scholarly journals Coexisting flavonoids and administration route effect on pharmacokinetics of Puerarin in MCAO rats

2020 ◽  
Vol 15 (1) ◽  
pp. 449-457
Author(s):  
Pengyue Li ◽  
Linying Zhong ◽  
Linjie Yang ◽  
Jie Bai ◽  
Yang Lu ◽  
...  
Keyword(s):  
Intravenous Administration ◽  
High Performance ◽  
Area Under The Curve ◽  
Artery Occlusion ◽  
Pharmacokinetic Parameters ◽  
Time Data ◽  
Comparative Pharmacokinetic ◽  
Radix Puerariae ◽  
Cerebral Artery Occlusion ◽  
Pharmacokinetic Behavior

AbstractA pharmacokinetic comparison was made to evaluate the influence from other components in the Radix Puerariae Extract on pharmacokinetic behavior of Puerarin. Samples of blood and brain were collected by microdialysis and determined by high-performance liquid chromatography–mass spectrometry (MS)/MS. Pharmacokinetic parameters were estimated from the concentration versus time data using non-compartmental methods. In addition, a comparative pharmacokinetic study of Puerarin in stroke rats was studied after administration of the Radix Puerariae Extract via different routes to find an effective way to deliver drug into brain. Obvious pharmacokinetic differences were also observed in comparison between the Puerarin group and the Radix Puerariae Extract group based on middle cerebral artery occlusion (MCAO) rats. The Cmax and area under the curve (AUC) of Puerarin in olfactory bulb of the Extract group significantly reduced when it was intravenously administered. However, the AUCs of Puerarin in plasma are 134.72 and 1707.02 mg/L min, via intranasal and intravenous administration of the Radix Puerariae Extract, respectively. The AUC of the intranasal group in brain is seven times higher than that of intravenous administration. Other ingredients in the Extract may affect the disposition of Puerarin and its transportation through the blood–brain barrier via intravenous administration. But intranasal administration is an effective route to deliver isoflavone-C-glycoside with poor hydrophilicity into brain.

Comparative Pharmacokinetic of Three Sulfadiazine Suspensions by Oral Administration in Chickens

2016 ◽  
Vol 8 (2) ◽  
pp. 122
Author(s):  
Zhi-Qiang Wang ◽  
Han-Song Li ◽  
Xia Xiao ◽  
Jian-Bing Wang
Keyword(s):  
Plasma Concentration ◽  
Broiler Chickens ◽  
High Performance ◽  
Area Under The Curve ◽  
Pharmacokinetic Analysis ◽  
Pharmacokinetic Parameters ◽  
Peak Time ◽  
Comparative Pharmacokinetic ◽  
Elimination Half ◽  
Maximal Plasma

<p>The chemotherapeutics, sulfadiazine (SDA) and trimethoprim (TMP), are extensively used in a variety of animal species. In this study, a pharmacokinetic analysis was performed to compare the bioequivalence of a combined SDA and TMP product against existing licensed SDA and TMP formulations in broiler chickens. Three groups of 15 birds were administered a single dose of either the test formulation or a reference oral suspension. The plasma concentration of SDA and TMP were determined by reverse-phase high performance liquid chromatography (HPLC), and the maximal plasma concentration (C<sub>max</sub>), area under the curve (AUC), the peak time (T<sub>max</sub>), mean residence time (MRT) and elimination half-life (T<sub>1/2</sub>), were calculated for SDA. The combined formulation I and II reference suspension exhibited almost identical concentration-time curves, and ANOVA analyses of the pharmacokinetic parameters identified no significant differences between the reference preparations and the test one. Furthermore the AUC and C<sub>max</sub> values of the SDA active ingredient were not significantly different. The I formulation was bioequivalent with both II and III (80-125% and 70–143%, respectively, at the 90% confidence interval). In conclusion, the combined SDA and TMP product was bioequivalent with both existing commercially available SDA suspensions and can be used interchangeably in veterinary medical practice.</p>

Phase I clinical and pharmacokinetic study of oral etoposide phosphate.

1995 ◽  
Vol 13 (1) ◽  
pp. 200-209 ◽  
Author(s):  
C Sessa ◽  
M Zucchetti ◽  
T Cerny ◽  
O Pagani ◽  
F Cavalli ◽  
...  
Keyword(s):  
Phase I ◽  
Intravenous Administration ◽  
High Performance ◽  
Plasma Concentrations ◽  
Area Under The Curve ◽  
Pharmacokinetic Parameters ◽  
Pharmacokinetic Studies ◽  
Oral Etoposide ◽  
Validation Data ◽  
Etoposide Phosphate

PURPOSE To determine the bioavailability (F) and the pharmacokinetic profile of both etoposide and its prodrug, etoposide phosphate, after oral and intravenous administration of etoposide phosphate, and to determine the maximum-tolerable dose (MTD) of oral etoposide phosphate administered daily for 5 consecutive days every 3 weeks. In addition, we sought to develop and validate two limited-sampling models (LSMs) to predict the etoposide area under the curve (AUC) 24 hours after administration of oral and intravenous etoposide phosphate. PATIENTS AND METHODS In the F part of the study, patients were assessed for pharmacokinetic studies after one oral and one intravenous administration of the same dose of etoposide phosphate. Etoposide phosphate and etoposide plasma concentrations were assayed by high-performance liquid chromatography (HPLC). To develop LSMs after oral and intravenous administration, patients were randomized between the training and validation data sets. In the phase I part of the study, which followed the F part, the dose of etoposide phosphate was escalated from 50 mg/m2/d for etoposide equivalents for 5 days to 220 mg/m2/d for 5 days. RESULTS Forty adult patients with solid tumors or lymphoma entered the study and 35 were assessable for toxicity. The MTDs were defined as 175 mg/m2 and 220 mg/m2 in previously treated and untreated patients, respectively. Neutropenia was dose-limiting, with high interpatient variability. Within 15 minutes after intravenous administration, etoposide phosphate was no longer detectable in plasma, and it was never detectable after oral administration. Plasma concentrations and pharmacokinetic parameters of etoposide following etoposide phosphate were comparable to those reported for etoposide. The relative F (mean +/- SD) of etoposide after oral etoposide phosphate was 76 +/- 27%, with a range of 37% to 144%. CONCLUSION The clinical and pharmacokinetic results of this study confirm the prodrug hypothesis of etoposide phosphate. Although firm conclusions cannot be drawn, the F of oral etoposide phosphate seems to be comparable to or only slightly better than that of oral etoposide.

Study on Integrated Pharmacokinetics of Gardenia Acid and Geniposide: Time-Antioxidant Efficacy after Oral Administration of Huanglian–Zhizi Couplet Medicine from Huang–Lian–Jie–Du–Tang in MCAO Rats

2014 ◽  
Vol 42 (02) ◽  
pp. 393-407 ◽  
Author(s):  
Linmei Pan ◽  
Jing Zhou ◽  
Huaxu Zhu ◽  
Wenzhe Wang ◽  
Meng Zhang ◽  
...  
Keyword(s):  
Oral Administration ◽  
High Performance ◽  
Artery Occlusion ◽  
Pharmacokinetic Parameters ◽  
Sprague Dawley ◽  
Concentration Time ◽  
Analysis System ◽  
Data Analysis System ◽  
Index Components ◽  
Cerebral Artery Occlusion

Huanglian–Zhizi couplet medicine comes from classical prescription Huang–Lian–Jie–Du–Tang (HLJDT), which has been proven by previous researches to be an effective compound for cerebral ischemia. This paper explores the integrated pharmacokinetics of gardenia acid and geniposide-time-antioxidant efficacy after the oral administration of Huanglian–Zhizi couplet medicine from HLJDT in rats with middle cerebral artery occlusion (MCAO). To investigate the differences in pharmacokinetics and antioxidant effect of Huanglian–Zhizi and HLJDT in MCAO rats, which have been scarcely reported, an oral dose, 24 crud drug g/kg, of Huanglian–Zhizi and 40 crud drug/kg of HLJDT were administered in two groups of normal rats and two groups of Sprague–Dawley (SD) MCAO rats, respectively. At different time points, concentrations of gardenia acid and geniposide were determined by high performance liquid chromatography (HPLC), and levels of superoxide dismutase (SOD) were calculated by ELIASA. Pharmacokinetic parameters including AUC, MRT, t1/2, T max , C max were estimated by statistical moment analysis using a data analysis system (DAS) 2.0. An AUC based on weighting approach was used for integrating gardenia acid and geniposide. Finally, the concentration-time efficacy profiles were obtained. The integrated pharmacokinetics profiles of index components could reveal the pharmacokinetics behavior of Huanglian–Zhizi and HLJDT, corresponding to the antioxidant efficacy.

scholarly journals Compartmental Pharmacokinetics of the Antifungal Echinocandin Caspofungin (MK-0991) in Rabbits

2001 ◽  
Vol 45 (2) ◽  
pp. 596-600 ◽  
Author(s):  
Andreas H. Groll ◽  
Bryan M. Gullick ◽  
Ruta Petraitiene ◽  
Vidmantas Petraitis ◽  
Myrna Candelario ◽  
...  
Keyword(s):  
High Performance ◽  
Pharmacokinetic Model ◽  
Area Under The Curve ◽  
Apparent Volume ◽  
Volume Of Distribution ◽  
Pharmacokinetic Parameters ◽  
Chromatography Method ◽  
Opportunistic Fungi ◽  
The Mean ◽  
Liquid Chromatography Method

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.

scholarly journals Predicting experimental success: a retrospective case-control study using the rat intraluminal thread model of stroke

2020 ◽  
Vol 13 (12) ◽  
pp. dmm044651
Author(s):  
Lisa Liebenstund ◽  
Mark Coburn ◽  
Christina Fitzner ◽  
Antje Willuweit ◽  
Karl-Josef Langen ◽  
...  
Keyword(s):  
Operating Characteristic ◽  
Characteristic Curve ◽  
Disease Model ◽  
Area Under The Curve ◽  
Artery Occlusion ◽  
Retrospective Case ◽  
Stroke Research ◽  
Left And Right ◽  
Cerebral Artery Occlusion ◽  
Control Study

ABSTRACTThe poor translational success rate of preclinical stroke research may partly be due to inaccurate modelling of the disease. We provide data on transient middle cerebral artery occlusion (tMCAO) experiments, including detailed intraoperative monitoring to elaborate predictors indicating experimental success (ischemia without occurrence of confounding pathologies). The tMCAO monitoring data (bilateral cerebral blood flow, CBF; heart rate, HR; and mean arterial pressure, MAP) of 16 animals with an ‘ideal’ outcome (MCA-ischemia), and 48 animals with additional or other pathologies (subdural haematoma or subarachnoid haemorrhage), were checked for their prognostic performance (receiver operating characteristic curve and area under the curve, AUC). Animals showing a decrease in the contralateral CBF at the time of MCA occlusion suffered from unintended pathologies. Implementation of baseline MAP, in addition to baseline HR (AUC, 0.83, 95% c.i. 0.68 to 0.97), increased prognostic relevance (AUC, 0.89, 95% c.i. 0.79 to 0.98). Prediction performance improved when two additional predictors referring to differences in left and right CBF were considered (AUC, 1.00, 95% c.i. 1.0 to 1.0). Our data underline the importance of peri-interventional monitoring to verify a successful experimental performance in order to ensure a disease model as homogeneous as possible.

Exposure to chloroquine in male adults and children aged 9–11 years with malaria due to Plasmodium vivax

2020 ◽  
Author(s):  
Michelle Valeria Dias Ferreira Vieira ◽  
José Luiz Fernandes Vieira
Keyword(s):  
Plasmodium Vivax ◽  
High Performance ◽  
Plasma Concentrations ◽  
Area Under The Curve ◽  
Time Profile ◽  
Pharmacokinetic Parameters ◽  
Older Children ◽  
Asexual Blood Stage ◽  
Adults And Children ◽  
A Prospective Study

Abstract Background Chloroquine is effective against the asexual blood stage of Plasmodium vivax. A high proportion of children are underdosed with the drug, but there are no studies comparing chloroquine exposure in adults and children aged 8–11 years old. The present study intends to compare these populations using the area under the curve (AUC) derived from the plasma concentration-time profile in patients with P. vivax. Methods A prospective study of cases was performed on male children (aged 9–11 years) and adults with vivax malaria. Blood samples were collected after several days of treatment. Chloroquine was measured by high-performance liquid chromatography. A non-compartmental pharmacokinetic model was used to calculate the pharmacokinetic parameters of the drug. Results A total of 20 children and 25 adults were included in the study. Plasma concentrations of chloroquine in older children ranged from 67 to 1112 ng/ml, and in adults the value ranged from 74 to 1147 ng/ml. The AUC to the last measurable concentration and to infinite was significantly lower in children than in adults, indicating a lower exposure to the drug. Conclusion These data demonstrate lower exposure to chloroquine in children, which corroborates the importance of optimising the doses of chloroquine in the study age band to ensure adequate exposure to the drug.

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
Keyword(s):  
Body Weight ◽  
Oral Dose ◽  
High Performance ◽  
Area Under The Curve ◽  
Total Body Weight ◽  
Apparent Volume ◽  
Pharmacokinetic Parameters ◽  
Maximum Plasma ◽  
Significant Difference ◽  
Total Body

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.

Lack of Pharmacokinetic Interaction Between the Antimigraine Compound, Almotriptan, and Propranolol in Healthy Volunteers

Cephalalgia ◽  
2001 ◽  
Vol 21 (1) ◽  
pp. 61-65 ◽  
Author(s):  
JC Fleishaker ◽  
TA Sisson ◽  
BJ Carel ◽  
NE Azie
Keyword(s):  
High Performance ◽  
Treatment Effects ◽  
Vital Signs ◽  
Area Under The Curve ◽  
Pharmacokinetic Interaction ◽  
Concomitant Administration ◽  
Crossover Design ◽  
Pharmacokinetic Parameters ◽  
Percent Confidence Interval ◽  
Healthy Male

This study was designed to assess the pharmacokinetics of almotriptan, a 5-HT1B/1D agonist, when administered in the presence and absence of propranolol. Healthy male ( n = 10) and female ( n = 2) volunteers received (i) 80 mg propranolol twice daily for 7 days and 12.5 mg almotriptan on day 7, and (ii) 12.5 mg almotriptan on day 7, according to a two-way crossover design. Plasma and urinary almotriptan concentrations were measured by high performance liquid chromatography (HPLC) methods. Treatment effects on pharmacokinetic parameters were assessed by analysis of variance (anova). Statistically significant differences between treatments in area under the curve (AUC), clearance, and half-life were observed ( P < 0.03), but these differences were < 7%. Ninety percent confidence interval analysis of log-transformed pharmacokinetic parameters showed that the treatments were equivalent. Adverse events were mild to moderate in intensity, and no treatment effects on vital signs were observed. The results show that propranolol has no effect on the pharmacokinetics of almotriptan. Concomitant administration of the two drugs is well tolerated.

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