Pharmacokinetics of Moxifloxacin in A 5/6th Nephrectomized Rat Model

1970 ◽  
Vol 2 (4) ◽  
pp. 748-755
Author(s):  
Hariprasath Kothandam ◽  
Venkatesh Palaniyappan ◽  
Sudheer Babu Idpuganti ◽  
Umamaheswari Muthusamy
Keyword(s):  
Renal Failure ◽  
Rat Model ◽  
Peak Plasma ◽  
Peak Plasma Concentration ◽  
Area Under The Curve ◽  
Laboratory Animals ◽  
Pharmacokinetic Parameters ◽  
Control Group ◽  
Significant Difference ◽  
And Control

Moxifloxacin (MFLX) is a new 8-methoxyfluoroquinolone derivative with a broad spectrum of antibacterial activity. MFLX at doses of 200 and 400 mg was selected to conduct the pharmacokinetic study and the drug was given orally to control and nephrectomized rats. A 5/6th nephrectomized rat model was used in this study. The drug levels in the plasma were determined using a spectrofluorimetric assay. The pharmacokinetic parameters viz. peak plasma concentration (Cmax) and area under the curve (AUC0-8) of the nephrectomized and control rats were compared. The Cmax for both 200 and 400 mg dose of MFLX in nephrectomized rats showed significant difference(P<0.001) from the control group, which reveals the changes in the Cmax of MFLX in renal failure. The AUC0-8 for both 200 and 400 mg dose of MFLX in nephrectomized rats differ significantly (P<0.001) from sham operated control group, which implies the variation in MFLX availability in altered renal function. The AUC0-8 for 400 mg dose of MFLX in nephrectomized rats differ significantly from 200 mg dose of MFLX in nephrectomized group, which reveals that in higher dose, MFLX shows an abrupt increase in the drug availability in renal failure. It is conclude that preclinical drug monitoring of moxifloxacin in laboratory animals can be performed by using 5/6th nephrectomized rat models for determining the dose of MFLX for kidney failured patients. Various pharmacokinetic parameters determined differed in nephrectomised rats when compared to the control.

scholarly journals Emulsification by TPGS or Quillaja Extract Increased Absorption and Affected Metabolism of Berberine in Humans

2021 ◽  
Vol 5 (Supplement_2) ◽  
pp. 381-381
Author(s):  
Yavuz Yagiz ◽  
Gary Wang ◽  
Liwei Gu
Keyword(s):  
Peak Plasma ◽  
Peak Plasma Concentration ◽  
Area Under The Curve ◽  
Total Content ◽  
Compartment Model ◽  
Analysis Of Covariance ◽  
High Tech ◽  
Pharmacokinetic Parameters ◽  
Funding Sources ◽  
Human Volunteers

Abstract Objectives Berberine is a botanical alkaloid used widely for the prevention of several diseases. However, the absorption rate of berberine is less than 1% in human. The objectives of this study were to determine whether emulsification by TPGS or Quillaja extract affect the absorption and metabolism of orally ingested berberine in human volunteers. Methods Twelve healthy subjects (7 male and 5 females, 21–50-year-old) participated this study. Each subject received 800 mg berberine in a powder form or emulsified with TPGS or Quillaja extract using a randomized crossover design with one-week washout period. Blood samples were collected at 0, 0.5, 1, 2, 3, 4, 6, 8, and 12 hours after dose. Plasma was hydrolyzed with glucuronidase and sulfatase before total content of berberine and its metabolites were analyzed on LC/MS/MS. Free forms of metabolites were determined in plasma without hydrolysis. Pharmacokinetic parameters were calculated using a non-compartment model before they were compared by analysis of covariance. Results The area under the curve (AUC) and peak plasma concentration (Cmax) of berberine was 6.6 μM.hr and 0.9 μM in participants received berberine powder. They were increased to 18.3 μM.hr and 4.5 μM by TPGS emulsification and 28 μM.hr and 5.1 μM by Quillaja extract emulsification, respectively. Berberrubine and demethylberberine were major metabolites of berberine. The AUC of free Berberrubine and demethylberberine was increased by 1.9 fold and 1.6 fold by TPGS and 5.9 folds and 2.7 folds by Quillaja extract, respectively, compared to berberine powder. Participants received berberine powder had AUC of 254 μM.hr and Cmax of 33 μM for total berberrubine. TPGS emulsification increased these values to 425 μM.hr and 54 μM, while Quillaja extract increased them to 341 μM.hr and 44 μM, respectively. Significant increases of AUC and Cmax were also observed for total demethylberberine by TPGS or Quillaja extract emulsification. Conclusions Emulsification of berberine with TPGS or Quillaja extract significantly increased the absorption of berberine and its metabolites in human compared to berberine supplement without emulsifiers. Funding Sources Florida High Tech Corridor Council and Designs for Health.

scholarly journals The effects of oral administration of Cola nitida on the pharmacokinetic profile of metoclopramide in rabbits

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Cecilia Nwadiuto Amadi ◽  
Wisdom Izuchukwu Nwachukwu
Keyword(s):  
Drug Interaction ◽  
Plasma Concentration ◽  
Oral Administration ◽  
Peak Plasma ◽  
Peak Plasma Concentration ◽  
Elimination Rate ◽  
Area Under The Curve ◽  
Pharmacokinetic Profile ◽  
Pharmacokinetic Parameters ◽  
Cola Nitida

Abstract Background Cola nitida is commonly chewed in many West African cultures to ease hunger pangs and sometimes for their stimulant and euphoriant qualities. Metoclopramide is a known substrate for P-gp, SULT2A1 and CYP2D6 and studies have revealed that caffeine- a major component of Cola nitida can induce P-glycoprotein (P-gp), SULT2A1 and SULT1A1, hence a possible drug interaction may occur on co-administration. The aim of this study was to investigate the pharmacokinetic interactions of Cola nitida and metoclopramide in rabbits. Methods The study was performed in two stages using five healthy male rabbits with a 1-week washout period between treatments. Stage one involved oral administration of metoclopramide (0.5 mg/kg) alone while in the second stage, metoclopramide (0.5 mg/kg) was administered concurrently with Cola nitida (0.7 mg/kg). Blood samples were collected after each stage at predetermined intervals and analyzed for plasma metoclopramide concentration using HPLC. Results Compared with control, the metoclopramide/Cola nitida co-administration produced a decrease in plasma concentration of metoclopramide at all the time intervals except at the 7th hour. The following pharmacokinetic parameters were also decreased: area under the curve (51%), peak plasma concentration (39%), half-life (51%); while an increase in elimination rate constant (113%) and clearance rate (98%) were noted indicating rapid elimination of the drug. A minimal decrease in absorption rate (10%) was also observed. Conclusions The results of this study reveal a possible herb-drug interaction between Cola nitida and metoclopramide.

scholarly journals ALTERATION OF PHARMACOKINETIC PARAMETERS OF PENTOXIFYLLINE USING NATURAL MUCOADHESIVE POLYMERS

2019 ◽  
pp. 153-157
Author(s):  
GNANASEKARAN JOHN SELVARAJ ◽  
ARUL BALASUBRAMANIAN ◽  
KOTHAI RAMALINGAM
Keyword(s):  
Drug Concentration ◽  
Peak Plasma ◽  
Peak Plasma Concentration ◽  
Fold Increase ◽  
Ocimum Basilicum ◽  
Plasma Drug Concentration ◽  
Pharmacokinetic Parameters ◽  
Plasma Drug ◽  
Time Curve ◽  
Significant Difference

Objective: The present study was aimed to alter the pharmacokinetic parameters of the drug pentoxifylline using a novel natural mucoadhesive polymer from two different plants, Manilkara zapotta Linn and Ocimum basilicum Linn. Methods: The polymer was isolated and six batches of mucoadhesive tablets of pentoxifylline was formulated with 3 different concentrations of each polymer. The best formulation from each of the polymer was selected and administered to rabbits and the plasma drug concentration was compared with the marketed formulation. The pharmacokinetic parameters such as such as Cmax, tmax, AUC, AUMC, λz, t1/2, and MRT were determined. Results: The plasma drug concentration vs time curve shows the extended-release of pentoxifylline when compared with the conventional marketed formulation. The results show that there is no change in the peak plasma concentration, but the significant difference was observed in t½, which showed approximately 2.5 fold increase from 2.44 to 6.87 h and the AUC showed five-fold increase from 22.40 to 117.19 μg*h/ml, and other pharmacokinetic parameters, when compared with the marketed formulation. Conclusion: The isolated polymer from the plants Manilkara zapotta Linn. and Ocimum basilicum Linn can be used as a carrier for developing mucoadhesive formulations and it alter the pharmacokinetic of pentoxifylline positively.

scholarly journals Activity of Tedizolid in Methicillin-Resistant Staphylococcus aureus Experimental Foreign Body-Associated Osteomyelitis

2016 ◽  
Vol 60 (11) ◽  
pp. 6568-6572 ◽  
Author(s):  
Kyung-Hwa Park ◽  
Kerryl E. Greenwood-Quaintance ◽  
Jayawant Mandrekar ◽  
Robin Patel
Keyword(s):  
Staphylococcus Aureus ◽  
Foreign Body ◽  
Rat Model ◽  
Peak Plasma ◽  
Peak Plasma Concentration ◽  
Intraperitoneal Administration ◽  
Control Group ◽  
Methicillin Resistant ◽  
Trough Concentrations ◽  
Rifampin Resistance

ABSTRACTWe compared tedizolid alone and tedizolid with rifampin to rifampin and vancomycin plus rifampin in a rat model of methicillin-resistantStaphylococcus aureus(MRSA) foreign body-associated osteomyelitis. The study strain was a prosthetic joint infection-associated isolate. Steady-state pharmacokinetics for intraperitoneal administration of tedizolid, vancomycin, and rifampin were determined in uninfected rats. MRSA was inoculated into the proximal tibia, and a wire was implanted. Four weeks later, the rats were treated intraperitoneally for 21 days with tedizolid (n= 14), tedizolid plus rifampin (n= 11), rifampin (n= 16), or vancomycin plus rifampin (n= 13). Seventeen rats received no treatment. After treatment, quantitative bone cultures were performed. Blood was obtained for determination of drug trough concentrations in the tedizolid and tedizolid plus rifampin groups. The mean peak plasma concentration and mean area under the concentration-time curve from time zero to 24 h for tedizolid were 12 μg/ml and 60 μg · h/ml, respectively. The bacterial loads in all treatment groups were significantly lower than those in the control group; those in the tedizolid- plus rifampin-treated animals were not significantly different from those in the vancomycin- plus rifampin-treated animals. The range of mean plasma trough concentrations in the tedizolid group was 0.44 to 0.73 μg/ml. Although neither tedizolid nor vancomycin resistance was detected in isolates recovered from bones, rifampin resistance was detected in 10 animals (63%) in the rifampin group, 8 animals (73%) in the tedizolid plus rifampin group, and a single animal (8%) in the vancomycin plus rifampin group. Tedizolid alone or tedizolid combined with rifampin was active in a rat model of MRSA foreign body-associated osteomyelitis. The emergence of rifampin resistance was noted in animals receiving tedizolid plus rifampin.

Modelling Dermal Pharmacokinetics Using in vitro Data. Part II. Fluazifop-butyl in Man

1993 ◽  
Vol 12 (3) ◽  
pp. 207-213 ◽  
Author(s):  
T.R. Auton ◽  
J.D. Ramsey ◽  
B.H. Woollen
Keyword(s):  
Risk Assessment ◽  
Peak Plasma ◽  
Peak Plasma Concentration ◽  
Area Under The Curve ◽  
Dermal Absorption ◽  
Pharmacokinetic Parameters ◽  
Oral Dosing ◽  
In Vitro Measurements ◽  
Model Predictions

In a previous paper it was demonstrated that dermal absorption of the herbicide fluazifop-butyl in the rat could be modelled by combining a knowledge of the pharmacokinetics following intravenous and oral dosing with in vitro measurements of dermal absorption. This paper demonstrates the validation of a similar model for the dermal absorption of fluazifop-butyl in man. Pharmacokinetic parameters derived from an oral dosing study are combined in a mathematical model with in vitro measurements of dermal absorption of fluazifop-butyl. Model predictions of the rate and extent of dermal absorption of fluazifop-butyl are compared with the results of dermal absorption studies in human volunteers. Good agreement is found between the model predictions and the experimental measurements. These results have implications for improved risk assessment. The model provides a tool for risk assessment based on both internal dose (e.g. peak plasma concentration, plasma area under the curve) as well as total absorbed dose. However, further work is required to evaluate whether the same techniques are applicable to a wider range of compounds.

scholarly journals Synergistic Effects of Clopidogrel and Fufang Danshen Dripping Pills by Modulation of the Metabolism Target and Pharmacokinetics

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Shitang Ma ◽  
Wenzheng Ju ◽  
Guoliang Dai ◽  
Wenzhu Zhao ◽  
Xiaogui Cheng ◽  
...  
Keyword(s):  
Molecular Simulation ◽  
Time Course ◽  
Peak Plasma ◽  
Synergistic Effects ◽  
Peak Plasma Concentration ◽  
Area Under The Curve ◽  
Compartment Model ◽  
Simulation Method ◽  
Pharmacokinetic Parameters ◽  
Concentration Time

Background and Objective.The aim was to evaluate the synergistic effects of clopidogrel and FDDP by modulating the metabolism target and the pharmacokinetics.Methods. The inhibition effect of FDDP on the CES1 was first investigated by the molecular simulation method, and the synergistic effects on the pharmacokinetics of CPGS were studied as follows: SD rats were treated with oral clopidogrel alone at a dosage of 30 mg/kg or the combination of clopidogrel and FDDP at dosages of 30 mg/kg and 324 mg/kg, respectively, for 21 days. The concentrations of CPGS in the blood plasma samples were determined and the calculated concentrations were used to determine the pharmacokinetic parameters.Results. 20 compounds in FDDP potentially interacted with CES1 target. The CPGS showed a two-compartment model pharmacokinetic profile. The concentration-time course of CPGS was not changed by FDDP, but FDDP decreased the peak plasma concentration and area under the curve of CPGS.Conclusion. The CES1’s activity could be partly inhibited by FDDP through the molecular simulation investigation. The concentration-time course of CPGS was altered slightly by FDDP. The results demonstrated the synergistic effects of clopidogrel and FDDP by modulating both the pharmacokinetics and the target metabolism.

scholarly journals Expression of angiogenic markers in jawbones and femur in a rat model treated with zoledronic acid

2022 ◽  
Vol 15 (1) ◽  
Author(s):  
Jing Wen Li ◽  
Jing Yi Wang ◽  
Ru Qing Yu ◽  
Lei Huo ◽  
Li Wu Zheng
Keyword(s):  
Gene Expression ◽  
Zoledronic Acid ◽  
Soft Tissue ◽  
Rat Model ◽  
Pcr Analysis ◽  
Control Group ◽  
Tissue Healing ◽  
Significant Difference ◽  
And Control ◽  
Group 1

Abstract Objectives This study aimed to investigate the gene expression of angiogenic marker in surgically treated jawbones and femur on a rat model administrated with zoledronic acid. Results No soft tissue fenestration or bone exposure was found in femur. Delayed soft tissue healing was found in both ZA group (3 in mandible, 4 in maxilla) and control group (1 in mandible, 2 in maxilla), while exposed bone was found only in the ZA group (1 in maxilla, 2 in mandible). RT-PCR analysis demonstrated no significant difference in gene expression of angiogenetic markers between ZA-treated and control groups in femur and mandible. In the maxilla, the expression of VEGFA and VEGFR-2 in medium-term ZA group was significantly down-regulated compared with that in the control. The ZA treatment does not change significantly the expression of the angiogenic factors in femur and mandible, but significantly downregulates the expression in maxilla in this rat model. The angiogenesis inhibition may contribute to the development of MRONJ but does not play a key role.

scholarly journals PHARMACOKINETIC DRUG INTERACTION BETWEEN CLOPIDOGREL AND ESOMEPRAZOLE IN ADULT HEALTHY MALE VOLUNTEERS

2017 ◽  
Vol 10 (7) ◽  
pp. 336
Author(s):  
Bhargav K ◽  
Venkata Subbareddy B ◽  
Venkata Sivakrishna K ◽  
Himaja G ◽  
Samuel Gideon Georgep ◽  
...  
Keyword(s):  
Peak Plasma ◽  
Peak Plasma Concentration ◽  
Antiplatelet Agent ◽  
Pharmacokinetic Profile ◽  
Apparent Volume ◽  
Pharmacokinetic Parameters ◽  
Poor Responders ◽  
Healthy Male ◽  
Indwelling Catheter ◽  
Significant Difference

Objective: Proton pump inhibitors (PPIs) are known to impair cytochrome P2C19 mediated activation of clopidogrel, the antiplatelet agent used for cardiovascular risk prevention. Esomeprazole is an optical isomer of omeprazole with better efficacy and tolerability than conventional PPIs. Esomeprazole is often co-administered with clopidogrel considering the risk of associated gastrointestinal bleeding. This study was designed to determine the effect of esomeprazole on the mean pharmacokinetic profile clopidogrel.Methods: A total of 14 adult healthy male participants who volunteered participation were enrolled, randomized equally into two cross-over sequences, dosed with clopidogrel and clopidogrel + esomeprazole in respective periods. Blood samples were collected through antecubital or forearm vein indwelling catheter. Concentration of clopidogrel parent prodrug in isolated plasma was determined using validated sensitive liquid chromatography – mass spectrometry. Pharmacokinetic modeling was carried out using PKSOLVER add-in for Microsoft Excel.Results: The pharmacokinetic profile of clopidogrel was non-significantly altered by esomeprazole. Statistically significant difference in peak plasma concentration, apparent volume of distribution, and clearance of clopidogrel was observed only during period II in participants co-dosed with esomeprazole (p=0.0483, 0.0011, and 0.0015, respectively). All other primary and secondary pharmacokinetic parameters displayed minor alterations during either period (p>0.05).Conclusion: The non-significant alteration of clopidogrel pharmacokinetics by esomeprazole can be potentiated by underlying predisposing factors such as the presence of CYP2C19 allelic variants and increasing the risk of cardiovascular events. Hence, co-administration of clopidogrel and esomeprazole should be under clinical monitoring and is not recommended in poor responders of antiplatelet therapy with clopidogrel.

scholarly journals The Effects of Acute Hydrogen Sulfide Poisoning on Cytochrome P450 Isoforms Activity in Rats

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Xianqin Wang ◽  
Mengchun Chen ◽  
Xinxin Chen ◽  
Jianshe Ma ◽  
Congcong Wen ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Hydrogen Sulfide ◽  
Rat Plasma ◽  
Pharmacokinetic Parameters ◽  
Control Group ◽  
Upper Respiratory Tract ◽  
Significant Difference ◽  
Cytochrome P450 Isoforms ◽  
Upper Respiratory ◽  
And Control

Hydrogen sulfide (H2S) is the second leading cause of toxin related death (after carbon monoxide) in the workplace. H2S is absorbed by the upper respiratory tract mucosa, and it causes histotoxic hypoxemia and respiratory depression. Cocktail method was used to evaluate the influences of acute H2S poisoning on the activities of cytochrome P450 isoforms CYP2B6, CYP2D6, CYP3A4, CYP1A2, CYP2C19, and CYP2C9, which were reflected by the changes of pharmacokinetic parameters of six specific probe drugs, bupropion, metoprolol, midazolam, phenacetin, omeprazole, and tolbutamide, respectively. The experimental rats were randomly divided into two groups, control group and acute H2S poisoning group (inhaling 300 ppm for 2 h). The mixture of six probes was given to rats by oral administration and the blood samples were obtained at a series of time points through the caudal vein. The concentrations of probe drugs in rat plasma were measured by LC-MS. The results for acute H2S poisoning and control groups were as follows: there was a statistically significant difference in the AUC andCmaxfor bupropion, metoprolol, phenacetin, and tolbutamide, while there was no statistical pharmacokinetic difference for midazolam and omeprazole. Acute H2S poisoning could inhibit the activity of CYP2B6, CYP2D6, CYP1A2, and CYP2C9 in rats.

scholarly journals Comparative Evaluation of the Effects of Atorvastatin and Lovastatin on the Pharmacokinetics of Aliskiren in Rats

2021 ◽  
Vol 50 (3) ◽  
pp. 829-837
Author(s):  
AMAL SHARAF ◽  
KAMAL A. EL-SHAZLY ◽  
AMERA ABD EL LATIF ◽  
KHALED S. ABDELKAWY ◽  
FAWZY ELBARBRY ◽  
...  
Keyword(s):  
Peak Plasma ◽  
Heart Diseases ◽  
Peak Plasma Concentration ◽  
Area Under The Curve ◽  
Control Treatment ◽  
Pharmacokinetic Parameters ◽  
Albino Rats ◽  
Liquid Chromatography Tandem Mass ◽  
Group 2 ◽  
Underlying Mechanisms

The worldwide increase in the number patients with high blood pressure poses serious clinical challenges. Little is known regarding the interactions between the various drugs used to treat heart diseases. The present study evaluates and compares the effects of administration of multiple doses of atorvastatin or lovastatin on the pharmacokinetics of aliskiren in rats in an effort to determine their underlying mechanisms. A total of 90 healthy female albino rats were randomly divided into three groups. All groups were treated with aliskiren by oral gavage at 8.57 mg/kg daily for 14 days. In addition to aliskiren, group 2 received atorvastatin at a dose of 1.143 mg/kg for 7 days. In addition to aliskiren, group 3 received lovastatin at a dose of 1.143 mg/kg for 7 days. After blood samples were collected at specific time intervals, aliskiren concentrations were determined using liquid chromatography-tandem mass spectrometry. Relative to the control treatment, atorvastatin treatment resulted in non-significant alterations in the pharmacokinetic parameters of aliskiren. In contrast, lovastatin resulted in a significant increase in the area under the curve, peak plasma concentration, and elimination half-life by 21, 10, and 72%, respectively. Additionally, lovastatin significantly reduced oral clearance by 23%. Inhibition of aliskiren metabolism via the hepatic CYP3A subfamily and/or inhibition of intestinal P-glycoprotein and/or the CYP3A subfamily was identified as a possible mechanism. This study is the first to report that only lovastatin causes a marked increase in aliskiren bioavailability. Caution should be taken when lovastatin and aliskiren are administrated concomitantly in clinical practice.

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