scholarly journals Physostigmine: A Plant Alkaloid Isolated from Physostigma venenosum: A Review on Pharmacokinetics, Pharmacological and Toxicological Activities

2020 ◽  
Vol 10 (1-s) ◽  
pp. 187-190 ◽  
Author(s):  
Gaber El-Saber Batiha ◽  
Luay M. Alkazmi ◽  
Eman H. Nadwa ◽  
Eman K. Rashwan ◽  
Amany Magdy Beshbishy ◽  
...  
Keyword(s):  
Peak Plasma ◽  
Biological Activities ◽  
Peak Plasma Concentration ◽  
Therapeutic Index ◽  
Tricyclic Antidepressant ◽  
Ache Inhibitor ◽  
Short Life Span ◽  
Perennial Shrub ◽  
Butyrylcholinesterase Inhibitor ◽  
Pharmaceutical Molecules

Medicinal plants have been documented as an important source for discovering new pharmaceutical molecules that have been used to treat serious diseases. Strikingly, previous reports stated that natural products and their derived compounds exhibit lesser side effects and improved efficacy than other synthetic counterparts. Physostigmine, a parasympathomimetic plant alkaloid isolated from the West African perennial shrub Physostigma venenosum, it shows a narrow therapeutic index and a short life span, despite its ability to penetrate the blood-brain barrier (BBB). It is a widely known reversible butyrylcholinesterase (BuChE) and acetylcholinesterase (AChE) inhibitor and has been documented to treat various ailments such as Alzheimer’s disease. Pharmacologically, physostigmine was first reported as an antidote for atropine scopolamine and belladonna alkaloids toxicity. Recently, it has been documented as a therapy for treating several ailments including glaucoma, myasthenia gravis and the intoxication caused by tricyclic antidepressant overdoses, anti-histamines, antipsychotics, and benzodiazepines. Physostigmine has been reported to be absorbed from the gastrointestinal tract and showed short half-life, as, after the oral administration of 2 mg of physostigmine salicylate, the peak plasma concentration reached to 30 minutes. This review examines the biological activities, pharmacokinetics, and toxicity of physostigmine extracted from P. venenosum. Keywords: Physostigma venenosum, Physostigmine, pharmacological activities, acetylcholinesterase and butyrylcholinesterase inhibitor.

scholarly journals Herb-Drug Interaction ofPaullinia cupana(Guarana) Seed Extract on the Pharmacokinetics of Amiodarone in Rats

2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Márcio Rodrigues ◽  
Gilberto Alves ◽  
Nulita Lourenço ◽  
Amílcar Falcão
Keyword(s):  
Drug Interaction ◽  
Peak Plasma ◽  
Peak Plasma Concentration ◽  
Systemic Exposure ◽  
Therapeutic Index ◽  
Great Decrease ◽  
Tissue Concentrations ◽  
Paullinia Cupana ◽  
Narrow Therapeutic Index Drug ◽  
First Time

Paullinia cupanais used in weight-loss programs as a constituent of medicinal/dietary supplements. This study aimed to assess a potential herb-drug interaction among a standardized (certified)Paullinia cupanaextract and amiodarone (narrow therapeutic index drug) in rats. In a first pharmacokinetic study rats were simultaneously coadministered with a single dose ofPaullinia cupana(821 mg/kg, p.o.) and amiodarone (50 mg/kg, p.o.), and in a second study rats were pretreated during 14 days withPaullinia cupana(821 mg/kg/day, p.o.) receiving amiodarone (50 mg/kg, p.o.) on the 15th day. Rats of the control groups received the corresponding volume of vehicle. Blood samples were collected at several time points after amiodarone dosing, and several tissues were harvested at the end of the experiments (24 h after dose). Plasma and tissue concentrations of amiodarone and its major metabolite (mono-N-desethylamiodarone) were measured and analysed. A significant reduction in the peak plasma concentration (73.2%) and in the extent of systemic exposure (57.8%) to amiodarone was found in rats simultaneously treated withPaullinia cupanaand amiodarone; a decrease in tissue concentrations was also observed. This paper reports for the first time an herb-drug interaction betweenPaullinia cupanaextract and amiodarone, which determined a great decrease on amiodarone bioavailability in rats.

Pharmacokinetics and Haemostatic Status During Consecutive Infusions of Recom binant Tissue-Type Plasminogen Activator in Patients with Acute Myocardial Infarction

1989 ◽  
Vol 61 (03) ◽  
pp. 497-501 ◽  
Author(s):  
E Seifried ◽  
P Tanswell ◽  
D Ellbrück ◽  
W Haerer ◽  
A Schmidt
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Plasminogen Activator ◽  
Peak Plasma ◽  
Peak Plasma Concentration ◽  
Tissue Type ◽  
Tissue Type Plasminogen Activator ◽  
Precise Control ◽  
Type Plasminogen Activator

SummaryPharmacokinetics and systemic effects of recombinant tissue type plasminogen activator (rt-PA) were determined during coronary thrombolysis in 12 acute myocardial infarction patients using a consecutive intravenous infusion regimen. Ten mg rt-PA were infused in 2 minutes resulting in a peak plasma concentration (mean ±SD) of 3310±950 ng/ml, followed by 50 mg in 1 h and 30 mg in 1.5 h yielding steady state plasma levels of. 2210±470 nglml and 930±200 ng/ml, respectively. All patients received intravenous heparin. Total clearance of rt-PA was 380±74 ml/min, t,½α was 3.6±0.9 min and t,½β was 16±5.4 min.After 90 min, in plasma samples containing anti-rt-PA-IgG to inhibit in vitro effects, fibrinogen was decreased to 54%, plasminogen to 52%, α2-antiplasmin to 25%, α2-macroglobulin to 90% and antithrombin III to 85% of initial values. Coagulation times were prolonged and fibrin D-dimer concentrations increased from 0.40 to 2.7 μg/ml. It is concluded that pharmacokinetics of rt-PA show low interpatient variability and that its short mean residence time in plasma allows precise control of therapy. Apart from its moderate effect on the haemostatic system, rt-PA appears to lyse a fibrin pool in addition to the coronary thrombus.

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.

Preconditioning with ethanol prevents postischemic leukocyte-endothelial cell adhesive interactions

2002 ◽  
Vol 283 (3) ◽  
pp. H1019-H1030 ◽  
Author(s):  
Taiji Yamaguchi ◽  
Catherine Dayton ◽  
T. Shigematsu ◽  
Patsy Carter ◽  
Toshikazu Yoshikawa ◽  
...  
Keyword(s):  
Temporal Pattern ◽  
Receptor Agonist ◽  
Inflammatory Responses ◽  
Peak Plasma ◽  
Peak Plasma Concentration ◽  
Late Phase ◽  
Ethanol Exposure ◽  
Ethanol Ingestion ◽  
Adhesive Interactions ◽  
Ethanol Ethanol

Long-term ethanol consumption at low to moderate levels exerts cardioprotective effects in the setting of ischemia and reperfusion (I/R). The aims of this study were to determine whether 1) a single orally administered dose of ethanol [ethanol preconditioning (EtOH-PC)] would induce a biphasic temporal pattern of protection (early and late phases) against the inflammatory responses to I/R and 2) adenosine and nitric oxide (NO) act as initiators of the late phase of protection. Ethanol was administered as a bolus to C57BL/6 mice at a dose that achieved a peak plasma concentration of ∼45 mg/dl 30 min after gavage and returned to control levels within 60 min of alcohol ingestion. The superior mesenteric artery was occluded for 45 min followed by 60 min of reperfusion beginning 10 min or 1, 2, 3, 4, or 24 h after ethanol ingestion, and the numbers of fluorescently labeled rolling and firmly adherent (stationary) leukocytes in single postcapillary venules of the small intestine were quantified using intravital microscopic approaches. I/R induced marked increases in leukocyte rolling and adhesion, effects that were attenuated by EtOH-PC 2–3 h before I/R (early phase), absent when assessed after 10 min, 1 h, and 4 h of ethanol ingestion, with an even more powerful late phase of protection reemerging when I/R was induced 24 h later. The anti-inflammatory effects of late EtOH-PC were abolished by treatment with adenosine deaminase, an adenosine A2 (but not A1) receptor antagonist, or a NO synthase (NOS) inhibitor during the period of EtOH-PC. Preconditioning with an adenosine A2 (but not an A1) receptor agonist in lieu of ethanol 24 h before I/R mimicked the protective actions of late phase EtOH-PC. Like EtOH-PC, the effect of preconditioning with an adenosine A2 receptor agonist was abrogated by coincident NOS inhibition. These findings suggest that EtOH-PC induces a biphasic temporal pattern of protection against the proinflammatory effects of I/R. In addition, our observations are consistent with the hypothesis that the late phase of EtOH-PC is triggered by NO formed secondary to adenosine A2 receptor-dependent activation of NOS during the period of ethanol exposure.

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.

The Transient Anti-Hypertensive Effect of Phentolamine in Patients Receiving Beta-Blocker Treatment

1973 ◽  
Vol 1 (2) ◽  
pp. 462-464
Author(s):  
Ann Dawson ◽  
Ian Smith ◽  
Brian F Johnson
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Essential Hypertension ◽  
Beta Blocker ◽  
Peak Plasma ◽  
Beta Blockers ◽  
Peak Plasma Concentration ◽  
Hypotensive Effect ◽  
Additional Reduction ◽  
Standing Blood Pressure

In seven hypertensives receiving beta-blocker drugs, an additional reduction in standing blood pressure occurred between 60 and 90 minutes after 40 mg phentolamine by mouth. The occurrence of the postural hypotensive effect was delayed in relation to the reported time of peak plasma concentration of unchanged phentolamine. Supine blood pressure and heart rate were unaffected. Phentolamine has no clinically useful anti-hypertensive effect in conjunction with beta-blockers in patients with essential hypertension.

Bioavailability of Paediatric Mixtures Containing Phenoxymethylpenicillin Calcium or Potassium Salt

1982 ◽  
Vol 10 (5) ◽  
pp. 379-382 ◽  
Author(s):  
Kari Soininen ◽  
Hannu Allonen ◽  
Juhani Posti
Keyword(s):  
Potassium Salt ◽  
Calcium Salt ◽  
Healthy Adult ◽  
Peak Plasma ◽  
Peak Plasma Concentration ◽  
Salt Mixture ◽  
Time To Peak ◽  
Aqueous Mixture ◽  
The Mean ◽  
Adult Volunteers

The bioavailability of the calcium and potassium salts of Phenoxymethylpenicillin (dose 38,000 I.U./kg) was investigated in eight healthy adult volunteers. Administration of the calcium salt as an aqueous oral mixture resulted in a mean peak plasma concentration of 8·52 mg/l (SD 1·96) and that of the potassium salt mixture in a concentration of 8·40 mg/ml (SD 2·61), p > 0·1. The median time-to-peak levels were 0·75 h and 1·0 h, respectively (p > 0·1). The mean AUC for the calcium salt mixture was 16·94 mg·h/l (SD 3·31) and for the potassium salt 15·84 mg·h/l (SD 4·76), p > 0·09. These findings confirm that an aqueous mixture of calcium phenoxymethylpenicillin is equivalent to a mixture of potassium Phenoxymethylpenicillin.

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.

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