scholarly journals Pharmacokinetic modelling of valproate in epileptic patients

2010 ◽  
Vol 63 (5-6) ◽  
pp. 349-355
Author(s):  
Mihajlo Jakovljevic ◽  
Slobodan Jankovic ◽  
Natalija Todorovic ◽  
Jasmina Milovanovic ◽  
Snezana Jankovic
Keyword(s):  
Body Weight ◽  
Pharmacokinetic Model ◽  
Model Building ◽  
Total Body Weight ◽  
Mean Value ◽  
Total Daily Dose ◽  
Population Pharmacokinetic ◽  
Mean Values ◽  
Epileptic Patients ◽  
Total Body

Introduction. The aim of our study was to develop and use a population pharmacokinetic model for assessment of individual valproate clearance in children and young adults suffering from epilepsy. Material and methods. The analysis was performed using 52 steady-state concentrations of valproate collected from 26 epileptic patients during the routine clinical practice in our hospital. The mean values of age and total body weight were 19.92 years and 57.12 kg, respectively. NONMEM software with ADVAN 1 subroutine was used for model building and assessing the influence of different covariates. A validation set of 20 epileptic patients (one blood sample per a patient) was used to estimate predicted performances of the pharmacokinetic model. Results. The typical mean value of the clearance of valproate estimated by the base model in our population was 0.377 l/h. Out of five considered covariates (total body weight, age, total daily dose, gender and polytherapy) only the age of the patients was a significant determinant of the clearance of valproate. The final regression model for the clearance of valproate was as following: CL (l/h) = 0.223 + 0.00819

scholarly journals Population Pharmacokinetic Analyses for Ertapenem in Subjects with a Wide Range of Body Sizes

2018 ◽  
Vol 62 (10) ◽  
Author(s):  
Elizabeth A. Lakota ◽  
Cornelia B. Landersdorfer ◽  
Li Zhang ◽  
Anne N. Nafziger ◽  
Joseph S. Bertino ◽  
...  
Keyword(s):  
Body Weight ◽  
Population Pharmacokinetic Model ◽  
Pharmacokinetic Model ◽  
Interindividual Variability ◽  
Total Body Weight ◽  
Pharmacokinetic Parameters ◽  
Population Pharmacokinetic ◽  
Wide Range ◽  
Body Sizes ◽  
Total Body

ABSTRACTDespite a number of studies reporting that ertapenem pharmacokinetic parameters differ considerably in obese patients from those in healthy volunteers, functions describing the relationships between this agent's pharmacokinetics and indicators of body size have not been developed. The aim of this analysis was to develop an ertapenem population pharmacokinetic model using data from a previously described study in normal-weight, obese, and morbidly obese healthy volunteers. A single ertapenem 1-g dose administered intravenously was evaluated in 30 subjects within different body mass index (BMI) categories. The population pharmacokinetic model was developed using the first-order conditional estimation method with interaction (FOCE-I) algorithm within NONMEM. The ability of age, sex, renal function, and various body size measures (total body weight, height, body mass index, ideal body weight, fat-free mass, and body surface area [BSA]) to explain a portion of the interindividual variability on select pharmacokinetic parameters was explored using stepwise forward selection (α = 0.01) and backward elimination (α = 0.001). The data were best described using a linear three-compartment model with total body weight as a covariate on clearance (CL = 1.79 · [weight/95.90]0.278) and BSA as a covariate on central volume (Vc = 4.76 · [BSA/2.06]1.86). After accounting for fixed effects, the estimated interindividual variability was very low (<10% for all clearance and volume terms). Goodness-of-fit diagnostics indicated a precise and unbiased fit to the data. Using the developed population pharmacokinetic model and simulation, reliable estimates of ertapenem serum exposures, which can be utilized to evaluate various dosing regimens in subjects with a wide range of body sizes, are expected.

Population pharmacokinetics of diethylcarbamazine in patients with lymphatic filariasis and healthy individuals

2021 ◽  
Author(s):  
Veenu Bala ◽  
Yashpal S Chhonker ◽  
Abdullah Alshehri ◽  
Constant Edi ◽  
Catherine M Bjerum ◽  
...  
Keyword(s):  
Body Weight ◽  
Lymphatic Filariasis ◽  
Population Pharmacokinetic Model ◽  
Pharmacokinetic Model ◽  
Model Building ◽  
The Body ◽  
Population Pharmacokinetic ◽  
Healthy Individuals ◽  
Female Population ◽  
Final Population

Diethylcarbamazine (DEC) is a drug of choice to treat lymphatic filariasis (LF) either used alone or in combination as mass drug administration (MDA) preventive strategies. The objective of this study was to develop a population pharmacokinetic model for DEC in subjects infected with lymphatic filariasis (LF) compared to healthy individuals, and to evaluate the effect of covariates on the volume of distribution (V/F) and oral clearance (CL/F) of DEC. This was an open-label cohort study of treatment naïve Wuchereria bancrofti -infected (n=32) and uninfected (n=24) adults residing in the Agboville district of Côte d’Ivoire. The population pharmacokinetic model for DEC was built using Phoenix NLME 8.0 software. The covariates included in the model building process were age, gender, bodyweight, infection status, creatinine clearance (CrCl), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels. A total of 56 adults were enrolled in the study and a total of 728 samples were obtained over 168 hours. A one-compartment linear pharmacokinetic model with first-order absorption with an absorption lag-time (Tlag) best described the data. After determining the pharmacokinetics (PK) parameters of DEC, body weight and gender were found to be the significant covariates for DEC V/F. The final population pharmacokinetic model adequately described the pharmacokinetics of DEC in the studied population. Model-based simulation indicated that the body weight significantly impacted the exposure in both the male and female population. This analysis may further support the drug-drug interaction model development of DEC with different co-administered drugs/agents in disease control programs.

scholarly journals Pharmacokinetics of Telavancin in Adult Patients with Cystic Fibrosis during Acute Pulmonary Exacerbation

2019 ◽  
Vol 64 (1) ◽  
Author(s):  
James M. Kidd ◽  
Colleen M. Sakon ◽  
Louise-Marie Oleksiuk ◽  
Jeffrey J. Cies ◽  
Rebecca S. Pettit ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Body Weight ◽  
Total Body Weight ◽  
Central Compartment ◽  
Volume Of Distribution ◽  
Peripheral Compartment ◽  
Population Pharmacokinetic ◽  
Minimal Risk ◽  
Content Type ◽  
Total Body

ABSTRACT Adults with cystic fibrosis (CF) frequently harbor Staphylococcus aureus, which is increasingly antibiotic resistant. Telavancin is a once-daily rapidly bactericidal antibiotic active against methicillin-, linezolid-, and ceftaroline-resistant S. aureus. Because CF patients experience alterations in pharmacokinetics, the optimal dose of telavancin in this population is unknown. Adult CF patients (n = 18) admitted for exacerbations received 3 doses of telavancin 7.5 mg/kg of body weight (first 6 patients) or 10 mg/kg (final 12 patients) every 24 h (q24h). Population pharmacokinetic models with and without covariates were fitted using the nonparametric adaptive grid algorithm in Pmetrics. The final model was used to perform 5,000-patient Monte Carlo simulations for multiple telavancin doses. The best fit was a 2-compartment model describing the volume of distribution of the central compartment (Vc) as a multiple of total body weight (TBW) and the volume of distribution of the central compartment scaled to total body weight (Vθ) normalized by the median observed value (Vc = Vθ × TBW/52.1) and total body clearance (CL) as a linear function of creatinine clearance (CRCL) (CL = CLNR + CLθ × CRCL), where CLNR represents nonrenal clearance and CLθ represents the slope term on CRCL to estimate renal clearance. The mean population parameters were as follows: Vθ, 4.92  ± 0.76 liters · kg−1; CLNR, 0.59  ± 0.30 liters · h−1; CLθ, 5.97 × 10−3 ± 1.24 × 10−3; Vp (volume of the peripheral compartment), 3.77  ± 1.41 liters; Q (intercompartmental clearance), 4.08  ± 2.17 liters · h−1. The free area under the concentration-time curve (fAUC) values for 7.5 and 10 mg/kg were 30  ± 4.6 and 52  ± 12 mg · h/liter, respectively. Doses of 7.5 mg/kg and 10 mg/kg achieved 76.5% and 100% probability of target attainment (PTA) at a fAUC/MIC threshold of >215, respectively, for MIC of ≤0.12 mg/liter. The probabilities of reaching the acute kidney injury (AKI) threshold AUC (763 mg · h · liter−1) for these doses were 0% and 0.96%, respectively. No serious adverse events occurred. Telavancin 10 mg/kg yielded optimal PTA and minimal risk of AKI, suggesting that this FDA-approved dose is appropriate to treat acute pulmonary exacerbations in CF adults. (The clinical trial discussed in this study has been registered at ClinicalTrials.gov under identifier NCT03172793.)

Does the Atlantic bonito, Sarda sarda, spawn in the eastern Adriatic Sea?

2019 ◽  
Vol 99 (8) ◽  
pp. 1865-1868
Author(s):  
Vanja Čikeš Keč ◽  
Barbara Zorica ◽  
Vedran Vuletin
Keyword(s):  
Body Weight ◽  
Adriatic Sea ◽  
Gonadosomatic Index ◽  
Fork Length ◽  
Total Body Weight ◽  
Mean Value ◽  
Four Seasons ◽  
Increasing Trend ◽  
Total Body ◽  
Sarda Sarda

AbstractAtlantic bonito, Sarda sarda, is one of the representatives of the Scombridae family in the Adriatic Sea. Larvae and juveniles have been found and described in the area, but no information has been published regarding adults spawning in the Adriatic Sea. To explore the strong possibility that Atlantic bonito are reproducing in the Adriatic Sea, 122 specimens of adult Atlantic bonito were collected from a purse seine net ‘palamidara’ over four seasons in 2017. The fork length of the analysed specimens varied from 37.5 to 60.8 cm, with a mean of 48.83 ± 5.59 cm, while total body weight varied between 742.68 and 3102.59 g, with a mean value of 1700.49 ± 543.82 g. Gonadosomatic index values showed an increasing trend from autumn (0.123 for males, 0.897 for females) until spring, while in the summer, they reached their maximum values (3.609 for males, 5.604 for females). This trend was also confirmed by histological and macroscopic analyses of gonads, which suggested that the Atlantic bonito spawning season is in the spring-summer in the Adriatic Sea. Hence, this confirms that this species is spawning in the Adriatic Sea.

Body oxygen consumption and pulmonary ventilation in obese subjects

1965 ◽  
Vol 20 (2) ◽  
pp. 197-201 ◽  
Author(s):  
Robert I. White ◽  
James K. Alexander
Keyword(s):  
Body Weight ◽  
Oxygen Consumption ◽  
Body Surface ◽  
Basal Metabolic Rate ◽  
Cell Mass ◽  
Total Body Weight ◽  
Mean Values ◽  
Obese Subjects ◽  
The Mean ◽  
Total Body

Postabsorptive body oxygen consumption (Vo2) and pulmonary minute ventilation (Ve) were measured 164 times in 109 very obese subjects at rest. A statistically significant relationship was found between Vo2 and total body weight. The correlation coefficients for the relationships between Ve and total body weight and Ve and body surface area were less significant. The mean calculated basal metabolic rate was within normal limits. The mean values for Vo2 in the obese subjects were considerably higher than those predicted at ideal weight, while the mean values for oxygen consumption per kilogram body weight were lower than those reported in normal subjects. The mean percentage increase in oxygen consumption per kilogram excess weight (ΔVo2/Δ kg) approached the value for percentage of cell mass in excess weight, suggesting that ΔVo2/Δ kg may be a function of the increment in cell mass with obesity. Similarly, since basal metabolic rate remained unchanged, proportionate increments in body surface area and cell mass appeared to occur with the development of obesity. obesity tissue, oxygen consumption Submitted on April 3, 1964

scholarly journals Lean body weight versus total body weight to calculate the iodinated contrast media volume in abdominal CT: a randomised controlled trial

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Moreno Zanardo ◽  
Fabio Martino Doniselli ◽  
Anastassia Esseridou ◽  
Massimiliano Agrò ◽  
Nicol Antonina Rita Panarisi ◽  
...  
Keyword(s):  
Body Weight ◽  
Contrast Media ◽  
Controlled Trial ◽  
Total Body Weight ◽  
Lean Body Weight ◽  
Iodinated Contrast Media ◽  
Abdominal Ct ◽  
Iodinated Contrast ◽  
Significant Difference ◽  
Total Body

Abstract Objectives Iodinated contrast media (ICM) could be more appropriately dosed on patient lean body weight (LBW) than on total body weight (TBW). Methods After Ethics Committee approval, trial registration NCT03384979, patients aged ≥ 18 years scheduled for multiphasic abdominal CT were randomised for ICM dose to LBW group (0.63 gI/kg of LBW) or TBW group (0.44 gI/kg of TBW). Abdominal 64-row CT was performed using 120 kVp, 100–200 mAs, rotation time 0.5 s, pitch 1, Iopamidol (370 mgI/mL), and flow rate 3 mL/s. Levene, Mann–Whitney U, and χ2 tests were used. The primary endpoint was liver contrast enhancement (LCE). Results Of 335 enrolled patients, 17 were screening failures; 44 dropped out after randomisation; 274 patients were analysed (133 LBW group, 141 TBW group). The median age of LBW group (66 years) was slightly lower than that of TBW group (70 years). Although the median ICM-injected volume was comparable between groups, its variability was larger in the former (interquartile range 27 mL versus 21 mL, p = 0.01). The same was for unenhanced liver density (IQR 10 versus 7 HU) (p = 0.02). Median LCE was 40 (35–46) HU in the LBW group and 40 (35–44) HU in the TBW group, without significant difference for median (p = 0.41) and variability (p = 0.23). Suboptimal LCE (< 40 HU) was found in 64/133 (48%) patients in the LBW group and 69/141 (49%) in the TBW group, but no examination needed repeating. Conclusions The calculation of the ICM volume to be administered for abdominal CT based on the LBW does not imply a more consistent LCE.

Increases in adipose and total body weight, but not in lean body mass, associated with subcutaneous administration of Sonic hedgehog-Ig fusion protein to mice

2002 ◽  
Vol 57 (3) ◽  
pp. 107-114 ◽  
Author(s):  
Pauline L. Martin ◽  
Joan Lane ◽  
Louise Pouliot ◽  
Malcolm Gains ◽  
Rudolph Stejskal ◽  
...  
Keyword(s):  
Body Weight ◽  
Fusion Protein ◽  
Lean Body Mass ◽  
Body Mass ◽  
Sonic Hedgehog ◽  
Subcutaneous Administration ◽  
Total Body Weight ◽  
Total Body

Effects of the teratogenic folic acid antagonist, 9-methyl pteroylglutamic acid, on hydroxyproline levels in fetal rat limbs

Development ◽  
1977 ◽  
Vol 41 (1) ◽  
pp. 289-294
Author(s):  
R. R. Schmidt ◽  
K. P. Chepenik ◽  
B. V. Paynton
Keyword(s):  
Body Weight ◽  
Folic Acid ◽  
Total Body Weight ◽  
Pregnant Rats ◽  
Skeletal Malformations ◽  
Fetal Rat ◽  
Pteroylglutamic Acid ◽  
Limb Malformations ◽  
Total Body ◽  
Rate Of Accumulation

Pregnant rats were subjected to either a folic-acid-deficient regimen that produces multiple congenital skeletal malformations, or a control folic-acid-supplemented regimen. Fetal limbs were extirpated on days 16 and 18 of gestation, pooled from each litter, homogenized, and aliquots set aside for hydroxyproline, protein and DNA determinations. We found that (1) the amount of protein recovered per treated limb was approximately half that of controls on both days, (2) the amount of protein recovered per treated or controlday-18 limb was twice that of a day-16 limb, (3) treated limbs constituted the same percentage of total body weight as in controls on day 16, but a smaller percentage than in controls on day 18, and (4) the concentration of hydroxyproline (μg/mg protein) was significantly less for treated limbs than for controls on day 18 of gestation. We noted also that: (1) lowest hydroxyproline concentrations were found in limbs from treated fetuses with gross limb malformations, (2) intermediate concentrations were found in limbs of treated fetuses not exhibiting gross limb malformations, and (3) highest concentrations were found in control limbs. We suggest that the treatment resulted in (1) a decreased rate of accumulation of protein in limbs prior to day 16, but not from day 16 to day 18, (2) a decreased rate of accumulation of some non-protein component(s) in treated limbs from day 16 to day 18, and (3) an altered collagen metabolism.

scholarly journals Growth and body weight of free-range reindeer in western Alaska

Rangifer ◽  
2000 ◽  
Vol 20 (2-3) ◽  
pp. 221 ◽  
Author(s):  
Greg L. Finstad ◽  
Alexander K. Prichard
Keyword(s):  
Body Weight ◽  
Growth Rates ◽  
Total Body Weight ◽  
Growth Patterns ◽  
Spatial And Temporal Variation ◽  
Adult Males ◽  
Body Weights ◽  
Total Body ◽  
Reproductive Females ◽  
Average Body

Total body weight of 9749 reindeer calves and 4798 adult reindeer were measured from 1984 to 1999 on the Seward Peninsula, western Alaska, USA. Growth rates of male and female calves, and annual growth patterns of adults were determined. Male calves grew faster than female calves. Reproductive females were lighter than non-reproductive females during summer but there was no effect of reproduction on average body weights the following winter. Adult males age 3-5 were heavier during summer than winter. Castrated males weighed the same as uncastrated males in summer, but were significantly heavier in winter, and did not display the large annual fluctuations in weight typical of reproductive males and females. Growth rates were higher and body weights greater in this herd than many other cir-cumpolar reindeer populations. We suggest these kinds of physiological indices should be used to monitor the possible effects of spatial and temporal variation in population density and to evaluate changes in herding practices.

Sign in / Sign up

Export Citation Format

Share Document