scholarly journals Effects of Xuesaitong on the Pharmacokinetics of Losartan: An In Vivo UPLC-MS/MS Study

2019 ◽  
Vol 2019 ◽  
pp. 1-8
Author(s):  
Weina Ma ◽  
Lei Lv ◽  
Jungang Guo ◽  
Yongjun Meng ◽  
Yinghua Wang ◽  
...  
Keyword(s):  
Apparent Volume ◽  
Volume Of Distribution ◽  
Sprague Dawley ◽  
Oral Gavage ◽  
Sprague Dawley Rats ◽  
Liquid Chromatography Tandem Mass ◽  
Multiple Blood ◽  
Apparent Volume Of Distribution ◽  
Noncompartmental Model

The aim of this study was to examine whether Xuesaitong, a multiherbal formulation for coronary heart disease, alters the pharmacokinetics of losartan. Adult male Sprague Dawley rats randomly received losartan (10 mg/kg) or losartan plus Xuesaitong (10 mg/kg) through an oral gavage (n = 6). Multiple blood samples were obtained for up to 36 h to determine the concentrations of losartan and its active metabolite, EXP3174, through ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Pharmacokinetics were estimated using a noncompartmental model. The half-life (t1/2) of losartan was decreased by Xuesaitong (4.26 ± 1.51 vs. 6.35 ± 2.10 h; P<0.05). The apparent volume of distribution (Vd) of losartan was also decreased by the combination of losartan and Xuesaitong (4.41 ± 1.61 vs. 7.20 ± 2.41 mL; P<0.05). The time to maximum concentration (Tmax) of losartan was increased by Xuesaitong (1.06 ± 1.04 vs. 0.13 ± 0.05 h; P<0.05). Xuesaitong also decreased the t1/2 of EXP3174 (8.22 ± 1.41 vs. 6.29 ± 1.38 h; P<0.05). These results suggest that there is a complex interaction between losartan and Xuesaitong. In addition to enhanced elimination of losartan and EXP3174, Xuesaitong may also decrease the absorption rate and Vd of losartan.

Erythropoietin metabolism and pharmacokinetics in experimental nephrosis

1992 ◽  
Vol 263 (5) ◽  
pp. F812-F815 ◽  
Author(s):  
X. J. Zhou ◽  
N. D. Vaziri
Keyword(s):  
Nephrotic Syndrome ◽  
Apparent Volume ◽  
Volume Of Distribution ◽  
Control Group ◽  
Pharmacokinetic Studies ◽  
Sprague Dawley ◽  
Marked Rise ◽  
Metabolism Regulation ◽  
Sprague Dawley Rats ◽  
Apparent Volume Of Distribution

We studied erythropoietin (EPO) metabolism, regulation, and pharmacokinetics in rats with nephrotic syndrome. Sprague-Dawley rats were randomized into nephrotic (puromycin-induced) and pair-fed control groups. Animals were studied at baseline and after induction of anemia or exposure to hypobaric conditions (32 cmHg). The nephrotic group showed a reduced hematocrit (P < 0.05), a significant urinary EPO excretion, and an inappropriately low plasma EPO. Induction of anemia and exposure to hypoxia resulted in a less pronounced elevation of plasma EPO in the nephrotic group than in the control group (P < 0.05). The blunted plasma EPO response to hypoxia in nephrotic animals was associated with a marked rise in urinary EPO excretion. Pharmacokinetic studies following intravenous injection of recombinant EPO, 100 U/kg, revealed a shorter plasma half-life (t1/2) (P < 0.05), larger apparent volume of distribution (P < 0.05), and greater clearance (P < 0.02) in the nephrotic group than in the controls. Estimated endogenous EPO production rate in nephrotic rats with severe anemia was significantly lower (P < 0.05) than that of equally anemic controls. Thus puromycin-induced nephrotic syndrome is associated with marked urinary loss of EPO, relatively depressed plasma EPO response to anemia and hypoxia, as well as reduced plasma t1/2, increased volume of distribution, and clearance of exogenous EPO.

Toxicokinetic and Genotoxicity Study of NNK in Male Sprague-Dawley Rats Following Nose-Only Inhalation Exposure, Intraperitoneal Injection, and Oral Gavage

2021 ◽  
Author(s):  
Shu-Chieh Hu ◽  
Matthew S Bryant ◽  
Estatira Sepehr ◽  
Hyun-Ki Kang ◽  
Raul Trbojevich ◽  
...  
Keyword(s):  
Human Lung ◽  
Inhalation Exposure ◽  
Systemic Exposure ◽  
Sprague Dawley ◽  
Oral Gavage ◽  
Sd Rats ◽  
New Information ◽  
Sprague Dawley Rats ◽  
Tissue Specimens

Abstract The tobacco-specific nitrosamine NNK [4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone] is found in tobacco products and tobacco smoke. NNK is a potent genotoxin and human lung carcinogen; however, there are limited inhalation data for the toxicokinetics (TK) and genotoxicity of NNK in vivo. In the present study, a single dose of 5x10−5, 5x10−3, 0.1, or 50 mg/kg body weight (BW) of NNK, 75% propylene glycol (vehicle control), or air (sham control) was administered to male Sprague-Dawley (SD) rats (9-10 weeks age) via nose-only inhalation (INH) exposure for 1 hour. For comparison, the same doses of NNK were administered to male SD rats via intraperitoneal (IP) injection and oral gavage (PO). Plasma, urine, and tissue specimens were collected at designated timepoints and analyzed for levels of NNK and its major metabolite 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) and tissue levels of DNA adduct O6-methylguanine by LC/MS/MS. TK data analysis was performed using a non-linear regression program. For the genotoxicity subgroup, tissues were collected at 3 hours post-dosing for comet assay analysis. Overall, the TK data indicated that NNK was rapidly absorbed and metabolized extensively to NNAL after NNK administration via the three routes. The IP route had the greatest systemic exposure to NNK. NNK metabolism to NNAL appeared to be more efficient via INH than IP or PO. NNK induced significant increases in DNA damage in multiple tissues via the three routes. The results of this study provide new information and understanding of the toxicokinetics and genotoxicity of NNK.

Pharmacokinetics and Tissue Distribution of Norfloxacin in Eel Following Oral Gavage

2012 ◽  
Vol 452-453 ◽  
pp. 1069-1073
Author(s):  
Yun Hua Hui ◽  
You Qiong Cai ◽  
Bing Feng ◽  
Wen Ruan ◽  
Hui Juan Yu
Keyword(s):  
Apparent Volume ◽  
Volume Of Distribution ◽  
European Eel ◽  
Half Time ◽  
Oral Gavage ◽  
Concentration Time ◽  
Liver And Kidney ◽  
Apparent Volume Of Distribution ◽  
Different Tissues ◽  
Body Clearance

The pharmacokinetics of norfloxacin were investigated in the European eel after a single oral gavage of 10 mg norfloxacin per kg body weight. The concentrations of norfloxacin in the main tissues (kidney, muscle, hepatopancreas and blood) were simultaneously detected by HPLC. All of the concentration-time curves of norfloxacin in the plasma, muscle and liver were consistent with absorption of a two-compartment open kinetic model. Norfloxacin was widely distributed in different tissues in the European eel. Apparent volume of distribution (Vd) was 52.025 L/kg, 34.589 L/kg, 2.795 L/kg, and 0.969 L/kg, in plasma, muscle, liver and kidney, respectively. Norfloxacin in the eel was proved to eliminate slowly, and half-time (tβ1/2) in plasma, muscle, liver and kidney, was 201.222 h, 123.789 h, 120.634 h and 627473.495 h, respectively. Body clearance was 0.689 L / ( kg•h ), 1.793 L/( kg•h ), 0.097 L/( kg•h ) and 0.028 L /( kg•h ), in plasma, muscle, liver and kidney, respectively.

scholarly journals Quantification of [11C]yohimbine Binding to α2 Adrenoceptors in Rat Brain in vivo

2015 ◽  
Vol 35 (3) ◽  
pp. 501-511 ◽  
Author(s):  
Jenny-Ann Phan ◽  
Anne M Landau ◽  
Dean F Wong ◽  
Steen Jakobsen ◽  
Adjmal Nahimi ◽  
...  
Keyword(s):  
Rat Brain ◽  
Volume Of Distribution ◽  
Sprague Dawley ◽  
Logan Plot ◽  
Positron Emission ◽  
Amphetamine Administration ◽  
Sprague Dawley Rats ◽  
Extracellular Level ◽  
Arterial Plasma

We quantified the binding potentials ( BPND) of [11C]yohimbine binding in rat brain to alpha-2 adrenoceptors to evaluate [11C]yohimbine as an in vivo marker of noradrenergic neurotransmission and to examine its sensitivity to the level of noradrenaline. Dual [11C]yohimbine dynamic positron emission tomography (PET) recordings were applied to five Sprague Dawley rats at baseline, followed by acute amphetamine administration (2 mg/kg) to induce elevation of the endogenous level of noradrenaline. The volume of distribution ( VT) of [11C]yohimbine was obtained using Logan plot with arterial plasma input. Because alpha-2 adrenoceptors are distributed throughout the brain, the estimation of the BPND is complicated by the absence of an anatomic region of no displaceable binding. We used the Inhibition plot to acquire the reference volume, VND, from which we calculated the BPND. Acute pharmacological challenge with amphetamine induced a significant decline of [11C]yohimbine BPND of ∼38% in all volumes of interest. The BPND was greatest in the thalamus and striatum, followed in descending order by, frontal cortex, pons, and cerebellum. The experimental data demonstrate that [11C]yohimbine binding is sensitive to a challenge known to increase the extracellular level of noradrenaline, which can benefit future PET investigations of pathologic conditions related to disrupted noradrenergic neurotransmission.

The Pharmacokinetics of Buserelin after Intramuscular Administration in Pigs and Cows

2021 ◽  
Author(s):  
Zhengrong Gao ◽  
Yu Liu ◽  
Yuxin Yang ◽  
Yuying Cao ◽  
Jicheng Qiu ◽  
...  
Keyword(s):  
Area Under The Curve ◽  
Apparent Volume ◽  
Ultra Performance Liquid Chromatography ◽  
Volume Of Distribution ◽  
Pharmacokinetic Parameters ◽  
Maximum Plasma ◽  
Elimination Half ◽  
Liquid Chromatography Tandem Mass ◽  
Stability Method ◽  
Apparent Volume Of Distribution

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.

Metabolism and influence of gastrin-52 on gastric acid secretion in humans

1995 ◽  
Vol 269 (4) ◽  
pp. G600-G605 ◽  
Author(s):  
C. P. Hansen ◽  
F. Stadil ◽  
J. F. Rehfeld
Keyword(s):  
Acid Secretion ◽  
Gastric Acid Secretion ◽  
Gastric Acid ◽  
Normal Subjects ◽  
Apparent Volume ◽  
Volume Of Distribution ◽  
Gel Chromatography ◽  
A Minor ◽  
Apparent Volume Of Distribution

It has been shown recently that the two largest alpha-carboxyamidated progastrin products are gastrin-71 and gastrin-52. Human gastrin-52 has now been synthesized, and the effect on gastric acid secretion and elimination from plasma was examined and compared with gastrin-17 in 12 normal subjects. The peptides were infused separately in four consecutive doses; the maximum response of gastrin-17 and gastrin-52 was 25.2 +/- 2.8 and 22.2 +/- 2.8 mmol H+/50 min, respectively (P< 0.01). This difference in efficacy was presumably related to nonequilibrium of gastrin-52 between plasma and receptor. The elimination of gastrin-17 was monoexponential with a half-life of 4.7 +/- 0.3 min; clearance and apparent volume of distribution were 16.7 +/- 1.5 ml.kg-1.min-1 and 106.0 +/- 9.2 ml/kg, respectively. The elimination of gastrin-52 was biexponential, the half-lives were 4.9 +/- 0.7 and 49.9 +/- 4.2 min, and clearance and apparent volume of distribution were 1.9 +/- 0.2 ml.kg-1.min-1 and 106.3 +/- 10.1 ml/kg, respectively. Gel chromatography of plasma samples drawn during infusion of gastrin-52 revealed that most of the immunoreactivity eluted in the position of the intact peptide. Small peaks in the positions of gastrin-34 and the NH2-terminal pentapeptide fragment of gastrin-52 indicate that a minor part of gastrin-52 is degraded to smaller peptides in vivo. It is concluded that gastrin-52 is bioactive with an efficacy close to or similar to that of gastrin-17. A minor fraction of gastrin-52 undergoes postsecretory cleavage either in plasma or after capillary transit.

scholarly journals Pharmacological comparison of four biopolymeric natural gums as hemostatic agents for management of bleeding wounds: preliminary in vitro and in vivo results

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Himanshu Kushwah ◽  
Nidhi Sandal ◽  
Meenakshi Chauhan ◽  
Gaurav Mittal
Keyword(s):  
Xanthan Gum ◽  
Guar Gum ◽  
Human Lymphocytes ◽  
Sprague Dawley ◽  
Gum Tragacanth ◽  
Civilian Trauma ◽  
Sprague Dawley Rats ◽  
Cytotoxicity Studies

Abstract Background Uncontrolled bleeding is one of the primary reasons for preventable death in both civilian trauma and military battle field. This study evaluates in vitro and in vivo hemostatic potential of four biopolymeric natural gums, namely, gum tragacanth, guar gum, xanthan gum, and gum acacia. In vitro evaluation of whole blood clotting time and erythrocyte agglutination assay were carried out. In vitro cytotoxicity studies with respect to each gum were done in human lymphocytes to ascertain percent cell viability. In vivo hemostatic potential of each gum (as sponge dressing and powder form) was evaluated in Sprague Dawley rats using tail bleeding assay and compared with commercially available hemostatic sponge. Other important parameters like (a) time taken for complete hemostasis, (b) amount of blood absorbed, (c) adherence strength of developed hemostatic dressing(s), (d) incidence of re-bleeding, and (e) survival of animals were also studied. Results Of the four test gums studied, xanthan gum (@3mg/ml of blood) and gum tragacanth (@35mg/ml of blood) were able to clot blood in least time (58.75±6.408 s and 59.00±2.082 s, respectively) and exhibited very good hemostatic potential in vitro. Except for xanthan gum, all other test gums did not exhibit any significant cytotoxicity at different time points till 24 h. In rat tail bleeding experiments, gum tragacanth sponge dressing and powder achieved hemostasis in least time (156.2±12.86 s and 76±12.55 s, respectively) and much earlier than commercially available product (333.3±38.84 s; p˂0.01). Conclusion Results indicate potential of gum tragacanth to be developed into a suitable hemostatic product.

Bioavailability in Vivo of Benzo[a]Pyrene Adsorbed to Diesel Particulate

1991 ◽  
Vol 7 (3) ◽  
pp. 125-139 ◽  
Author(s):  
David R. Bevan ◽  
David M. Ruggio
Keyword(s):  
Health Risks ◽  
Quantitative Description ◽  
Intratracheal Instillation ◽  
Direct Analysis ◽  
Sprague Dawley ◽  
Reasonable Estimate ◽  
Diesel Particulate ◽  
Sprague Dawley Rats

To evaluate health risks associated with exposure to particulates in the environment, it is necessary to quantify the bioavailability of carcinogens associated with the particulates. Direct analysis of bioavailability in vivo is most readily accomplished by adsorbing a radiolabeled form of the carcinogen to the particulate. A sam ple of native diesel particulate collected from an Oldsmobile die sel engine that contained 1.03 μ g benzo[ a] pyrene ( BaP)/ g particulate was supplemented with exogenous [ 3 H]- BaP to pro duce a particulate containing 2.62 μ g BaP/g. To insure that elu tion of BaP from native and [3 H] -BaP-supplemented particulate was similar, in vitro analyses were performed. When using phos pholipid vesicles composed of dimyristoylphosphatidylcholine (DMPC), 1.52% of total BaP was eluted from native particulate into the vesicles in 18 hrs; from [ 3 H] -BaP supplemented particu late, 1.68% was eluted. Using toluene as eluent, 2.55% was eluted from native particulate, and 8.25% from supplemented particulate, in 6 hrs. Supplemented particulate was then instilled intratracheally into male Sprague-Dawley rats and distribution of radioactivity was analyzed at selected times over 3 days. About 50% of radioactivity remained in lungs at 3 days following instil lation, with 30% being excreted into feces and the remainder dis tributed throughout the organs of the rats. To estimate the amount of radioactivity that entered feces through swallowing of a portion of the instilled dose, [3 H] -BaP-supplemented particu late was instilled intratracheally into rats that had a cannula sur gically implanted in the bile duct. Rate of elimination of radio activity into bile was monitored; 10.6% of radioactivity was re covered in 6 hr, an amount slightly lower than the 12.8% ex creted in 6 hrs into feces of animals with intact bile ducts. Our studies provide a quantitative description of the distribution of BaP and its metabolites following intratracheal instillation of diesel particulate. Because rates of elution of BaP in vitro are similar for native diesel particulate and particulate with supple mental [ 3H] -BaP, our results provide a reasonable estimate of the bioavailability in vivo of BaP associated with diesel particu late.

scholarly journals The in vivo Pig-a gene mutation assay is applied to study the genotoxicity of procarbazine hydrochloride in Sprague-Dawley rats

2016 ◽  
Vol 3 (4) ◽  
pp. 167-175 ◽  
Author(s):  
Jiang Pu ◽  
Yuanyuan Deng ◽  
Xiaoyan Tan ◽  
Gaofeng Chen ◽  
Cong Zhu ◽  
...  
Keyword(s):  
Gene Mutation ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Mutation Assay ◽  
Gene Mutation Assay
Sign in / Sign up

Export Citation Format

Share Document