Repercussion of piperine on pharmacokinetics parameters of eletriptan in albino rats: Involvement of CYP3A and P-GP inhibition

Eletriptan is at the type of triptan medication suggested for the management of episodes of severe headache with or without aura. Piperine (1-piperoylpiperidine) is a pure alkaloid as well as the basic tanginess material from the pipli and peppercorn. There are signs that piperine inhibits Cytochrome P-450 enzymes and P-glycoprotein, rather than arouses, drug metabolism generally, thus increasing the bioavailability and effect of several medications. The analysis was undertaken to assess the results of Piperine on the pharmacokinetics of Eletriptan. Samples of blood were taken at different time points for example 0 (predose), 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 6.0, 8.0, 12, 24 hours post-treatment. The plasma concentration of Eletriptan was estimated with the HPLC procedure. In our study Cmax, Tmax, AUC0-24 , AUC0-8, AUC%, AUMC0-24, AUMC0-8, t1/2, MRT0-24, MRT0-8 and Volume of distribution were increased by approximately 51.76%, 7.55%, 72.93%, 84.42%, 42.72%, 93.56%, 128.82%, 19.97%, 11.74%, 23.96% and 3% respectively, where as clearance decreased by 42.10% when eletriptan co-administered with piperine. In summary, the results obtained herein imply that Piperine is improving the bioavailability of Eletriptan by strengthening the exposure (AUC) of their Eletriptan when concomitantly administered by the oral route. The Piperine improved the oral bioavailability of eletriptan by inhibiting CYP3A and P-GP in rats. This observation indicates the possibility that the combo of piperine along with other CYP3A and P-GP double substrates can also enhance bioavailability.

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Repercussion of piperine on pharmacokinetics parameters of eletriptan in albino rats: Involvement of CYP3A and P-GP inhibition

International Journal of Research in Pharmaceutical Sciences ◽

10.26452/ijrps.v11i4.4821 ◽

2020 ◽

Vol 11 (4) ◽

pp. 8079-8086

Author(s):

Hematheerthani N ◽

Siva Reddy CH ◽

Prameela Rani A ◽

Suresh Kumar P

Keyword(s):

Plasma Concentration ◽

Drug Metabolism ◽

Oral Bioavailability ◽

Volume Of Distribution ◽

Oral Route ◽

Severe Headache ◽

Albino Rats ◽

Time Points ◽

P Glycoprotein ◽

Cytochrome P 450

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Increased Oral Bioavailability of Topotecan in Combination With the Breast Cancer Resistance Protein and P-Glycoprotein Inhibitor GF120918

Journal of Clinical Oncology ◽

10.1200/jco.2002.12.116 ◽

2002 ◽

Vol 20 (13) ◽

pp. 2943-2950 ◽

Cited By ~ 309

Author(s):

C. M.F. Kruijtzer ◽

J. H. Beijnen ◽

H. Rosing ◽

W. W. ten Bokkel Huinink ◽

M. Schot ◽

...

Keyword(s):

Plasma Concentration ◽

Oral Bioavailability ◽

Breast Cancer Resistance Protein ◽

Maximum Plasma ◽

Cancer Resistance ◽

P Glycoprotein ◽

Resistance Protein ◽

The Mean ◽

Apparent Bioavailability ◽

Oral Topotecan

PURPOSE: We discovered that breast cancer resistance protein (BCRP), a recently identified adenosine triphosphate–binding cassette drug transporter, substantially limits the oral bioavailability of topotecan in mdr1a/1b(−/−) P-glycoprotein (P-gp) knockout and wild-type mice. GF120918 is a potent inhibitor of BCRP and P-gp. The aim was to increase the bioavailability of topotecan by GF120918. PATIENTS AND METHODS: In cohort A, eight patients received 1.0 mg/m2 oral topotecan with or without coadministration of one single oral dose of 1,000 mg GF120918 (day 1 or day 8). In cohort B, eight other patients received 1.0 mg/m2 intravenous topotecan with or without 1,000 mg oral GF120918 to study the effect of GF120918 on the systemic clearance of topotecan. RESULTS: After oral topotecan, the mean area under the plasma concentration-time curve (AUC) of total topotecan increased significantly from 32.4 ± 9.6 μg·h/L without GF120918 to 78.7 ± 20.6 μg·h/L when GF120918 was coadministered (P = .008). The mean maximum plasma concentration of total topotecan increased from 4.1 ± 1.5 μg/L without GF120918 to 11.5 ± 2.4 μg/L with GF120918 (P = .008). The apparent bioavailability in this cohort increased significantly from 40.0% (range, 32% to 47%) to 97.1% (range, 91% to 120%) (P = .008). Interpatient variability of the apparent bioavailability was 17% without and 11% with GF120918. After intravenous administration of topotecan, coadministration of oral GF120918 had a small but statistically significant effect on the AUC and systemic clearance of total topotecan but no statistically significant effect on maximum plasma concentration and terminal half-life of total topotecan. CONCLUSION: Coadministration of the BCRP and P-gp inhibitor GF120918 resulted in a significant increase of the systemic exposure of oral topotecan. The apparent oral bioavailability increased from 40.0% without to 97.1% with GF120918.

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Enhanced oral bioavailability of linagliptin by the influence of gallic acid and ellagic acid in male Wistar albino rats: involvement of p-glycoprotein inhibition

Drug Metabolism and Personalized Therapy ◽

10.1515/dmpt-2018-0020 ◽

2019 ◽

Vol 34 (2) ◽

Cited By ~ 2

Author(s):

Munthaj Shaik ◽

Swaroopa Rani Vanapatla

Keyword(s):

Serum Concentration ◽

Gallic Acid ◽

Ellagic Acid ◽

Oral Bioavailability ◽

Intestinal Transport ◽

Diabetic Rats ◽

Time Profile ◽

Albino Rats ◽

P Glycoprotein ◽

Oral Pharmacokinetics

Abstract Background Linagliptin is an antidiabetic drug used for the treatment of type-2 diabetes. The oral bioavailability of linagliptin is low (29.5%) due to its first pass metabolism in the intestine and liver. Gallic acid and ellagic acid are natural polyphenols which are widely distributed in fruits and medicinal plants. Gallic acid and ellagic acid have been reported to inhibit p-glycoprotein (p-gp) and enhance the bioavailability of p-gp substrate drugs. Hence, the purpose of the study was to evaluate the effect of gallic acid and ellagic acid on intestinal transport and bioavailability of linagliptin, a p-gp substrate in diabetic rats. Methods The intestinal transport of linagliptin was assessed by conducting an in situ single-pass intestinal perfusion study. The oral pharmacokinetics was evaluated by conducting oral bioavailability study in diabetic rats. Results After pretreatment with gallic acid and ellagic acid, no significant change in effective permeability of linagliptin was observed at the ileum part of the rat intestine. A significant improvement in the peak serum concentration (Cmax) and area under the serum concentration time profile (AUC), AUMC, AUCtotal and decrease in clearance were observed in rats pretreated with gallic acid and ellagic acid. Conclusions This study demonstrates that gallic acid and ellagic acids increase the bioavailability of oral linagliptin in rats due to the inhibition of p-gp. These animal data need to be confirmed in a clinical setting to determine whether linagliptin dosing should be adjusted when given concomitantly with these phytochemicals or gallic acid/ellagic acid-containing dietary supplements.

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Prediction of Tissue to Plasma Concentration Ratios of Drugs in the Rat from Experimentally Estimated Volume of Distribution: Application of Allometry

Current Drug Metabolism ◽

10.2174/1389200219666171129114337 ◽

2018 ◽

Vol 19 (2) ◽

pp. 155-164 ◽

Cited By ~ 1

Author(s):

Iftekhar Mahmood

Keyword(s):

Plasma Concentration ◽

Volume Of Distribution ◽

Concentration Ratios

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Clinical Impact of Co-medication of Levetiracetam and Clobazam with Proton Pump Inhibitors: A Drug Interaction Study

Current Drug Metabolism ◽

10.2174/1389200221666200218121050 ◽

2020 ◽

Vol 21 (2) ◽

pp. 126-131

Author(s):

Bhuvanachandra Pasupuleti ◽

Vamshikrishna Gone ◽

Ravali Baddam ◽

Raj Kumar Venisetty ◽

Om Prakash Prasad

Keyword(s):

Plasma Concentration ◽

Proton Pump Inhibitors ◽

Proton Pump ◽

Plasma Concentrations ◽

Control Group ◽

Drug Concentrations ◽

Significant Difference ◽

Post Hoc ◽

Hydrolysis Of ◽

Cytochrome P 450

Background: Clobazam (CLBZ) metabolized primarily by Cytochrome P-450 isoenzyme CYP3A4 than with CYP2C19, Whereas Levetiracetam (LEV) is metabolized by hydrolysis of the acetamide group. Few CYP enzymes are inhibited by Proton Pump Inhibitors (PPIs) Pantoprazole, Esomeprazole, and Rabeprazole in different extents that could affect drug concentrations in blood. The aim of the present study was to evaluate the effect of these PPIs on the plasma concentrations of LEV and CLBZ. Methods: Blood samples from 542 patients were included out of which 343 were male and 199 were female patients and were categorized as control and test. Plasma samples analyzed using an HPLC-UV method. Plasma concentrations were measured and compared to those treated and those not treated with PPIs. One way ANOVA and games Howell post hoc test used by SPSS 20 software. Results: CLBZ concentrations were significantly 10 folds higher in patients treated with Pantoprazole (P=0.000) and 07 folds higher in patients treated with Esmoprazole and Rabeprazole (P=0.00). Whereas plasma concentration of LEV control group has no statistical and significant difference when compared to pantoprazole (P=0.546) and with rabeprazole and esomeprazole was P=0.999. Conclusion: The effect of comedication with PPIs on the plasma concentration of clobazam is more pronounced for pantoprazole to a greater extent when compared to esomeprazole and rabeprazole. When pantoprazole is used in combination with clobazam, dose reduction of clobazam should be considered, or significance of PPIs is seen to avoid adverse effects.

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Acute and subacute toxicity assessment of Madhulai Manappagu (Siddha herbal syrup formulation) in animal model

Journal of Complementary and Integrative Medicine ◽

10.1515/jcim-2020-0327 ◽

2021 ◽

Vol 0 (0) ◽

Author(s):

Meenakshi Sundaram Malayappan ◽

Gayathri Natarajan ◽

Logamanian Mockaiyathevar ◽

Meenakumari Ramasamy

Keyword(s):

Body Weight ◽

Acute Toxicity ◽

Oral Route ◽

Toxicity Assessment ◽

Toxicity Study ◽

Female Rats ◽

Albino Rats ◽

Oral Toxicity ◽

Gross Pathology ◽

Toxicity Studies

Abstract Objectives Madhulai Manappagu – a well-known sastric and widely prescribed Siddha herbal syrup formulation indicated for treating Veluppu Noi (Anaemia especially Iron deficiency Anaemia) has been in day today practice in Tamil Nadu for a quite longer decades. The syrup is a herbal preparation which has a sweet pleasant odour and a palatable taste, contain the juice of pomegranate (Punica granatum L.) as the main ingredient. Though the formulation is a fruit juice, the safety profile of the syrup is not established and is being marketed without toxicological evaluation. The study is aimed at ascertaining the acute and sub-acute toxicity assessment of Madhulai Manappagu in Wistar Albino rats. Methods The acute and sub-acute (28day repeated oral) toxicity studies were performed as per the guidelines mentioned in the Organization for Economic Cooperation and Development (OECD) 423 (adopted on December 2001) and TG 407 (adopted on October 2008) with slight modifications respectively. For acute toxicity study, three female rats were randomly selected as control; three female rats were randomly selected and were administered a single dose of 5,000 mg/kg body weight per oral route. For sub-acute (28day repeated oral) toxicity studies, three doses of test drug MM of 500 mg/kg/day (low dose), 750 mg/kg/day (intermittent dose) and 1,000 mg/kg/day (high dose) were selected for administration. Both sexes of Wistar Albino rats were randomized into four groups of 10 animals each (five males, five females). Group I was kept as control group. Group II, III and IV served as low, intermittent and high doses of MM respectively. Animals were observed for mortality, morbidity, body weight changes, feed and water intake. Haematology, clinical biochemistry, electrolytes, gross pathology, relative organ weight and histopathological examination were performed. Results In the acute toxicity study, rats showed no toxicological signs on behavior, gross pathology and body weight of rats when treated with a single dose of 5,000 mg/kg body weight per oral route. In the subacute (28 days repeated oral) toxicity study, rats have showed no significant changes on behavior, gross pathology, body weight, and hematological and biochemical parameters when treated with Madhulai Manappagu in three different doses. Conclusions The toxicity studies which include both acute and 28 days repeated (subacute) oral toxicity studies, revealed no observed adverse effect level (NOAEL) of Madhulai Manappagu in animals. Thus the safety of the drug in human usage was ensured.

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Cocaine: Pharmacokinetics and biotransformation in man

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y89-184 ◽

1989 ◽

Vol 67 (9) ◽

pp. 1154-1157 ◽

Cited By ~ 44

Author(s):

T. Inaba

Keyword(s):

Methyl Ester ◽

Ester Group ◽

Oral Route ◽

Plasma Cholinesterase ◽

Pharmacokinetic Studies ◽

Hydrolytic Cleavage ◽

Bicyclic Structure ◽

Anesthetic Action ◽

Pharmacologically Active ◽

Cytochrome P 450

Pharmacokinetic studies of cocaine have been carried out only in the last decade, although its local anesthetic action and addictive properties have been known for almost 100 years. Elimination half-lives of cocaine in man estimated from serial plasma concentration are relatively short and range from 0.5 to 1.1 h after i.v. and 0.9–1.5 h after administration by the nasal or oral route. The bioavailability after nasal inhalation is about 60%. The bicyclic structure of cocaine is characterized by functional groups including N-methyl, carboxyl methyl ester, and benzoyl ester, which are susceptible to biotransformation. Hydrolysis of the benzoyl group to ecgonine methyl ester is catalyzed by plasma cholinesterase and is thus under monogenic control. The hydrolytic cleavage of the other ester group, methyl ester, to benzoyl ecgonine occurs spontaneously at body temperature. In contrast, N-demethylation of cocaine mediated by microsomal cytochrome P-450 produces norcocaine and this metabolite was shown to be pharmacologically active, the action being similar to cocaine.Key words: cocaine, hydrolysis, plasma cholinesterase, cytochrome P-450.

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