◽  
The Individual ◽  
Residue Study

The plasma pharmacokinetics and tissue penetration of sulfathiazole (ST) and sulfamethazine (SM) after intravenous and intramuscular injection in pigs were studied. Following a single intravenous dose of 40 mg ST/kg of bodyweight or 80 mg SM/kg of bodyweight, the plasma ST and SM concentrations were best fitted to a two-compartment model. The areas under the curve were 447 ± 39 and 1485 ± 41 mg/h/L, clearances were 0.090 ± 0.007 and 0.054 ± 0.001 L/kg/h, volumes of distribution were 1.16 ± 0.16 and 0.77 ± 0.06 L/kg, half-lifes in distribution phase were l.18 ± 0.57 and 0.23 ± 0.16 h and half-lifes in eliminations phase were 9.0 ± l.6 and 9.8 ± 0.6 h. When the two compounds were administered simultaneously as a single intravenous injection, the pharmacokinetic parameters for ST were not significantly different. The values for SM show statistical differences for some important parameters: α, β and the AUC0–>∞ were significantly decreased and t1/2α, Vd and CIB were significantly increased. It can be concluded that after a single intravenous injection of 40 mg/kg, sulfathiazole has a high tl/2β resulting in higher tissue concentrations. This half-life, which is higher than what is reported in the literature, is not influenced by the simultaneous presence of sulfamethazine. The tl/2β for sulfamethazine after a single intravenous injection of 80 mg/kg is comparable to the data from the literature and is not influenced by the presence of sulfathiazole. Sulfathiazole and SM were also administered simultaneously as an intramuscular injection to healthy pigs at a dosage of 40 and 80 mg/kg bodyweight. Pharmacokinetic experiments were conducted on three pigs. From this pharmacokinetic study it can be concluded that upon a single intramuscular administration of 40 mg/kg of ST and 80 mg/kg of SM the absolute bioavailability in pigs is 0.92 ± 0.04 for ST and l.01 ± 0.07 for SM. Six pigs received five intramuscular im) injections as a single dose of ST and SM every 24 h for five consecutive days for the residue study. The pigs were slaughtered at different times after the last dose was given and samples were taken from various tissues and organs. Concentrations were determined by a microbiological method and a HPTLC method. No edible tissue contained more than 100 μg/kg of the individual sulfonamides after 10 days of withdrawal. It means that adult animals which have a shorter half-life and thus lower tissue concentrations will certainly meet the economic community EC) maximum residue limits after a 10 days withdrawal period.

Kinetics of the hydrogen/oxygen reaction II. The explosion region in salt- and alkali-coated vessels

1952 ◽  
Vol 211 (1104) ◽  
pp. 86-95 ◽  
Keyword(s):  
Mixture Composition ◽  
Spontaneous Ignition ◽  
Vessel Size ◽  
First Order ◽  
Wide Range ◽  
Chain Theory ◽  
A Chain ◽  
The Individual ◽  
Kinetics Of ◽  
Oxygen Reaction

The first, second and third explosion limits for the hydrogen/oxygen reaction have been examined over a wide range of temperature, mixture composition, vessel size and wall coating. An expression has been derived from general chain theory which can account for the observed features of the complete explosion region. It includes and relates previously given expressions for the individual limits. The reactions found to be necessary and apparently sufficient to account for the hydrogen/oxygen spontaneous ignition peninsula are those of chain destruction in triple collisions, destruction at the wall of three different chain carriers, first-order branching, second-order branching, the regeneration of ‘dead’ chains and a chain-initiating process.

scholarly journals Comparative Study of Antihypertensive Drugs Amlodipine Besylate /Metoprolol Succinate and Nebivolol Hydrochloride /Valsartan Combinations in Bilayer Tablets

2019 ◽  
Vol 9 (4-s) ◽  
pp. 529-539
Author(s):  
Selvi - Arunkumar ◽  
L. Srinivas ◽  
D. Satyavati ◽  
C. Emmanuel
Keyword(s):  
Drug Delivery ◽  
Drug Delivery System ◽  
Delivery System ◽  
Antihypertensive Drugs ◽  
Pharmacokinetic Parameters ◽  
Test Drug ◽  
Amlodipine Besylate ◽  
Metoprolol Succinate ◽  
Nebivolol Hydrochloride ◽  
Model Drug

The present research is an approach to develop a formulation platform that shall help in minimizing the time and effort taken to develop a drug delivery system. Taking bilayer tablet technology as a representation for drug delivery system, well accepted antihypertensive drugs, Amlodipine besylate and Metoprolol succinate were considered as model drugs for the study. Initially the process variables like concentration of the disintegrants, Sodium starch Glycolate and cross carmellose sodium, Polymers HPMC K100M and K4M were standardized with these drugs so that the incorporation of a new combination drugs would provide predictable results with a minimal trial runs. Nebivolol hydrochloride and Valsartan were considered as test drugs since they are novel antihypertensive drug combination and their physicochemical and pharmacokinetic parameters were almost similar to that of the model drugs. The r value 0.98943 indicates a good correlation between the release profile of Amlodipine besylate (model drug) and Nebivolol hydrochloride (test drug) from the IR layer. Similarly, the r value in the range of 0.9998 indicates a good correlation between the release profile of Metoprolol succinate (model drug) and Valsartan (test drug) from the SR layer. The comparable experimental results of the model drugs and test drugs considered for this study infer that if two drugs are similar in their physicochemical and pharmacokinetic parameters, their behavior with respect to in vitro parameters will be similar provided formulation variables remains constant. This concept could be productive in developing drug delivery system for new drugs for which extensive research and time are major constraints. Keywords: Bilayer tablets, fixed unit dosage form, Amlodipine besylate, Metoprolol Succinate Nebivolol hydrochloride, Valsartan.

scholarly journals Particle Forming Amorphous Solid Dispersions: A Mechanistic Randomized Pharmacokinetic Study in Humans

Pharmaceutics ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 401
Author(s):  
Andreas Schittny ◽  
Samuel Waldner ◽  
Urs Duthaler ◽  
Alexander Vorobyev ◽  
Rimma Abramovich ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Solid Dispersions ◽  
Amorphous Solid ◽  
Aqueous Solubility ◽  
Ambulatory Setting ◽  
Pharmacokinetic Parameters ◽  
Supersaturated Solution ◽  
Open Label ◽  
Amorphous Solid Dispersions ◽  
Model Drug

Amorphous solid dispersions (ASDs) are a promising drug-delivery strategy to overcome poor solubility through formulation. Currently, the understanding of drug absorption mechanisms from ASDs in humans is incomplete. Aiming to gain insights in this matter, we conducted a randomized cross-over design open-label clinical study (NCT03886766) with 16 healthy male volunteers in an ambulatory setting, using micro-dosed efavirenz as a model drug. In three phases, subjects were administered (1) solid ASD of efavirenz 50 mg or (2) dissolved ASD of efavirenz 50 mg or (3) a molecular solution of efavirenz 3 mg (non-ASD) as a control in block-randomized order. Endpoints were the pharmacokinetic profiles (efavirenz plasma concentration vs. time curves) and derived pharmacokinetic parameters thereof (AUC0–t, Cmax, tmax, and ka). Results showed that the dissolved ASD (intervention 2) exhibited properties of a supersaturated solution (compared to aqueous solubility) with rapid and complete absorption of the drug from the drug-rich particles. All interventions showed similar AUC0–t and were well tolerated by subjects. The findings highlight the potential of particle forming ASDs as an advanced drug-delivery system for poorly soluble drugs and provide essential insights into underlying mechanisms of ASD functioning in humans, partially validating current conceptual models.

scholarly journals Population Pharmacokinetics and Pharmacodynamic Considerations of Amodiaquine and Desethylamodiaquine in Kenyan Adults with Uncomplicated Malaria Receiving Artesunate-Amodiaquine Combination Therapy

2010 ◽  
Vol 54 (6) ◽  
pp. 2611-2617 ◽  
Author(s):  
Vincent Jullien ◽  
Bernhards Ogutu ◽  
Elizabeth Juma ◽  
Gwenaelle Carn ◽  
Charles Obonyo ◽  
...  
Keyword(s):  
Uncomplicated Malaria ◽  
Elimination Rate ◽  
Parasite Clearance ◽  
Compartment Model ◽  
Fixed Dose Combination ◽  
Fixed Dose ◽  
Pharmacokinetic Parameters ◽  
First Order ◽  
Dose Combination ◽  
The Mean

ABSTRACT Amodiaquine (AQ) is an antimalarial drug that was frequently combined with artesunate (AS) for the treatment of uncomplicated malaria due to Plasmodium falciparum and is now available as a fixed-dose combination. Despite its widespread use, the simultaneous pharmacokinetics in patients of AQ and its active metabolite, desethylamodiaquine (DAQ), were not characterized to date. The pharmacokinetics of AQ and DAQ in 54 adult patients receiving the AS/AQ combination were therefore investigated by the use of a population approach. AQ followed a 1-compartment model with first-order absorption and elimination, as well as a first-order and irreversible transformation into DAQ, which in turn followed a 2-compartment model with first-order elimination from its central compartment. The mean AQ apparent clearance and distribution volume were 3,410 liters/h and 39,200 liters, respectively. The mean terminal elimination half-life of DAQ was 211 h. Body weight was found to explain the interindividual variability of the apparent volume of distribution of AQ and the elimination rate constant of DAQ. A new dosage form consisting of a fixed-dose combination of AS and AQ was found to have no effect on the pharmacokinetic parameters of AQ and DAQ. All patients achieved parasite clearance within 4 days following the initiation of the treatment, which prevented investigation of the possible relationship between DAQ exposure and treatment outcome. This study provided the first simultaneous pharmacokinetic model for AQ and DAQ.

Kinetics of the sonophotocatalytic degradation of orange G in presence of Fe3 +

2009 ◽  
Vol 60 (8) ◽  
pp. 2195-2202 ◽  
Author(s):  
Jagannathan Madhavan ◽  
Franz Grieser ◽  
Muthupandian Ashokkumar
Keyword(s):  
Aqueous Solution ◽  
Synergetic Effect ◽  
Ultrasound Irradiation ◽  
Hybrid Technique ◽  
Comparison Study ◽  
First Order ◽  
Synergistic Enhancement ◽  
Orange G ◽  
The Individual ◽  
Kinetics Of

The degradation and mineralization of orange G (OG) in aqueous solution by means of ultrasound irradiation at a frequency of 213 kHz and its combination with Fe3 +  were investigated. The effect of Fe3 +  concentration on the degradation efficiency was studied. The degradation of the dye followed first-order like kinetics under the conditions examined. A comparison study on the hybrid technique of sonophotocatalytic degradation in the presence of Fe3 +  (SonoFenton) with the individual techniques of photocatalysis and sonolysis was also performed. A slight synergistic enhancement in the degradation of the dye was observed during the sonophotocatalytic oxidation of OG using Fe3 + . The total organic carbon (TOC) measurements, carried out in order to evaluate the mineralization efficiency of OG using sonolysis, photocatalysis and sonophotocatalysis, showed a synergetic effect of combining sonolysis and photolysis.

Influence of stable iodine on the uptake of the thyroid – model vs. experiment

2001 ◽  
Vol 40 (01) ◽  
pp. 31-37 ◽  
Author(s):  
U. Wellner ◽  
E. Voth ◽  
H. Schicha ◽  
K. Weber
Keyword(s):  
Time Course ◽  
Compartment Model ◽  
The Body ◽  
Iodine Uptake ◽  
Model Calculations ◽  
Physiological Conditions ◽  
Iodine Supply ◽  
Predicted Values ◽  
The Individual ◽  
Stable Iodine

Summary Aim: The influence of physiological and pharmacological amounts of iodine on the uptake of radioiodine in the thyroid was examined in a 4-compartment model. This model allows equations to be derived describing the distribution of tracer iodine as a function of time. The aim of the study was to compare the predictions of the model with experimental data. Methods: Five euthyroid persons received stable iodine (200 μg, 10 mg). 1-123-uptake into the thyroid was measured with the Nal (Tl)-detector of a body counter under physiological conditions and after application of each dose of additional iodine. Actual measurements and predicted values were compared, taking into account the individual iodine supply as estimated from the thyroid uptake under physiological conditions and data from the literature. Results: Thyroid iodine uptake decreased from 80% under physiological conditions to 50% in individuals with very low iodine supply (15 μg/d) (n = 2). The uptake calculated from the model was 36%. Iodine uptake into the thyroid did not decrease in individuals with typical iodine supply, i.e. for Cologne 65-85 μg/d (n = 3). After application of 10 mg of stable iodine, uptake into the thyroid decreased in all individuals to about 5%, in accordance with the model calculations. Conclusion: Comparison of theoretical predictions with the measured values demonstrated that the model tested is well suited for describing the time course of iodine distribution and uptake within the body. It can now be used to study aspects of iodine metabolism relevant to the pharmacological administration of iodine which cannot be investigated experimentally in humans for ethical and technical reasons.

Kinetic of oxidation of methyl orange by vanadium(V) under conditions VO2+ and decavanadates coexist: Catalysis by Triton X-100 micellar medium

2019 ◽  
Author(s):  
Chem Int
Keyword(s):  
Methyl Orange ◽  
Solution Ph ◽  
Vanadium Concentration ◽  
Limiting Behavior ◽  
First Order ◽  
First Order Kinetics ◽  
Ph Range ◽  
Kinetic Pattern ◽  
Triton X ◽  
Kinetics Of

The kinetics of oxidation of methyl orange by vanadium(V) {V(V)} has been investigated in the pH range 2.3-3.79. In this pH range V(V) exists both in the form of decavanadates and VO2+. The kinetic results are distinctly different from the results obtained for the same reaction in highly acidic solution (pH < 1) where V(V) exists only in the form of VO2+. The reaction obeys first order kinetics with respect to methyl orange but the rate has very little dependence on total vanadium concentration. The reaction is accelerated by H+ ion but the dependence of rate on [H+] is less than that corresponding to first order dependence. The equilibrium between decavanadates and VO2+ explains the different kinetic pattern observed in this pH range. The reaction is markedly accelerated by Triton X-100 micelles. The rate-[surfactant] profile shows a limiting behavior indicative of a unimolecular pathway in the micellar pseudophase.

The Kinetics of Glucose Decomposition with Sulfate Reduction in the Anaerobic Fluidized Bed Reactor

1993 ◽  
Vol 28 (2) ◽  
pp. 135-144 ◽  
Author(s):  
S. Matsui ◽  
R. Ikemoto Yamamoto ◽  
Y. Tsuchiya ◽  
B. Inanc
Keyword(s):  
Sulfate Reduction ◽  
Fluidized Bed ◽  
Kinetic Equations ◽  
Fluidized Bed Reactor ◽  
Order Reaction ◽  
First Order Reaction ◽  
First Order ◽  
Glucose Decomposition ◽  
Reaction Equations ◽  
Kinetics Of

Using a fluidized bed reactor, experiments on glucose decomposition with and without sulfate reduction were conducted. Glucose in the reactor was mainly decomposed into lactate and ethanol. Lactate was mainly decomposed into propionate and acetate, while ethanol was decomposed into propionate, acetate, and hydrogen. Sulfate reduction was not involved in the decomposition of glucose, lactate, and ethanol, but was related to propionate and acetate decomposition. The stepwise reactions were modeled using either a Monod expression or first order reaction kinetics in respect to the reactions. The coefficients of the kinetic equations were determined experimentally. The modified Monod and first order reaction equations were effective at predicting concentrations of glucose, lactate, ethanol, propionate, acetate, and sulfate along the beight of the reactor. With sulfate reduction, propionate was decomposed into acetate, while without sulfate reduction, accumulation of propionate was observed in the reactor. Sulfate reduction accelerated propionate conversion into acetate by decreasing the hydrogen concentration.

Submerged upflow biotower operation and computer simulation

1994 ◽  
Vol 30 (11) ◽  
pp. 143-146
Author(s):  
Ronald D. Neufeld ◽  
Christopher A. Badali ◽  
Dennis Powers ◽  
Christopher Carson
Keyword(s):  
Computer Simulation ◽  
Benzoic Acid ◽  
Computer Model ◽  
Rate Constants ◽  
Batch Mode ◽  
Operational Conditions ◽  
First Order ◽  
Low Concentrations ◽  
Biological Transformation ◽  
Kinetics Of

A two step operation is proposed for the biodegradation of low concentrations (< 10 mg/L) of BETX substances in an up flow submerged biotower configuration. Step 1 involves growth of a lush biofilm using benzoic acid in a batch mode. Step 2 involves a longer term biological transformation of BETX. Kinetics of biotransformations are modeled using first order assumptions, with rate constants being a function of benzoic acid dosages used in Step 1. A calibrated computer model is developed and presented to predict the degree of transformation and biomass level throughout the tower under a variety of inlet and design operational conditions.

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