Enhanced oral bioavailability of metoprolol with gallic acid and ellagic acid in male Wistar rats: involvement of CYP2D6 inhibition

2016 ◽  
Vol 31 (4) ◽  
Author(s):  
Bhargavi Latha Athukuri ◽  
Prasad Neerati
Keyword(s):  
Drug Interactions ◽  
Gallic Acid ◽  
Ellagic Acid ◽  
Oral Bioavailability ◽  
Peak Plasma ◽  
Peak Plasma Concentration ◽  
Intestinal Transport ◽  
Herbal Drug ◽  
Male Wistar Rats ◽  
Mixed Function Oxidase System

Abstract Background: Cytochrome P450-2D6 (CYP2D6), a member of the CYP450 mixed function oxidase system, is an important CYP isoform with regard to herbal-drug interactions and is responsible for the metabolism of nearly 25% of drugs. Until now, studies on the effects of various phytochemicals on CYP2D6 activity Methods: The intestinal transport of metoprolol was assessed by conducting an Results: After pretreatment with gallic acid and ellagic acid, no significant change in effective permeability of metoprolol was observed at the ileum part of rat intestine. A significant improvement in the peak plasma concentration (C Conclusions: Gallic acid and ellagic acid significantly enhanced the oral bioavailability of metoprolol by inhibiting CYP2D6-mediated metabolism in the rat liver. Hence, adverse herbal-drug interactions may result with concomitant ingestion of gallic acid and ellagic acid supplements and drugs that are CYP2D6 substrates. The clinical assessment of these interactions should be further investigated in human volunteers.

scholarly journals Enhanced Oral Bioavailability of Domperidone with Piperine in Male Wistar Rats: Involvement of CYP3A1 and P-gp Inhibition

2017 ◽  
Vol 20 ◽  
pp. 28 ◽  
Author(s):  
Bhargavi Latha Athukuri ◽  
Prasad Neerati
Keyword(s):  
Plasma Concentration ◽  
Oral Bioavailability ◽  
Wistar Rats ◽  
Peak Plasma ◽  
Peak Plasma Concentration ◽  
Elimination Rate ◽  
Intestinal Transport ◽  
Control Group ◽  
Maximum Plasma ◽  
Male Wistar Rats

Purpose: Domperidone is a commonly used antiemetic drug. The oral bioavailability of domperidone is very low due to its rapid first pass metabolism in the intestine and liver. Piperine, the main alkaloid present in black pepper has been reported to show inhibitory effects on Cytochrome P-450 (CYP-450) enzymes and P-glycoprotein (P-gp). In the present study we investigated the effect of piperine pretreatment on the intestinal transport and oral bioavailability of domperidone in male Wistar rats. Methods: The intestinal transport of domperidone was evaluated by an in-vitro non-everted sac method and in-situ single pass intestinal perfusion (SPIP) study. The oral pharmacokinetics of domperidone was evaluated by conducting oral bioavailability study in rats. Results: A statistically significant improvement in apparent permeability (Papp) was observed in rats pretreated with piperine compared to the respective control group. The effective permeability (Peff) of domperidone was increased in the ileum of the piperine treated group. Following pretreatment with piperine, the peak plasma concentration (Cmax) and area under the concentration- time curve (AUC) were significantly increased. A significant decrease in time to reach maximum plasma concentration (Tmax), clearance and elimination rate constant (Kel) was observed in rats pretreated with piperine. Conclusions: Piperine enhanced the oral bioavailability of domperidone by inhibiting CYP3A1 and P-gp in rats. This observation suggests the possibility that the combination of piperine with other CYP3A4 and P-gp dual substrates may also improve bioavailability. Further clinical studies are recommended to verify this drug interaction in human volunteers and patients. This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.

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

2019 ◽  
Vol 34 (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.

Pharmacokinetics of solid lipid Boswellia serrata particles in healthy subjects

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Preeti D. Kulkarni ◽  
Neena D. Damle ◽  
Lal Hingorani ◽  
Vaidhun H. Bhaskar ◽  
Minal R. Ghante ◽  
...  
Keyword(s):  
Plasma Concentration ◽  
Oral Bioavailability ◽  
Peak Plasma ◽  
Peak Plasma Concentration ◽  
Maximum Plasma ◽  
Boswellic Acid ◽  
Healthy Human ◽  
Boswellia Serrata ◽  
Solid Lipid ◽  
Human Volunteers

Abstract Objectives The anti-inflammatory activity of Boswellia serrata extracts (BSE) is well known. BSE comprises boswellic acids (BA) such as 3-O-acetyl-11-keto-beta-boswellic acid (AKBA) and 11-keto-boswellic acid (KBA) as major constituents. One of the limitations of BAs is their poor oral bioavailability. The aim of the study was to prepare solid lipid particles of Boswellia serrata extract (SLBSP) to enhance the bioavailability of BAs. Methods The pharmacokinetic profile of BAs was studied in 10 healthy human volunteers following a single oral dose of 333 mg of SLBSP. Pharmacokinetic blood samples were collected at 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, and 12 h post drug administration. Plasma KBA and AKBA levels were measured using a validated LC-MS/MS method. Pharmacokinetics parameters were estimated using Pheonix WinNonlin (Build 6.4.0.768) software. Results Ten healthy human volunteers were included and peak plasma concentration was achieved in 1.5 and 2.3 h for AKBA and KBA respectively. Maximum plasma concentration (C max) was 8.04 ± 1.67 ng/mL for AKBA and 23.83 ± 4.41 ng/mL for KBA whereas the corresponding area under the concentration-time curve (AUC) was 136.7 ± 56.77 ng/mL*h and 165.7 ± 24.5 ng/mL*h respectively. The elimination half-life (t 1/2) of AKBA and KBA was 6.8 ± 3.0 h and 2.45 ± 0.3 h respectively. Conclusions The SLBSP formulation of BSE showed enhanced oral bioavailability of BAs compared with historically reported data of unformulated BSE.

Pharmacokinetics of solid lipid Boswellia serrata particles in healthy subjects

2021 ◽  
Vol 36 (3) ◽  
pp. 215-221
Author(s):  
Preeti D. Kulkarni ◽  
Neena D. Damle ◽  
Lal Hingorani ◽  
Vaidhun H. Bhaskar ◽  
Minal R. Ghante ◽  
...  
Keyword(s):  
Plasma Concentration ◽  
Oral Bioavailability ◽  
Peak Plasma ◽  
Peak Plasma Concentration ◽  
Maximum Plasma ◽  
Boswellic Acid ◽  
Healthy Human ◽  
Boswellia Serrata ◽  
Solid Lipid ◽  
Human Volunteers

Abstract Objectives The anti-inflammatory activity of Boswellia serrata extracts (BSE) is well known. BSE comprises boswellic acids (BA) such as 3-O-acetyl-11-keto-beta-boswellic acid (AKBA) and 11-keto-boswellic acid (KBA) as major constituents. One of the limitations of BAs is their poor oral bioavailability. The aim of the study was to prepare solid lipid particles of Boswellia serrata extract (SLBSP) to enhance the bioavailability of BAs. Methods The pharmacokinetic profile of BAs was studied in 10 healthy human volunteers following a single oral dose of 333 mg of SLBSP. Pharmacokinetic blood samples were collected at 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, and 12 h post drug administration. Plasma KBA and AKBA levels were measured using a validated LC-MS/MS method. Pharmacokinetics parameters were estimated using Pheonix WinNonlin (Build 6.4.0.768) software. Results Ten healthy human volunteers were included and peak plasma concentration was achieved in 1.5 and 2.3 h for AKBA and KBA respectively. Maximum plasma concentration (C max) was 8.04 ± 1.67 ng/mL for AKBA and 23.83 ± 4.41 ng/mL for KBA whereas the corresponding area under the concentration-time curve (AUC) was 136.7 ± 56.77 ng/mL*h and 165.7 ± 24.5 ng/mL*h respectively. The elimination half-life (t 1/2) of AKBA and KBA was 6.8 ± 3.0 h and 2.45 ± 0.3 h respectively. Conclusions The SLBSP formulation of BSE showed enhanced oral bioavailability of BAs compared with historically reported data of unformulated BSE.

scholarly journals TO STUDY THE PHARMACOKINETIC HERB-DRUG INTERACTION OF MOMORDICA CHARANTIA FRUIT EXTRACT AND PURE CHARANTIN WITH NATEGLINIDE IN RATS

2021 ◽  
pp. 1-5
Author(s):  
AISHWARYA R. BALAP
Keyword(s):  
Drug Interaction ◽  
Plasma Concentration ◽  
Drug Interactions ◽  
Peak Plasma ◽  
Peak Plasma Concentration ◽  
Systemic Exposure ◽  
Momordica Charantia ◽  
Exposure Level ◽  
Fruit Extract

Objective: Momordica charantia fruit extract and antidiabetic drug Nateglinide might be used simultaneously in the treatment of diabetes, so the objective of this study was to investigate pharmacokinetic herb-drug interactions of Momordica charantia fruit extract and pure charantin with nateglinide in rats. Methods: After oral co-administration of Momordica charantia fruit extract (250 mg/kg) and Charantin (10 mg/kg) with nateglinide in rats, drug concentration parameters peak plasma concentration (Cmax), time to reach peak plasma concentration (tmax), elimination half-life (t1/2), apparent volume of distribution (Vd), plasma clearance (Cl), and area under the curve (AUC) were calculated by using the non-compartment model. Results: NAT was absorbed into the circulatory system and reached its peak concentration approximately 2 h after being administered individually. tmax of groups co-administered NAT+MCE has been changed to 4h. A significant decrease in Cmax of NAT from 16.28 µg/ml to 11.37 µg/ml and 10.37 µg/ml with NAT with charantin and NAT with MCE groups, respectively. AUC of NAT decreased from 84.53 h/µg/ml to 53.63 h/µg/ml and 47.17 h/µg/ml by co-administration with Charantin and MCE respectively. Co-administration of nateglinide with Charantin and Momordica charantia fruit extract decreased systemic exposure level of nateglinide in vivo with decreasing Cmax and AUC and an increase in t1/2, Cl and Vd. Conclusion: From this study, it can be concluded that nateglinide, Momordica charantia fruit extract, and pure Charantin existed pharmacokinetic herb-drug interactions in the rat which has to be correlated with the anti-diabetic study. Further studies should be done to understand the effect of other herbal ingredients of Momordica charantia fruit extract on nateglinide as well as to predict the herb-drug interaction in humans.

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.

Phytochemical Investigation and Antimutagenic Potential of Ethanolic Extracts of Emblica officinalis, Terminalia chebula and Terminalia bellirica

2020 ◽  
Vol 10 (4) ◽  
pp. 488-494 ◽  
Author(s):  
Venugopal Singamaneni ◽  
Sudheer Kumar Dokuparthi ◽  
Nilanjana Banerjee ◽  
Ashish Kumar ◽  
Tulika Chakrabarti
Keyword(s):  
Ethyl Acetate ◽  
Gallic Acid ◽  
Ellagic Acid ◽  
Antimutagenic Activity ◽  
Dependent Manner ◽  
Terminalia Chebula ◽  
Emblica Officinalis ◽  
Dried Fruits ◽  
Terminalia Bellerica ◽  
The Family

Background: Emblica officinalis Gaertn. which belongs to the family Euphorbiaceae, Terminalia chebula Retz. and Terminalia bellerica Roxb. belong to the family Combretaceae. These are well known medicinal plants with phytochemical reservoir of great medicinal values and possess a vast ethnomedical history. Objective: The aim of the present study is to isolation of major compounds and to evaluate antimutagenic potential of the ethanol extracts of these plants. Methods: The dried fruits of E. officinalis, T. bellirica and T. chebula were powdered and extracted with 95% ethanol. The ethyl acetate portions were chromatographed over silica gel to isolate major compounds. Antimutagenic activity was determined by Ames test using TA98 and TA100 strains of Salmonella typhimurium. Results: Two major known compounds, gallic acid and ellagic acid were isolated from the dried fruits of Emblica officinalis, Terminalia chebula and T. bellirica. All the three extracts counteracted the mutagenicity induced by different genotoxic compounds in a dose dependent manner. Conclusion: This study showed that ethyl acetate portion of three extracts contain two major compounds, gallic acid and ellagic acid which might be responsible for potent antimutagenic activity of these extracts.

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