scholarly journals Neuroprotective Effects of Red Ginseng Saponins in Scopolamine-Treated Rats and Activity Screening Based on Pharmacokinetics

Molecules ◽  
2019 ◽  
Vol 24 (11) ◽  
pp. 2136
Author(s):  
Jianbo Chen ◽  
Meijia Li ◽  
Di Qu ◽  
Yinshi Sun
Keyword(s):  
Superoxide Dismutase ◽  
Plasma Concentration ◽  
Protective Effect ◽  
Peak Plasma ◽  
Peak Plasma Concentration ◽  
Area Under The Curve ◽  
Normal Group ◽  
Cerebral Injury ◽  
Red Ginseng ◽  
Model Group

Ginseng has been used to alleviate age-related dementia and memory deterioration for thousands of years. This study investigated the protective effect of red ginseng saponins against scopolamine-induced cerebral injury. Meanwhile, pharmacokinetics of ginsenosides in normal and scopolamine-treated rats were compared. After scopolamine injection, glutathione, catalase and superoxide dismutase levels were significantly decreased when compared with control group. Compared with SA group, pretreatment of rats with red ginseng saponins could increase glutathione, catalase and superoxide dismutase level. Treatment with red ginseng saponins significantly decreased malondialdehyde level. In the pharmacokinetic analysis, a pattern recognition analysis method was used to investigate the pharmacokinetics of the absorbed compounds in blood. The pharmacokinetic parameters of Rg1, Rg2, Rh3, Rg5 and Rk1 in model group had higher area under the curve (AUC), mean residence time (MRT) and peak plasma concentration (Cmax) values; area under the curve (AUC) values and peak plasma concentration (Cmax) of model group was significantly different from that of normal group (p < 0.05). The Cmax value of Rk3, Rh1, Rh2 and Rh4 in model group was higher than normal group, but their AUC values were not significantly different. There was no significantly difference in time at Cmax (Tmax), AUC and Cmax values of Rb1, Rb2 Re, Rc, Rd and Rf between the model and normal group. 16 ginsenosides were grouped into three separate clusters according to principal component analysis (PCA) score plot based on pharmacokinetic data. The results suggested red ginseng saponins have significant protective effect against scopolamine-induced memory deficit and scopolamine-induced rats could lead to the changes of pharmacokinetic behaviors of ginsenosides.

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 Evaluation of the impact of renal impairment on the pharmacokinetics of glasdegib in otherwise healthy volunteers

2021 ◽  
Author(s):  
Naveed Shaik ◽  
Robert R. LaBadie ◽  
Brian Hee ◽  
Geoffrey Chan
Keyword(s):  
Plasma Concentration ◽  
Renal Impairment ◽  
Peak Plasma ◽  
Severe Renal Impairment ◽  
Peak Plasma Concentration ◽  
Safety Data ◽  
Normal Group ◽  
Open Label ◽  
Post Dose ◽  
The Impact

Abstract Purpose Glasdegib is being developed for indications in myeloid malignancies. The effect of renal impairment on the pharmacokinetics (PK) of a single, oral, 100-mg glasdegib dose under fasted conditions was assessed. Methods Open-label, parallel-group study (NCT03596567). Participants of good general health were selected and categorized, based on their estimated glomerular filtration rate, into normal (≥ 90 mL/min), moderate (≥ 30 to < 60 mL/min), or severe (< 30 mL/min) renal impairment groups. Blood samples were collected up to 120 h post-dose. PK exposure parameters were calculated using non-compartmental analysis. Results All 18 participants completed the study. Respectively, ratios of adjusted geometric means (90% confidence interval) for glasdegib area under the curve from time 0 to infinity and peak plasma concentration versus normal participants were 205% (142–295%) and 137% (97–193%) in the moderate group, and 202% (146–281%) and 120% (77–188%) in the severe group. Glasdegib median time to peak plasma concentration was 2.0 h in both impairment groups and 1.5 h in the normal group. Mean oral clearance was decreased by approximately 50% in both renal impairment groups compared with the normal group. The plasma-free fraction of glasdegib was not altered by renal impairment. Five all-causality adverse events were reported in three participants; two were considered treatment-related. Conclusion The similar changes in exposure observed for participants with renal impairment, coupled with the known safety data from clinical experience, suggest that a lower starting dose of glasdegib may not be required for moderate or severe renal impairment. Trial registration: ClinicalTrials.gov: NCT03596567 (started May 17, 2018).

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.

Psychopharmacology of Attention Deficit Disorder: Pharmacokinetic, Neuroendocrine, and Behavioral Measures Following Acute and Chronic Treatment with Methylphenidate

PEDIATRICS ◽  
1982 ◽  
Vol 69 (6) ◽  
pp. 688-694
Author(s):  
Sally E. Shaywitz ◽  
Robert D. Hunt ◽  
Peter Jatlow ◽  
Donald J. Cohen ◽  
J. Gerald Young ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Attention Deficit ◽  
Attention Deficit Disorder ◽  
Rating Scale ◽  
Peak Plasma ◽  
Peak Plasma Concentration ◽  
Area Under The Curve ◽  
Lag Phase ◽  
The Mean ◽  
Mean Concentration

Despite the frequent use of methylphenidate (MPH) in school-aged children with disorders of attention, impulsivity, and activity regulation (attention deficit disorder, ADD), little is known of its clinical pharmacology. The pharmacokinetics of MPH as well as its effects on growth hormone and prolactin were examined after oral administration in 14 boys with ADD ranging in age from 7 to 12 years (mean 10.4 years). Peak concentrations determined in these acute studies were compared with concentrations obtained two hours after MPH administration in another group of children with ADD who were receiving MPH chronically. After a lag phase of approximately ½ to 1 hour, MPH reached a peak plasma concentration at 2.5 ± 0.65 hours after 0.34 mg/kg and 1.9 ± 0.82 hours after 0.65 mg/kg (mean ± SD). Terminal half-lives were 2.53 ± 0.59 and 2.61 ± 0.29 hours after administration of 0.34 and 0.65 mg/kg, respectively. Observed maximal concentrations ranged from 11.2 ± 2.7 ng/ml after administration of 0.34, and 20.2 ± 9.1 ng/ml after administration of 0.65 mg/kg. The mean area under the curve after administration of 0.65 mg/kg was approximately double that calculated at 0.34 mg/kg. Plasma growth hormone increased significantly from an initial (pre-MPH) mean concentration of 4.4 to peak at two hours at 10.5 ng/ml. Prolactin concentration declined significantly from a pre-MPH level of 9.5 to a nadir at 1½ hours of 3.80 ng/ml, supporting the notion that MPH is acting via central dopaminergic mechanisms. MPH concentrations in children receiving doses of 0.34 mg/kg chronically averaged 8.00 ± 0.91 at two hours, after medication, approximating the mean concentration at the same time observed in the acute study. The concentration of MPH in single "spot" samples obtained at two to three hours after administration of medication were significantly correlated with the percentage of improvement in the abbreviated Conners rating scale, indicating a relationship between plasma MPH concentration and clinical response.

Pharmacokinetics of Rapacuronium in Infants and Children with Intravenous and Intramuscular Administration

2000 ◽  
Vol 92 (2) ◽  
pp. 376-376 ◽  
Author(s):  
Lynne M. Reynolds ◽  
Andrew Infosino ◽  
Ronald Brown ◽  
Jim Hsu ◽  
Dennis M. Fisher
Keyword(s):  
Plasma Concentration ◽  
Peak Plasma ◽  
Peak Plasma Concentration ◽  
Pediatric Anesthesia ◽  
Infants And Children ◽  
Intramuscular Administration ◽  
Pharmacokinetic Analysis ◽  
Intravenous Route ◽  
Population Pharmacokinetic ◽  
In Infants And Children

Background A nondepolarizing muscle relaxant with an onset and offset profile similar to succinylcholine is desirable for pediatric anesthesia. The onset and offset of rapacuronium are rapid in children. In the current study, the authors determined its pharmacokinetic characteristics in children. In addition to administering rapacuronium by the usual intravenous route, the authors also gave rapacuronium intramuscularly to determine uptake characteristics and bioavailability. Methods Forty unpremedicated patients aged 2 months to 3 yr were anesthetized with halothane, 0.82-1.0% end-tidal concentration. When anesthetic conditions were stable, rapacuronium was injected either into a peripheral vein (2 mg/kg for infants, 3 mg/kg for children) or a deltoid muscle (2.8 mg/kg for infants, 4.8 mg/kg for children). Four venous plasma samples were obtained from each subject 2-240 min after rapacuronium administration. A mixed-effects population pharmacokinetic analysis was applied to these values to determine bioavailability, absorption rate constant, and time to peak plasma concentration with intramuscular administration. Results Plasma clearance was 4.77 ml x kg(-1) x min(-1) + 8.48 ml/min. Intramuscular bioavailability averaged 56%. Absorption from the intramuscular depot had two rate constants: 0.0491 min(-1) (72.4% of absorbed drug) and 0.0110 min(-1) (27.6% of the absorbed drug). Simulation indicated that plasma concentration peaks 4.0 and 5.0 min after intramuscular rapacuronium in infants and children, respectively, and that, at 30 min, less than 25% of the administered dose remains to be absorbed from the intramuscular depot. Conclusions In infants and children, rapacuronium's clearance and steady state distribution volume are less than in adults. After intramuscular administration, bioavailability is 56%, and plasma rapacuronium concentrations peak within 4 or 5 min.

scholarly journals Effect of food on the pharmacokinetics and therapeutic efficacy of 4-phenylbutyrate in progressive familial intrahepatic cholestasis

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Satoshi Nakano ◽  
Shuhei Osaka ◽  
Yusuke Sabu ◽  
Kei Minowa ◽  
Saeko Hirai ◽  
...  
Keyword(s):  
Plasma Concentration ◽  
Intrahepatic Cholestasis ◽  
Clinical Symptoms ◽  
Peak Plasma ◽  
Oral Treatment ◽  
Peak Plasma Concentration ◽  
Open Label ◽  
Time Curve ◽  
Single Dose Study ◽  
Progressive Familial Intrahepatic Cholestasis

AbstractProgressive familial intrahepatic cholestasis (PFIC), a rare inherited disorder, progresses to liver failure in childhood. We have shown that sodium 4-phenylbutyrate (NaPB), a drug approved for urea cycle disorders (UCDs), has beneficial effects in PFIC. However, there is little evidence to determine an optimal regimen for NaPB therapy. Herein, a multicenter, open-label, single-dose study was performed to investigate the influence of meal timing on the pharmacokinetics of NaPB. NaPB (150 mg/kg) was administered orally 30 min before, just before, and just after breakfast following overnight fasting. Seven pediatric PFIC patients were enrolled and six completed the study. Compared with postprandial administration, an approved regimen for UCDs, preprandial administration significantly increased the peak plasma concentration and area under the plasma concentration-time curve of 4-phenylbutyrate by 2.5-fold (95% confidential interval (CI), 2.0–3.0;P = 0.003) and 2.4-fold (95% CI, 1.7–3.2;P = 0.005). The observational study over 3 years in two PFIC patients showed that preprandial, but not prandial or postprandial, oral treatment with 500 mg/kg/day NaPB improved liver function tests and clinical symptoms and suppressed the fibrosis progression. No adverse events were observed. Preprandial oral administration of NaPB was needed to maximize its potency in PFIC patients.

Safety, Tolerability, and Pharmacokinetics of Sumatriptan in Healthy Subjects Following Ascending Single Intranasal Doses and Multiple Intranasal Doses

Cephalalgia ◽  
1997 ◽  
Vol 17 (4) ◽  
pp. 541-550 ◽  
Author(s):  
KHP Moore ◽  
EK Hussey ◽  
S Shaw ◽  
E Fuseau ◽  
C Duquesnoy ◽  
...  
Keyword(s):  
Plasma Concentration ◽  
Adverse Events ◽  
Peak Plasma ◽  
Peak Plasma Concentration ◽  
Dose Range ◽  
Maximum Plasma ◽  
Multiple Doses ◽  
To Receive ◽  
Intranasal Spray ◽  
Female Subjects

The delivery of sumatriptan doses intranasally could add greater flexibility in the treatment of migraine than is possible with the currently available subcutaneous and oral sumatriptan preparations. Two independent double-blind, randomized, placebo-controlled clinical studies were conducted to evaluate the safety, tolerability and pharmacokinetics of intranasally administered sumatriptan following ascending single doses (three different dose levels) and multiple doses. In the four-way crossover, ascending-dose study, 20 healthy female subjects were randomized to receive on separate occasions single intranasal spray doses of 5, 10, or 20 mg sumatriptan (as the hemisulphate salt) or placebo into one nostril. Adverse events were mild and consisted mainly of bitter taste at the back of the throat and events typical of sumatriptan administered by other routes (headache, lightheadedness and tingling). Area under the plasma sumatriptan concentration versus time curve (AUC) and peak plasma concentration (Cmax) increased with the dose. Dose proportionality was demonstrated between 5 and 10 mg but not across the dose range 5–20 mg. Time to maximum plasma concentration (tmax) was variable due to multiple peaking. The elimination half-life (t1/2), approximately 2 h, was unaffected by the magnitude of dose. In the two-period, multiple-dose, crossover study, 12 healthy adult male and female subjects were randomized to receive either sumatriptan hemisulphate 20 mg or placebo, administered intranasally as a spray three times a day for 4 days, The two dosing periods were separated by 3 to 14 days. Multiple doses of sumatriptan were well tolerated, with no serious adverse events occurring or withdrawals due to adverse events. All patients reported a mild to moderate drug-related disturbance of taste. Nasal examinations remained normal, and olfactory function was unaffected. The AUC over the first 8 h following dosing (AUC8) and fraction of the dose excreted in the urine (fe; 6.2% vs 3.6%) were similar on Days 1 and 4. Day 4 values were significantly higher (p0.05) for Cmax (16.9 ng/ml vs 13.1 ng/ml), renal clearance (Clr; 19.0 l/h vs 14.2 l/h), and t1/2 (2.18 h vs 1.93 h), and shorter for tmax (0.88 h vs 1.75 h). Some accumulation (22%) occurred over the 4 days of dosing. Serum concentrations of the pharmacologically inactive indole acetic acid metabolite of sumatriptan were fourfold to fivefold higher than corresponding sumatriptan concentrations. Overall, these studies show the sumatriptan intranasal spray formulation is well tolerated, allows rapid absorption of sumatriptan, and results in only a clinically insignificant degree of sumatriptan accumulation upon repeated dosing.

scholarly journals BIOAVAILABILITY AND DISPOSITION KINETICS OF AMOXICILLIN

2015 ◽  
Vol 22 (01) ◽  
pp. 006-012
Author(s):  
Zulfiqar-Ul- Hassan ◽  
Sualeha Riffat ◽  
Aamir Nazir ◽  
Rahat Naseer ◽  
Anila Asghar ◽  
...  
Keyword(s):  
Body Weight ◽  
Plasma Concentration ◽  
Cell Volume ◽  
Packed Cell Volume ◽  
Peak Plasma ◽  
Peak Plasma Concentration ◽  
Assay Method ◽  
Intravenous Route ◽  
Disposition Kinetics ◽  
Kinetics Of

OBJECTIVE: The study was planned to observe the bioavailability anddisposition kinetics of amoxicillin in adult rabbits (irrespective of sex) under healthy anddehydrated conditions. Design: Comparative. Place and duration of study: The study wasconducted at the department of pharmacology, University of Veterinary and Animal Sciences,Lahore from April 2013 to October 2013. Methodology: Initially all rabbits were weighed andtheir packed cell volume (PCV) and other biochemical parameters were observed under normalconditions. Bioavailability and disposition kinetics of amoxicillin (10mg/kg body weight) werestudied in normal rabbits following oral and intravenous route of drug administration. After 10days washout period, these rabbits were made dehydrated by keeping the animals off waterbut not food. The animals with 10% decrease in body weight were declared dehydrated. Theirparameters were again measured. Treated rabbits were administered amoxicillin orally andintravenously (10mg/kg body weight). Samples were drawn at prescribed time. Amoxicillinwas assessed in plasma by using microbiological assay method. Plasma concentration wasanalyzed using non compartmental method. Results: The water deprived or dehydrated rabbitsshowed a significant increase in the packed cell volume, blood glucose and plasma globulins ascompared to the normal rabbits. However, there was a significant (p<0.05 & p<0.01) decreasein body weight, total proteins, albumins and albumin globulin ratio of the dehydrated rabbits.The peak plasma concentration, volume of distribution and rate constant of elimination waslower in the dehydrated rabbits as compared to the normal rabbits. The plasma concentrationof amoxicillin after intravenous administration in dehydrated rabbits had a significant (p<0.05& p<0.01) larger area under curve, area under 1st moment curve, a longer half life and a largermean residence time. Conclusions: The study in the dehydrated rabbits indicated the need ofmodification of dosage regimen.

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