scholarly journals Pharmacokinetic Study of Modafinil in Relation to Gender and Ethnicity in Healthy Young Chinese Volunteers

2010 ◽  
Vol 13 (3) ◽  
pp. 443 ◽  
Author(s):  
Tao Guo ◽  
Longshan Zhao ◽  
Dong-Ya Xia

Purpose. The pharmacokinetics of modafinil were investigated in relation to gender and ethnicity in healthy young volunteers from Han, Mongolian, Korean, Uygur and Hui ( n = 10/group) following administration of a single 200 mg oral dose. Methods. Blood samples were collected over 48 h for the determination of plasma levels of modafinil and its acid metabolite by High performance liquid chromatography with an ultraviolet detector. Pharmacokinetic parameters were evaluated using noncompartmental methods. Results. Modafinil was well tolerated and safe at a single oral dose of 200 mg. All participants reported adverse events, none of which was serious or unexpected. The maximum plasma concentration (Cmax) and area under the curve for modafinil concentration versus time, which was extrapolated to infinity (AUC0-∞), were higher in women compared to men (p < 0.01). No gender-based difference was noted in the total body weight-normalized modafinil oral clearance. The total body weight-normalized modafinil apparent volume of distribution and the t1/2 was found to exhibit an ethnicity-based significant difference. Conclusion. The results of the current study suggest that there might be pharmacokinetic differences related to gender and ethnicity in the pharmacokinetics of modafinil.

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Moreno Zanardo ◽  
Fabio Martino Doniselli ◽  
Anastassia Esseridou ◽  
Massimiliano Agrò ◽  
Nicol Antonina Rita Panarisi ◽  
...  

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.


Author(s):  
Ryan D Dunn ◽  
Ryan L Crass ◽  
Joseph Hong ◽  
Manjunath P Pai ◽  
Lynne C Krop

Abstract Purpose To compare methods of estimating vancomycin volume of distribution (V) in adults with class III obesity. Methods A retrospective, multicenter pharmacokinetic analysis of adults treated with vancomycin and monitored through measurement of peak and trough concentrations was performed. Individual pharmacokinetic parameter estimates were obtained via maximum a posteriori Bayesian analysis. The relationship between V and body weight was assessed using linear regression. Mean bias and root-mean-square error (RMSE) were calculated to assess the precision of multiple methods of estimating V. Results Of 241 patients included in the study sample, 159 (66.0%) had a BMI of 40.0–49.9 kg/m2, and 82 (34.0%) had a BMI of ≥50.0 kg/m2. The median (5th, 95th percentile) weight of patients was 136 (103, 204) kg, and baseline characteristics were similar between BMI groups. The mean ± S.D. V was lower in patients with a BMI of 40.0–49.9 kg/m2 than in those with a BMI of ≥50.0 kg/m2 (72.4 ± 19.6 L versus 79.3 ± 20.6 L, p = 0.009); however, body size poorly predicted V in regression analyses (R2 < 0.20). A fixed estimate of V (75 L) or use of 0.52 L/kg by total body weight yielded similar bias and error in this population. Conclusion Results of the largest analysis of vancomycin V in class III obesity to date indicated that use of a fixed V value (75 L) and use of a TBW-based estimate (0.52 L/kg) for estimation of vancomycin V in patients with a BMI of ≥40.0 kg/m2 have similar bias. Two postdistribution vancomycin concentrations are needed to accurately determine patient-specific pharmacokinetic parameters, estimate AUC, and improve the precision of vancomycin dosing in this patient population.


2001 ◽  
Vol 45 (2) ◽  
pp. 596-600 ◽  
Author(s):  
Andreas H. Groll ◽  
Bryan M. Gullick ◽  
Ruta Petraitiene ◽  
Vidmantas Petraitis ◽  
Myrna Candelario ◽  
...  

ABSTRACT The pharmacokinetics of the antifungal echinocandin-lipopeptide caspofungin (MK-0991) in plasma were studied in groups of three healthy rabbits after single and multiple daily intravenous administration of doses of 1, 3, and 6 mg/kg of body weight. Concentrations were measured by a validated high-performance liquid chromatography method and fitted into a three-compartment open pharmacokinetic model. Across the investigated dosage range, caspofungin displayed dose-independent pharmacokinetics. Following administration over 7 days, the mean peak concentration in plasma (C max) ± standard error of the mean increased from 16.01 ± 0.61 μg/ml at the 1-mg/kg dose to 105.52 ± 8.92 μg/ml at the 6-mg/kg dose; the mean area under the curve from 0 h to infinity rose from 13.15 ± 2.37 to 158.43 ± 15.58 μg · h/ml, respectively. The mean apparent volume of distribution at steady state (Vdss) was 0.299 ± 0.011 liter/kg at the 1-mg/kg dose and 0.351 ± 0.016 liter/kg at the 6-mg/kg dose (not significant [NS]). Clearance (CL) ranged from 0.086 ± 0.017 liter/kg/h at the 1-mg/kg dose to 0.043 ± 0.004 liter/kg/h at the 6-mg/kg dose (NS), and the mean terminal half-life was between 30 and 34 h (NS). Except for a trend towards an increasedVdss, there were no significant differences in pharmacokinetic parameters in comparison to those after single-dose administration. Caspofungin was well tolerated, displayed linear pharmacokinetics that fit into a three-compartment pharmacokinetic model, and achieved sustained concentrations in plasma that were multiple times in excess of reported MICs for susceptible opportunistic fungi.


2020 ◽  
Vol 79 (OCE2) ◽  
Author(s):  
Fathimath Naseer ◽  
Ruth Price ◽  
Adele McElroy ◽  
Carel Le Roux ◽  
Tamsyn Redpath ◽  
...  

AbstractBariatric surgery, including Gastric Bypass (GBP) Surgery, is the most efficient modality to manage severe obesity. Resting Energy Expenditure (REE) is an area of interest in the context of weight loss (WL) as it has been postulated to be an independent predictor of WL success following GBP. As such, the aim of this study is to investigate the impact of REE on WL following GBP. 31 GBP patients (77.4% females BMI 45.5 ± 7.0kg/m2 ; 47.3 ± 11.6y) and 32 weight-stable controls (46.9% females; BMI 27.0 ± 4.6kg/m2 ; 41.1 ± 13.5y) were assessed at one-month pre-surgery and at 3 and 12-months post-surgery. Fat mass (FM) and fat-free mass (FFM) were measured using dual energy X-ray absorptiometry (Lunar iDXA, GE Healthcare). REE was measured under standardised conditions using indirect calorimetry (ECAL, Metabolic Health Solutions). Statistical analyses were performed with SPSS v24.0, Armonk, NY. Multiple regression analysis showed that FM (P = 0.001), FFM (P < 0.0001) and gender (P = 0.012) significantly predicted the interindividual variability in REE. Total body weight (TBW) was removed from the model due to collinearity. Adjusted-REE values were then generated using the above predictor variables. Low-REE and high-REE groups were created using within-group adjusted-REE split. At both follow-ups (3- and 12-months post-surgery), patients had a greater reduction in TBW, FM, FFM, measured-REE and adjusted-REE values compared with controls (P < 0.0001). There was also no significant difference between measured and adjusted-REE values at all time-points (P > 0.05). Patients with high REEs at baseline lost more TBW than those in the low-REE group at 3-months post-surgery (-24.9 ± 6.5 kg vs. -16.6 ± 7.0 kg; P = 0.005) and 12-months post-surgery (-41.3 ± 12.5 kg vs. -25.8 ± 10.4.0 kg; P = 0.003). There was no significant difference in mean TBW changes for controls in the low-and high-REE groups at both follow-ups. Patients with high REEs at 3-months post-surgery did not lose more TBW than those in the low-REE group at 12-months post-surgery (-30.1 ± 12.8 kg vs. -38.6 ± 14.4 kg; P = 0.155). Similarly, there was no difference in mean TBW reduction between controls in the low- and high-REE groups (P = 0.115). Thus while patients with a high adjusted-REE value at baseline (> 9746.6kJ/day) lost more weight at 3- and 12-months post-GBP, it is plausible that from the third to the 12th month post-surgery, other key drivers of weight loss, particularly the reduction in energy intake are more important in predicting WL. Further research with a larger sample size is required to increase the chances of detecting a true effect.


1970 ◽  
Vol 6 (1) ◽  
pp. 93-97
Author(s):  
MS Islam ◽  
MMH Sikder ◽  
MA Awal ◽  
M Mostofa ◽  
AA Trisha

The study was carried out to determine the biodisposition kinetics of ciprofloxacin in sheep model in Department of Pharmacology, Bangladesh Agricultural University. Healthy sheep of both sexes (n=65) were divided into 13 groups, each consists of five and given a single dose of ciprofloxacin @ 5 mg/kg bwt intramuscularly .Blood sample was collected from each group of sheep at 0, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 10 and 12 hours interval respectively. Serum concentration of ciprofloxacin was determined by spectrophotometric method. The pharmacokinetic parameters were measured by single compartment open model and first order kinetics. The peak concentration of ciprofloxacin was 3.56±0.15mg/ ml, absorption half-life and biological half-life were 0.0846±1.79 and 1.75±0.15 h respectively. The apparent volume of distribution was found 35.54 mg/liter. The absorption rate constant was 8.188h-1, MRT was 2.647h-1 and total body clearances were found 16.88 h-1. These result suggested that a dose of 5 mg/kg bwt provides maximum plasma concentration and is effective in the control of many infectious diseases of sheep. Key words: Plasma pharmacokinetics, ciprofloxacin, sheep DOI = 10.3329/bjvm.v6i1.1344 Bangl. J. Vet. Med. (2008). 6 (1): 93-97


2020 ◽  
Vol 13 (1) ◽  
pp. 50-58
Author(s):  
Taha AL-Sharqi ◽  
Majid Abdullah

This study aimed to investigate the effect of wool shearing and the environmental factors represented by some hot months of the year (July August and September) on some production characteristics in Turkish Awassi ewes. 18 ewes, aged 3-5 years, with an average weight of about 55±1.43 kg, were used. The ewes divided into three treatments. The first group control (T1) were not shorned the wool, the second group (T2) wool of ewes were sheared at a distance of 1 cm from skin, while third group (T3) wool of ewes were sheared at level of the skin. The value of the weekly Temperature-humidity index THI in this study (32.33, 31.08, 31.70, 32.53, 33.45, 33.83, 34.60, 33.91, 31.90, 31.10, 31.84, 32.74) weeks respectively, while the monthly THI was (31.63, 33.48, 31.82) months of the study in July August and September in a respectively. The results showed a significant difference (p<0.05) between the treatments in body weight that were recorded at the tenth week where the THI reached. While the Second group recorded (2.16 ± 0.802) kg compared to T1, T3 (0.916 ± 0.723) (0.583 ± 0.490) kg respectively. While the total body weight of ewes and birth weight showed non-significant differences between different treated groups. From another hand the result showed non-significant differences feed and significant differences in water consumption between different treated groups. From the current study concluded that the level of shearing wool in Turkish Awassi ewes in conjunction with high temperature has an effect in production characteristics by reducing the effect of heat stress on the ewes.


Author(s):  
G. Rajkumar ◽  
M. T. Dipu ◽  
K. Lalu ◽  
K. Shyama ◽  
P. S. Banakar

An experiment was conducted to evaluate the effect of maize green fodder produced by hydroponics system on the performance of eighteen weaned crossbred calves and Calves were divided into three groups T1, T2 and T3 of six each as uniformly. The calf starter in dietary treatments T1, T2 and T3 contained 24, 20 and 17 per cent of Crude Protein (CP), respectively and 70 per cent Total Digestible Nutrients (TDN). The T2 and T3 treatments were made iso-nitrogenous with T1 by supplementing hydroponics maize fodder. The results obtained in the present study showed significant difference among different treatment groups regarding Dry matter intake (DM), total body weight gain, Average daily gain (ADG) and Feed conversion ratio (FCR) with a higher (P less than 0.05) values observed for calves belonging to T3 than groups T1 and T2. Data on digestibility of nutrients does not reveal any difference (P>0.05) among treatment groups. Cost per kg gain was significantly (P less than 0.05) lower in T3 (Rs.102.14) than groups T2 (Rs. 111.64) and T1 (Rs. 119.82). On conclusion, feeding of hydroponics maize fodder as a partial feed substitute of calf starter on protein basis at seven per cent level improves the DM intake, total body weight gain, ADG and lowers the cost per kg body weight gain.


1988 ◽  
Vol 6 (8) ◽  
pp. 1321-1327 ◽  
Author(s):  
K A Rodvold ◽  
D A Rushing ◽  
D A Tewksbury

A study was carried out to examine the effect, if any, of obesity on doxorubicin pharmacokinetics. Body weight was found to be significantly related to doxorubicin clearance (r = -.75; P less than .001) and elimination half-life (r = .62; P = .003). Thus, the contribution of obesity on pharmacokinetics of antineoplastic agents should be taken into consideration in the analysis of clinical data with respect to toxicity and tumor response. Twenty-one patients were studied with their first course of doxorubicin (50 to 70 mg/m2) administered as a 60-minute intravenous (IV) infusion. Patients were divided into three groups on the basis of percentage of ideal body weight (IBW): normal (less than 115% IBW), mildly obese (115% to 130% IBW), and obese (greater than 130% IBW). Blood samples were collected up to 48 hours after the infusion and analyzed for doxorubicin and its metabolite, doxorubicinol, by high performance liquid chromatography. Doxorubicin area under the curve (AUC) was greater in obese than in normal patients (2,209 v 1,190 ng h/mL; P less than .05), yielding correspondingly reduced systemic clearance of the agent in obese patients (891 v 1,569 mL/min; P less than .001). The mean elimination half-life (T1/2) was 20.4 hours in the obese patients and 13.0 hours in the normal patients. The apparent volume of distribution (Vss) was not significantly different among the three groups of patients, indicating that the prolonged T1/2 in the obese patients is due to the reduction in clearance. The AUC and T1/2 of doxorubicinol were similar among all patient groups.


1970 ◽  
Vol 38 (1-2) ◽  
pp. 102-107 ◽  
Author(s):  
AKM Masum ◽  
MN Islam ◽  
MAS Khan

An experiment was conducted to study the utilization of soymilk as milk replacer for raising calves. Nine crossbred calves were selected and divided into three groups on the basis of their body weight and genotype. The calves of group A were reared by cow milk, group B reared by strained soymilk and group C reared by unstrained soymilk. It was found that, total body weight gain of group A, B and C were 13.933 ± 1.222, 13.800 ± 0.917 and 13.233 ± 1.537 Kg, respectively. There was no significant difference among the three groups of calves. Non-significant differences were also seen for increment in wither height (5.588 ± 0.508, 5.419 ± 0.529 and 5.080 ± 0.440 cm, respectively), length (6.096 ± 0.440, 5.927 ± 0.388 and 5.503 ± 0.388 cm, respectively) and heart-girth (5.842 ± 0.440, 5.588 ± 0.916 and 5.419 ± 0.388 cm, respectively) of calves. Economic analysis showed that soymilk was cheaper than cow milk (Tk. 8.0 vs Tk. 44.0). It can be concluded that soymilk as milk replacer could be used successfully for raising dairy calves. DOI: http://dx.doi.org/10.3329/bjas.v38i1-2.9918 BJAS 2009; 38(1-2): 102-107


2021 ◽  
Author(s):  
Zhengrong Gao ◽  
Yu Liu ◽  
Yuxin Yang ◽  
Yuying Cao ◽  
Jicheng Qiu ◽  
...  

Abstract Background: Buserelin is a LHRH agonist used for the treatment of hormone-dependent diseases in males and females. However, the pharmacokinetics of buserelin in pigs and cows are not clearly understood. This study was designed to develop a sensitive method to determine the concentration of buserelin and to investigate the pharmacokinetic parameters after intramuscular (i.m.) administration in pigs and cows. Results: A sensitive and rapid stability method based on ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) was developed. The pharmacokinetic parameters of buserelin after i.m. administration were studies in five pigs and five cows at a single dose of 1 mg per pig and 3 mg per cow. The plasma kinetics were analyzed by WinNonlin 8.1.0 software using a non-compartmental model. The mean concentration area under the curve (AUC0-t) was 25.02 ± 6.93 h·ng/mL for pigs and 5.63 ±1.86 h·ng/mL for cows. The maximum plasma concentration (Cmax) and time to reach the maximum concentration (tmax) were 10.99 ± 2.04 ng/mL and 0.57 ± 0.18 h for pigs and 2.68 ± 0.36 ng/mL and 1.05 ±0.27 h for cows, respectively. The apparent volume of distribution (Vz) in pigs and cows was 80.49 ± 43.88 L and 839.88 ± 174.77 L, respectively. The elimination half-time (t1/2λz), and clearance (CL) were 1.29 ± 0.40 h and 41.15 ± 11.18 L/h for pigs and 1.13 ± 0.3 h and 545.04 ± 166.40 L/h for cows, respectively. No adverse effects were observed in any of the animals. Conclusion: This study extends previous studies describing the pharmacokinetics of buserelin following i.m. administration in pigs and cows. Further studies investigating other factors were needed to establish therapeutic protocol in pigs and cows and to extrapolate these parameters to others economic animals.


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