Pharmacokinetics and renal toxicity of three once-a-day doses of amikacin in cows

2005 ◽  
Vol 53 (2) ◽  
pp. 231-240 ◽  
Author(s):  
H. Sumano ◽  
Lilia Gutierrez ◽  
C. Velazquez ◽  
Sayuri Hayashida
Keyword(s):  
Renal Toxicity ◽  
Day Treatment ◽  
Screening Method ◽  
Central Compartment ◽  
Single Daily Dose ◽  
Serum Concentrations ◽  
Maximum Serum ◽  
Elimination Half ◽  
Daily Dose ◽  
Volumes Of Distribution

Pharmacokinetic variables of amikacin in cows were determined after administration of amikacin sulphate either intravenously (IV) or intramuscularly (IM) at a dose of 25 mg/kg per day for three days. Amikacin concentrations at time zero and maximum serum concentrations were 240.8 µg/mL and 122.53 µg/mL, respectively. The elimination half-life remained unchanged during the three days of administration (T½ß = 1.33 ± 0.029 h for the IV route and T½ß = 2.75 ± 0.38 h for the IM route). Apparent volumes of distribution suggest limited distribution out of the central compartment (VdAUC = 0.154 ± 0.005 L/kg; Vdc = 36.50 ± 2.35 L; Vdss = 0.092 ± 0.004 L/kg). Bioavailability after IM administration was 95%. Serum profiles of urea, creatinine, albumin, electrolytes and pH after 5-day treatment with amikacin at a dose of 25 mg/kg per day IM revealed no changes. Assessment of diffusion of amikacin to milk by a commercially available screening method to detect antibiotic residues revealed that amikacin could not be detected by the fifth milking period after the last treatment. These results suggest that it would be rational to use a large single-daily dose of amikacin for future clinical trials in cows.

scholarly journals Population pharmacokinetic study of teicoplanin in severely neutropenic patients.

1996 ◽  
Vol 40 (5) ◽  
pp. 1242-1247 ◽  
Author(s):  
O Lortholary ◽  
M Tod ◽  
N Rizzo ◽  
C Padoin ◽  
O Biard ◽  
...  
Keyword(s):  
Steady State ◽  
Trough Concentration ◽  
Linear Regression Analysis ◽  
Central Compartment ◽  
Population Pharmacokinetic ◽  
Mixed Effect ◽  
Elimination Half ◽  
Neutropenic Patients ◽  
The Mean ◽  
Volumes Of Distribution

The teicoplanin pharmacokinetics (PK) of 30 febrile and severely neutropenic patients (polymorphonuclear count, < 500/mm3) with hematologic malignancies were compared with those determined for five healthy volunteers (HV). Neutropenic patients were given piperacillin combined with amikacin, and teicoplanin was added to the regimen the day fever developed in patients suspected of having a staphylococcal infection or 48 h later. Teicoplanin was given intravenously at a dosage of 6 mg/kg of body weight at 0, 12, and 24 h and once a day thereafter. Five to eleven blood samples per patient were collected. Teicoplanin concentrations were measured by liquid chromatography. A bicompartmental model was fitted to the data by a nonlinear mixed-effect-model approach. Multiple-linear regression analysis was applied in an attempt to correlate PK parameters to nine covariates. The mean trough concentrations of teicoplanin 48 h after the onset of treatment and 24 h after the last injection (last trough) +/- standard deviations were 8.8 +/- 4.1 and 17.5 +/- 13.5 mg/liter, respectively. A significant increase was noted in the mean rate of elimination clearance of teicoplanin in neutropenic patients compared with that of HV (0.86 versus 0.73 liter/h, P = 0.002), as was the case with rates of distribution clearance (5.89 versus 4.94 liter/h, P = 0.002); the mean half-life of distribution was significantly shorter in patients than in HV (0.43 versus 0.61 h, P = 0.002). In contrast, the volumes of the central compartment (ca. 5.8 liters for both groups), the volumes of distribution at steady state (HV, 37.6 liters; patients, 55.9 liters), and the elimination half-lives (HV, 39.6 h; patients, 52.7 h) were not significantly different between HV and neutropenic patients. Interindividual variabilities of rates of clearance (coefficient of variation [CV], 43%) and elimination half-lives (CV, 56%) were mainly explained by the variabilities among rates of creatinine clearance. Interindividual variabilities of the volumes of the central compartment (CV, 33%) and the volumes of distribution at steady state (CV = 51%) were correlated to interindividual variabilities among numbers of leukocytes and the ages of patients, respectively. On the basis of the population PK model of teicoplanin, simulations were made to optimize the dosing schedule. A supplemental 6 mg/kg dose of teicoplanin at 36 h resulted in a trough concentration at 48 h of 16.0 +/- 4.5 mg/liter, with only 7% of patients having a trough concentration of less than 10 mg/liter, compared with 46% of patients on the usual schedule.

Steady-State Serum Concentrations of Dothiepin and Northiaden after Two Dosage Regimens of Dothiepin Hydrochloride (Prothiaden)

1973 ◽  
Vol 1 (2) ◽  
pp. 391-397
Author(s):  
B R S Nakra ◽  
R C Glass ◽  
J A Rees
Keyword(s):  
Steady State ◽  
Parent Drug ◽  
State Level ◽  
Serum Levels ◽  
Single Daily Dose ◽  
Serum Concentrations ◽  
Dosage Regimens ◽  
Daily Dose ◽  
Steady State Serum ◽  
Steady State Levels

Five healthy volunteers took part in a crossover study which examined the serum concentrations of dothiepin and northiaden after a 25 mg three times a day and a 75 mg once a day dosage regimen of Prothiaden. The inter-individual variation of serum levels was large after either schedule which is to be expected with this group of drugs. The minimum steady-state level of dothiepin tended to be lower after the single daily dose, but the differences were small and not statistically significant. The approximate maximum steady-state levels of dothiepin showed large intra- and inter-subject variation and no obvious trend. The values of the desmethylated metabolite, northiaden, tended to follow the dothiepin concentrations but were lower than the parent drug. Average steady-state levels tended, with one exception, to be very similar after both regimens with no evidence of any trend when comparing the two regimens. The study showed that the two regimens yielded similar steady-state serum concentrations both of drug and metabolite but inter-individual differences were large.

Once-Daily Dosing with Phenobarbital in Children with Seizure Disorders

PEDIATRICS ◽  
1981 ◽  
Vol 68 (6) ◽  
pp. 824-827
Author(s):  
Anne G. Davis ◽  
Kelly D. Mutchie ◽  
Joel A. Thompson ◽  
Garth G. Myers
Keyword(s):  
Adverse Reactions ◽  
Pediatric Patients ◽  
Seizure Activity ◽  
Single Daily Dose ◽  
Daily Regimen ◽  
Serum Concentrations ◽  
Once Daily ◽  
Seizure Disorders ◽  
Daily Dose

In nine pediatric patients with seizure disorders, aged 8 months to 16½ years, a single daily dose of phenobarbital was as effective in maintaining therapeutic serum concentrations as twice-daily dosing. There were no adverse reactions to the once-daily regimen, and no seizure activity occurred during the study as a result of the change in dosing pattern.

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.

scholarly journals D-Propranolol Impairs EGFR Trafficking and Destabilizes Mutant p53 Counteracting AKT Signaling and Tumor Malignancy

Cancers ◽  
2021 ◽  
Vol 13 (14) ◽  
pp. 3622
Author(s):  
Jonathan Barra ◽  
Javier Cerda-Infante ◽  
Lisette Sandoval ◽  
Patricia Gajardo-Meneses ◽  
Jenny F. Henriquez ◽  
...  
Keyword(s):  
Therapeutic Potential ◽  
Akt Signaling ◽  
Single Daily Dose ◽  
Mutant P53 ◽  
Inhibitory Pathway ◽  
Recycling Endosomes ◽  
Oncogenic Pathways ◽  
Daily Dose ◽  
High Concentrations ◽  
Novel Therapeutic

Cancer therapy may be improved by the simultaneous interference of two or more oncogenic pathways contributing to tumor progression and aggressiveness, such as EGFR and p53. Tumor cells expressing gain-of-function (GOF) mutants of p53 (mutp53) are usually resistant to EGFR inhibitors and display invasive migration and AKT-mediated survival associated with enhanced EGFR recycling. D-Propranolol (D-Prop), the non-beta blocker enantiomer of propranolol, was previously shown to induce EGFR internalization through a PKA inhibitory pathway that blocks the recycling of the receptor. Here, we first show that D-Prop decreases the levels of EGFR at the surface of GOF mutp53 cells, relocating the receptor towards recycling endosomes, both in the absence of ligand and during stimulation with high concentrations of EGF or TGF-α. D-Prop also inactivates AKT signaling and reduces the invasive migration and viability of these mutp53 cells. Unexpectedly, mutp53 protein, which is stabilized by interaction with the chaperone HSP90 and mediates cell oncogenic addiction, becomes destabilized after D-Prop treatment. HSP90 phosphorylation by PKA and its interaction with mutp53 are decreased by D-Prop, releasing mutp53 towards proteasomal degradation. Furthermore, a single daily dose of D-Prop reproduces most of these effects in xenografts of aggressive gallbladder cancerous G-415 cells expressing GOF R282W mutp53, resulting in reduced tumor growth and extended mice survival. D-Prop then emerges as an old drug endowed with a novel therapeutic potential against EGFR- and mutp53-driven tumor traits that are common to a large variety of cancers.

Legumin from chickpea: hypolipidemic effect in the liver of hypercholesterolemic rats

2014 ◽  
Vol 44 (5) ◽  
pp. 378-388 ◽  
Author(s):  
Ana L. Amaral ◽  
Ederlan S. Ferreira ◽  
Valdir A. Neves ◽  
Aureluce Demonte
Keyword(s):  
Lipid Metabolism ◽  
Cholic Acid ◽  
Hdl Cholesterol ◽  
Normal Diet ◽  
Single Daily Dose ◽  
High Cholesterol Diet ◽  
Hypolipidemic Effect ◽  
Content Type ◽  
Daily Dose ◽  
11S Globulin

Purpose – This paper aims to determine the effects of 11S globulin isolated from Chickpea (Cicer arietinum L.) on lipid metabolism in animals subjected to a hypercholesterolemic and hyperlipidemic diet and compared to the drug simvastatin. Design/methodology/approach – Thirty-six male Wistar rats, kept in individual cages and under appropriate conditions, were separated into groups that were fed a normal diet (STD) containing casein as protein source and according to AIN-93G; a high-cholesterol diet (HC), normal diet plus 1 per cent cholesterol and 0.5 per cent cholic acid and 20 per cent coconut oil; HC diet plus the isolated 11S globulin (300 mg/kg/day); and HC diet plus the simvastatin (50 mg/kg/day), both dissolved in saline and administered by gavage for 28 days. After this time, the animals were killed. Findings – The results indicated that the addition of 1 per cent cholesterol and 0.5 per cent cholic acid induced hypercholesterolemia in the animals without interfering with their weight gain. Analyses of total cholesterol (TC), HDL-cholesterol (HDL-C) and triglycerides (TG) in the plasma, and TC and TG in the liver were made. The results show that the protein isolated from chickpea, and given as a single daily dose, did not affect the levels of plasma TC and its fractions, although decreasing the TG levels. Unlike the simvastatin, the chickpea protein significantly reduced TC and TG in the liver relative to HC group. Originality/value – A single daily dose of 11S globulin from chickpea contributed as only as additional 2.8 per cent of dietary protein intake. These findings demonstrate that 11S chickpea protein acts as a functional agent in the lipid metabolism in addition to its nutritional properties.

A note on rumen ammonia and blood urea levels in steers administered urea or sparingly soluble urea derivates as nitrogen supplements

1977 ◽  
Vol 24 (1) ◽  
pp. 117-119 ◽  
Author(s):  
R. N. Pal ◽  
S. S. Negi
Keyword(s):  
Single Daily Dose ◽  
Paddy Straw ◽  
Daily Dose

SUMMARYRuminal ammonia and blood urea levels were compared in fistulated steers eating paddy straw to appetite and given urea alone, urea plus oxalate, and complexes of urea with either formaldehyde (UFC) or oxalate (UOC), introduced into the rumen in a single daily dose. The solubilities of UFC and UOC in rumen liquor were 23·7 and 4·6% respectively of that of urea. Higher levels of ruminal ammonia and blood urea were recorded on urea than on other supplements.

Assessment of the Antihypertensive Effect of Atenolol with 24 H Ambulatory Monitoring of Blood Pressure

1979 ◽  
Vol 57 (s5) ◽  
pp. 387s-389s ◽  
Author(s):  
J. S. Floras ◽  
P. Fox ◽  
M. O. Hassan ◽  
J. V. Jones ◽  
P. Sleight ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Essential Hypertension ◽  
Arterial Blood Pressure ◽  
Antihypertensive Effect ◽  
Ambulatory Monitoring ◽  
Single Daily Dose ◽  
Pressure Measurements ◽  
Arterial Blood ◽  
Blood Pressure Study ◽  
Daily Dose

1. Twenty-four hour intra-arterial blood pressure measurements and electrocardiograms were obtained from 12 subjects with untreated essential hypertension. 2. The patients kept records of their activity, paying particular attention to times of retiring to bed, and times of waking in the morning. 3. All subjects were treated with a single daily dose of atenolol (50 to 200 mg) for between 2 and 9 months, and then underwent a second 24 h blood pressure study. 4. Arterial blood pressure was lowered significantly throughout the 24 h period with a single daily dose of atenolol.

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