Chronopharmacology of β-Adrenoceptor-Blocking Drugs: Pharmacokinetic and Pharmacodynamic Studies in Rats

1983 ◽  
Vol 2 (6) ◽  
pp. 347-358 ◽  
Author(s):  
B. Lemmer ◽  
K. Bathe ◽  
P. H. Lang ◽  
G. Neumann ◽  
H. Winkler
Keyword(s):  
Treatment Time ◽  
Human Subjects ◽  
Temporal Variations ◽  
Male Rats ◽  
Pharmacokinetic Parameters ◽  
Nonspecific Effects ◽  
Elimination Half ◽  
Receptor Blockers ◽  
Β Receptor ◽  
Kinetics Of

Specific and nonspecific effects and the pharmacokinetic behavior of β-adrenoceptor-blocking drugs of different Iipophilicity (atenolol, bupranolol, carazolol, metoprolol, ox-prenolol, practolol, propranolol, sotalol) were investigated in L-D-synchronized male rats as a function of treatment time. The studies revealed that pharmacodynamic effects on heart rate, cardiac noradrenaline turnover, and motor activity as well as pharmacokinetic parameters of racemic mixtures of β-receptor blockers display temporal variations with more pronounced pharmacological effects and shorter elimination half-lives in the dark span. Studies with the isomers of bupranolol and practolol indicate no stereospecificity in the central depressant effect; the kinetic behavior of, for example, propranolol, however, exhibits stereospecificity. The results demonstrate the importance of circadian rhythms in modifying the effects and kinetics of drugs. These findings may have therapeutic implication in human subjects.

A fuzzy neural network approach for modeling the growth kinetics of FeB and Fe2B layers during the boronizing process

2018 ◽  
Vol 106 (6) ◽  
pp. 603 ◽  
Author(s):  
Bendaoud Mebarek ◽  
Mourad Keddam
Keyword(s):  
Neural Network ◽  
Experimental Data ◽  
Fuzzy Neural Network ◽  
Treatment Time ◽  
Calculation Model ◽  
Average Error ◽  
Network Approach ◽  
Neural Network Approach ◽  
Fuzzy Neural ◽  
Kinetics Of

In this paper, we develop a boronizing process simulation model based on fuzzy neural network (FNN) approach for estimating the thickness of the FeB and Fe2B layers. The model represents a synthesis of two artificial intelligence techniques; the fuzzy logic and the neural network. Characteristics of the fuzzy neural network approach for the modelling of boronizing process are presented in this study. In order to validate the results of our calculation model, we have used the learning base of experimental data of the powder-pack boronizing of Fe-15Cr alloy in the temperature range from 800 to 1050 °C and for a treatment time ranging from 0.5 to 12 h. The obtained results show that it is possible to estimate the influence of different process parameters. Comparing the results obtained by the artificial neural network to experimental data, the average error generated from the fuzzy neural network was 3% for the FeB layer and 3.5% for the Fe2B layer. The results obtained from the fuzzy neural network approach are in agreement with the experimental data. Finally, the utilization of fuzzy neural network approach is well adapted for the boronizing kinetics of Fe-15Cr alloy.

Influence of cyp2d6 polymorphisms on pharmacokinetics, efficacy and safety of antipsychotics

2018 ◽  
pp. 26-39
Author(s):  
А.А. Курылев ◽  
Б.В. Андреев
Keyword(s):  
Genetic Polymorphisms ◽  
Atypical Antipsychotics ◽  
Retrospective Studies ◽  
Pharmacokinetic Parameters ◽  
Clinical Routine ◽  
Elimination Half ◽  
Daily Dose ◽  
Comparison Groups ◽  
Cyp2d6 Polymorphisms ◽  
Positive Significant Correlation

Несмотря на доступность в клинической практике широкого круга классических и атипичных антипсихотиков (АП), по-прежнему наблюдается широкая вариабельность ответа на психофармакотерапию. Эта вариабельность обусловлена генетической гетерогенностью как самой шизофрении, так и метаболизма АП. Стандартные назначаемые дозы АП далеко не всегда являются оптимальными. Генетическая вариабельность систем биотрансформации и биодоступности АП могут играть значимую роль в формировании ответа на терапию и развитии нежелательных реакций. Целью исследования стало проведение обзора литературы по проблеме клинической эффективности применения генотипирования полиморфизмов CYP2D6 при терапии антипсихотиками. Большинство фармакокинетических исследований обнаруживают сильную достоверную положительную корреляцию метаболического статуса CYP2D6, определенного путем генотипирования полиморфизмов CYP2D6 и фармакокинетических параметров АП (AUC, период полувыведения, клиренс). Однако статистически достоверных связей между полиморфизмами CYP2D6 и эффективностью терапии АП в большинстве исследований обнаружено не было, прежде всего из-за недостаточного количества участников, гетерогенности сравниваемых когорт, применении различных АП и использовании разных критериев эффективности. Перспективные исследования с хорошо сбалансированными группами сравнения, а также масштабные ретроспективные исследования демонстрируют достоверную корреляцию метаболического статуса CYP2D6 и частоты развития нежелательных реакций АП (лекарственный паркинсонизм и поздняя дискинезия). Для более точной оценки величины вклада генетических полиморфизмов CYP2D6 в эффективность и безопасность психофармакотерапии необходимы масштабные перспективные клинические исследования. Although a number of typical and atypical antipsychotics (AP) have been discovered and used in psychiatric clinical practice the variability in response to AP is quite high. This variability is partially explained by a genetic heterogeneity of schizophrenia and metabolism of AP. The standard prescribed antipsychotic daily dose is not always optimal. Genetic variability of biotransformation and bioavailability of AP may significantly influence on therapeutic effect and tolerability. The aim of the study was to perform literature review of studies evaluating the correlation of CYP2D6 genetic polymorphisms and AP pharmacokinetics, effectiveness and safety. Most pharmacokinetics studies show high positive significant correlation between CYP2D6 metabolic activity, determined by CYP2D6 polymorphisms genotyping and AP pharmacokinetic parameters (AUC, elimination half-life, clearance etc.). However the majority of studies were failed to demonstrate significant correlation between CYP2D6 polymorphisms and AP effectiveness mainly due to inadequate number of patient, heterogeneous cohorts, different AP and effectiveness criteria used. Prospective studies with balanced comparison groups and large retrospective studies showed significant correlation between CYP2D6 metabolic status and the frequency of AP induced AEs (parkinsonism and tardive dyskinesia). To better assess the influence of CYP2D6 genetic polymorphisms on AP effectiveness and safety in clinical routine large prospective well designed clinical studies are needed.

Ethylene Glycol and Glycerin as the Solvent for Alkaline Treatment of Poly(ethylene Terephthalate) Fabrics

1997 ◽  
Vol 67 (10) ◽  
pp. 760-766 ◽  
Author(s):  
M.-C. Yang ◽  
H.-Y. Tsai
Keyword(s):  
Ethylene Glycol ◽  
Degradation Rate ◽  
Ethylene Terephthalate ◽  
Treatment Time ◽  
Alkaline Treatment ◽  
Aqueous System ◽  
Poly Ethylene Terephthalate ◽  
Poly Ethylene ◽  
Kinetics Of ◽  
Scanning Electron

Poly(ethylene terephthalate) fabrics are treated with sodium hydroxide using ethylene glycol or glycerin as the solvent. Compared with conventional aqueous alkaline hydrolysis, the degradation rate in ethylene glycol increases tenfold. The kinetics of the alkaline-ethylene glycol treatment show that the weight loss is linear with respect to time. The moisture regain rate and tensile properties of the treated fabrics are measured; other tests include scanning electron microscopy and dyeing properties. The results show that the properties of the treated fabrics do not depend significantly on the solvent; therefore, using ethylene glycol can greatly shorten the treatment time to achieve results similar to those with the conventional aqueous system.

scholarly journals Serum bactericidal activities and comparative pharmacokinetics of meropenem and imipenem-cilastatin.

1996 ◽  
Vol 40 (1) ◽  
pp. 105-109 ◽  
Author(s):  
M Dreetz ◽  
J Hamacher ◽  
J Eller ◽  
K Borner ◽  
P Koeppe ◽  
...  
Keyword(s):  
Compartment Model ◽  
Pharmacokinetic Parameters ◽  
Time Curve ◽  
Dose Administration ◽  
Microdilution Method ◽  
Two Compartment Model ◽  
Elimination Half ◽  
Renal Clearances ◽  
The Mean ◽  
Bactericidal Activities

The pharmacokinetics and serum bactericidal activities (SBAs) of imipenem and meropenem were investigated in a randomized crossover study. Twelve healthy male volunteers received a constant 30-min infusion of either 1 g of imipenem plus 1 g of cilastatin or 1 g of meropenem. The concentrations of the drugs in serum and urine were determined by bioassay and high-pressure liquid chromatography. Pharmacokinetic parameters were based on an open two-compartment model and a noncompartmental technique. At the end of infusion, the mean concentrations of imipenem and meropenem measured in serum were 61.2 +/- 9.8 and 51.6 +/- 6.5 mg/liter, respectively; urinary recoveries were 48.6% +/- 8.2% and 60.0% +/- 6.5% of the dose in 12 h, respectively; and the areas under the concentration-time curve from time zero to infinity were 96.1 +/- 14.4 and 70.5 +/- 10.3 mg.h/liter, respectively (P < or = 0.02). Imipenem had a mean half-life of 66.7 +/- 10.4 min; that of meropenem was 64.4 +/- 6.9 min. The volumes of distribution at steady state of imipenem and meropenem were 15.3 +/- 3.3 and 18.6 +/- 3.0 liters/70 kg, respectively, and the mean renal clearances per 1.73 m2 were 85.6 +/- 17.6 and 144.6 +/- 26.0 ml/min, respectively. Both antibiotics were well tolerated in this single-dose administration study. The SBAs were measured by the microdilution method of Reller and Stratton (L. B. Reller and C. W. Stratton, J. Infect. Dis. 136:196-204, 1977) against 40 clinically isolated strains. Mean reciprocal bactericidal titers were measured 1 and 6 h after administration. After 1 and 6 h the median SBAs for imipenem and meropenem, were 409 and 34.9 and 97.9 and 5.8, respectively, against Staphylococcus aureus, 19.9 and 4.4 and 19.4 and 4.8, respectively, against Pseudomonas aeruginosa, 34.3 and 2.2 and 232 and 15.5, respectively, against Enterobacter cloacae, and 13.4 and 2.25 and 90.7 and 7.9, respectively, against Proteus mirabilis. Both drugs had rather short biological elimination half-lives and a predominantly renal route of elimination. Both carbapenems revealed high SBAs against clinically important pathogens at 1 h; meropenem had a higher SBA against E. cloacae and P. mirabilis, and the SBA of imipenem against S. aureus was greater than the SBA of meropenem.

scholarly journals Kinetics of the Post-Onset Decline in Zinc Transporter 8 Autoantibodies in Type 1 Diabetic Human Subjects

2010 ◽  
Vol 95 (10) ◽  
pp. 4712-4719 ◽  
Author(s):  
J. M. Wenzlau ◽  
M. Walter ◽  
T. J. Gardner ◽  
L. M. Frisch ◽  
L. Yu ◽  
...  
Keyword(s):  
Human Subjects ◽  
Zinc Transporter ◽  
Zinc Transporter 8 ◽  
Kinetics Of ◽  
Post Onset

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 Toxicity and Pharmacokinetic Studies of Lidocaine and Its Active Metabolite, Monoethylglycinexylidide, in Goat Kids

Animals ◽  
2018 ◽  
Vol 8 (8) ◽  
pp. 142
Author(s):  
Dinakaran Venkatachalam ◽  
Paul Chambers ◽  
Kavitha Kongara ◽  
Preet Singh
Keyword(s):  
Total Dose ◽  
Plasma Concentrations ◽  
Subcutaneous Administration ◽  
Lidocaine Hydrochloride ◽  
Pharmacokinetic Parameters ◽  
Pharmacokinetic Studies ◽  
Liquid Chromatography Mass Spectrometry ◽  
Elimination Half ◽  
The Mean ◽  
Safe Dose

This study determined the convulsant plasma concentrations and pharmacokinetic parameters following cornual nerve block and compared the results to recommend a safe dose of lidocaine hydrochloride for goat kids. The plasma concentrations of lidocaine and monoethylglycinexylidide (MGX) were quantified using liquid chromatography-mass spectrometry. A total dose of 7 mg/kg body weight (BW) was tolerated and should therefore be safe for local and regional anesthesia in goat kids. The mean plasma concentration and mean total dose that produced convulsions in goat kids were 13.59 ± 2.34 µg/mL and 12.31 ± 1.42 mg/kg BW (mean ± S.D.), respectively. The absorption of lidocaine following subcutaneous administration was rapid with Cmax and Tmax of 2.12 ± 0.81 µg/mL and 0.33 ± 0.11 h, respectively. The elimination half-lives (t½λz) of lidocaine hydrochloride and MGX were 1.71 ± 0.51 h and 3.19 ± 1.21 h, respectively. Injection of 1% lidocaine hydrochloride (0.5 mL/site) was safe and effective in blocking the nerves supplying horn buds in goat kids.

scholarly journals Pharmacokinetics of α-Pyrrolidinovalerophenone in Male Rats with and without Vaccination with an α-Pyrrolidinovalerophenone Vaccine

2021 ◽  
Vol 24 ◽  
pp. 267-276
Author(s):  
Samantha McClenahan ◽  
Melinda Gunnell ◽  
Michael Owens
Keyword(s):  
Treatment Time ◽  
Area Under The Curve ◽  
Early Time ◽  
Volume Of Distribution ◽  
Male Rats ◽  
Serum Concentrations ◽  
Sprague Dawley ◽  
Serum Samples ◽  
Maximum Serum ◽  
The Brain

PURPOSE: α-Pyrrolidinovalerophenone (α-PVP) is a second-generation synthetic cathinone which acts as an inhibitor at the dopamine and norepinephrine transporters in the brain. These novel studies determined the pharmacokinetics (PK) of α-PVP in rats and then evaluated the effects of an α-PVP vaccine on the PK profile. METHODS: Adult male Sprague-Dawley rats were randomly divided into treatment groups (n = 24/group) in which the vaccinated rats received an initial and two booster immunizations of the α-PVP vaccine at 0, 3, and 9 wks. Control rats received saline injections. α-PVP (0.56, 1, 3 mg/kg, sc) was then administered to both groups between 11-12 weeks and serum samples were collected for determination of α-PVP serum concentrations by LC-MS/MS (n=6 rats/treatment/time). At 13 weeks, brain, heart and kidney concentrations of α-PVP were determined by LC-MS/MS after administration of 1 mg/kg α-PVP (n=4-5 rats/treatment/time). RESULTS: PK values in control rats showed dose-dependent increases in maximum serum concentrations (Cmax) and area under the curve (AUCinf) values with an elimination half-life (t1/2) of approximately 2.1 h. α-PVP exhibited linear PK profile in control rats. Vaccinated rats had significantly (p<0.05) higher serum Cmax and AUCinf values than controls, and significantly reduced total body clearance, volume of distribution and t1/2 values. Vaccinated rats had significantly lower α-PVP concentrations in the brain, heart, and kidney in comparison to control rats at early time points. CONCLUSION: Vaccination with the novel α-PVP vaccine significantly altered serum PK leading to a time-dependent reduction in brain, kidney and heart concentrations of α-PVP compared to controls.

scholarly journals Safety, toleration, and pharmacokinetics of intravenous azithromycin.

1996 ◽  
Vol 40 (11) ◽  
pp. 2577-2581 ◽  
Author(s):  
D R Luke ◽  
G Foulds ◽  
S F Cohen ◽  
B Levy
Keyword(s):  
Half Life ◽  
Active Drug ◽  
Slow Release ◽  
Volume Of Distribution ◽  
Pharmacokinetic Parameters ◽  
Time Curve ◽  
Concentration Time ◽  
Elimination Half ◽  
The Mean ◽  
Male Subjects

To date, the clinical pharmacology of large intravenous doses of azithromycin has not been described. In the present study, single 2-h intravenous infusions of 1, 2, and 4 g of azithromycin were administered to three parallel groups (in each group, six received active drug and two received placebo) of healthy male subjects. Toleration (assessed by scores of subject-administered visual analog scale tests spanning 0 [good] to 10 [poor]), safety, pharmacokinetics, and serum motilin levels were monitored for up to 240 h after the start of each intravenous infusion. Mean nausea scores of 0.0, 0.0, 1.0, and 0.5 and abdominal cramping scores of 0.0, 0.0, 0.4, and 0.4 for 12-h periods after doses of 0, 1, 2, and 4 g of azithromycin, respectively, suggested that azithromycin was well tolerated. Because of the standardized 1-mg/ml infusates, all subjects in the 4-g dosing group complained of an urgent need to urinate. There were no consistent trends in endogenous motilin levels throughout the study. The maximum concentration of azithromycin in serum (10 micrograms/ml after a 4-g dose) and the area under the concentration-time curve (82 micrograms.h/ml after a 4-g dose) were dose related. The mean pharmacokinetic parameters were an elimination half-life of 69 h, total systemic clearance of 10 ml/min/kg, and a volume of distribution at steady state of 33.3 liters/kg. The pharmacokinetic results suggest that the long half-life of azithromycin is due to extensive uptake and slow release of the drug from tissues rather than an inability to clear the drug. Single intravenous doses of up to 4 g of azithromycin in healthy subjects are generally well tolerated, and quantifiable concentrations may persist in serum for 10 days or more.

Sign in / Sign up

Export Citation Format

Share Document