scholarly journals Acute and Chronic Toxicity, Cytochrome P450 Enzyme Inhibition, and hERG Channel Blockade Studies with a Polyherbal, Ayurvedic Formulation for Inflammation

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Debendranath Dey ◽  
Sunetra Chaskar ◽  
Nitin Athavale ◽  
Deepa Chitre
Keyword(s):  
Cytochrome P450 ◽  
Radioligand Binding ◽  
Curcuma Longa ◽  
Raw 264.7 Cells ◽  
Cytochrome P450 Enzyme ◽  
Sprague Dawley ◽  
Cytochrome P450 Enzymes ◽  
Boswellia Serrata ◽  
Cell Counts ◽  
Anti Inflammatory

Ayurvedic plants are known for thousands of years to have anti-inflammatory and antiarthritic effect. We have recently shown that BV-9238, a proprietary formulation ofWithania somnifera, Boswellia serrata, Zingiber officinale,andCurcuma longa,inhibits LPS-induced TNF-alpha and nitric oxide production from mouse macrophage and reduces inflammation in different animal models. To evaluate the safety parameters of BV-9238, we conducted a cytotoxicity study in RAW 264.7 cells (0.005–1 mg/mL) by MTT/formazan method, an acute single dose (2–10 g/kg bodyweight) toxicity study and a 180-day chronic study with 1 g and 2 g/kg bodyweight in Sprague Dawley rats. Some sedation, ptosis, and ataxia were observed for first 15–20 min in very high acute doses and hence not used for further chronic studies. At the end of 180 days, gross and histopathology, blood cell counts, liver and renal functions were all at normal levels. Further, a modest attempt was made to assess the effects of BV-9238 (0.5 µg/mL) on six major human cytochrome P450 enzymes and3H radioligand binding assay with human hERG receptors. BV-9238 did not show any significant inhibition of these enzymes at the tested dose. All these suggest that BV-9238 has potential as a safe and well tolerated anti-inflammatory formulation for future use.

Novel Metabolic Bioactivation Mechanism for a Series of Anti-Inflammatory Agents (2,5-Diaminothiophene Derivatives) Mediated by Cytochrome P450 Enzymes

2010 ◽  
Vol 38 (9) ◽  
pp. 1522-1531 ◽  
Author(s):  
Yiding Hu ◽  
Shengtian Yang ◽  
F. Barclay Shilliday ◽  
Bruce R. Heyde ◽  
Kathy M. Mandrell ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Cytochrome P450 Enzymes ◽  
Anti Inflammatory

Drug Interactions of Macrolides: Emphasis on Dirithromycin

1997 ◽  
Vol 31 (3) ◽  
pp. 349-356 ◽  
Author(s):  
Vish S Watkins ◽  
Ron E Polk ◽  
Jennifer L Stotka
Keyword(s):  
Cytochrome P450 ◽  
Drug Interactions ◽  
Ethinyl Estradiol ◽  
Enzyme System ◽  
Cytochrome P450 Enzyme ◽  
Cytochrome P450 Enzymes ◽  
Kidney Transplant Recipients ◽  
P450 Enzyme ◽  
Cytochrome P450 Enzyme System ◽  
Clinically Significant

Objective To describe the drug interactions of dirithromycin, a new macrolide, and to compare them with those of other macrolides. Data Sources A literature search was performed using MEDLINE to identify articles published between January 1980 and July 1995 concerning the drug interactions of macrolides. Published abstracts were also examined. All studies using dirithromycin were performed under the sponsorship of Eli Lilly and Company. Data Synthesis Erythromycin, the first macrolide discovered, is metabolized by the cytochrome P450 enzyme system. By decreasing their metabolism, erythromycin can interact with other drugs metabolized by the cytochrome P450 enzymes. The lack of such interactions would be a desirable feature in a newer macrolide. We describe studies performed to detect any interactions of dirithromycin with cyclosporine, theophylline, terfenadine, warfarin, and ethinyl estradiol. The studies showed that dirithromycin, like azithromycin, is much less likely to cause the interactions detected with clarithromycin and erythromycin. A review of the literature showed differences among macrolides in their abilities to inhibit cytochrome P450 enzymes and, thus, to cause drug–drug interactions. Erythromycin and clarithromycin inhibit cytochrome P450 enzymes, and have been implicated in clinically significant interactions. Azithromycin and dirithromycin neither inhibit cytochrome P450 enzymes nor are implicated in clinically significant drug–drug interactions. Conclusions Dirithromycin, a new macrolide, does not inhibit the cytochrome P450 enzyme system. The concomitant use of dirithromycin with cyclosporine, theophylline, terfenadine, warfarin, or ethinyl estradiol was studied in pharmacokinetic and pharmacodynamic studies. In vitro, dirithromycin did not bind cytochrome P450. In healthy subjects, erythromycin increases the clearance of cyclosporine by 51%, whereas dirithromycin causes no significant changes in the pharmacokinetics of cyclosporine. In kidney transplant recipients, administration of dirithromycin was associated with a significant (p < 0.003) decrease of 17.4% in the clearance of cyclosporine. In patients taking low-dose estradiol, the administration of dirithromycin caused a significant (p < 0.03) increase of 9.9% in the clearance of ethinyl estradiol; escape ovulation did not occur. Unlike erythromycin and clarithromycin, dirithromycin had no significant effects on the pharmacokinetics of theophylline, terfenadine, or warfarin. The alterations typical of drug interactions that are based on inhibition of the cytochrome P450 system occurring with erythromycin and clarithromycin were not observed with dirithromycin.

scholarly journals An Anti-Inflammatory Composition of Boswellia serrata Resin Extracts Alleviates Pain and Protects Cartilage in Monoiodoacetate-Induced Osteoarthritis in Rats

2020 ◽  
Vol 2020 ◽  
pp. 1-12
Author(s):  
Venkata Krishnaraju Alluri ◽  
Sreenath Kundimi ◽  
Krishanu Sengupta ◽  
Trimurtulu Golakoti ◽  
Eswar Kumar Kilari
Keyword(s):  
Articular Cartilage ◽  
Structural Damage ◽  
Weight Bearing ◽  
Prostaglandin E ◽  
Thermal Stimulus ◽  
Sprague Dawley ◽  
Boswellia Serrata ◽  
Anti Inflammatory ◽  
Safranin O ◽  
Unique Composition

The boswellic acids, the active compounds in Boswellia serrata gum resin extract, are potent anti-inflammatory agents and are specific nonredox inhibitors of 5-Lipoxygenase (5-LOX). Here, we present the anti-osteoarthritis (OA) efficacy of LI13019F1 (also known as Serratrin®), a unique composition containing the acidic and nonacidic fractions of B. serrata gum resin. This composition strongly inhibited 5-LOX activity with the half-maximal inhibitory concentration (IC50) of 43.35 ± 4.90 μg/mL. Also, LI13019F1 strongly inhibited the leukotriene B4 (IC50, 7.80 ± 2.40 μg/mL) and prostaglandin E2 (IC50, 6.19 ± 0.52 μg/mL) productions in human blood-derived cells. Besides, LI13019F1 reduced TNF-α production with the IC50 of 12.38 ± 0.423 μg/mL. On average, 1, 2.5, and 5 μg/mL doses of LI13019F1 protected 34.62, 47.66, and 62.29% SW1353 human chondrosarcoma cells from IL-1β induced SOX-9 depletion, respectively. Further, a 28-day preclinical proof-of-concept study evaluated the pain relief efficacy of LI13019F1 in monoiodoacetate- (MIA-) induced Sprague-Dawley rats. At the end of the study, 150 and 300 mg/kg doses of LI13019F1 supplemented rats showed significant improvements (55.17 ± 5.81 g (p<0.05), and 66.22 ± 6.30 g (p<0.05), respectively, vs. MIA: 31.22 ± 7.15 g) in body-weight-bearing capacities. Concurrently, LI13019F1-150 and LI13019F1-300 rats substantially (p<0.05) increased the threshold of pain sensitivity to pressure (26.98 ± 2.36 and 28.06 ± 2.72-gram force, respectively; vs. 18.63 ± 5.82 in MIA) and increased (p<0.05) the latent time to withdraw the paw after a thermal stimulus (23.61 ± 2.73 and 28.18 ± 1.90 sec, respectively; vs. 16.56 ± 1.22 sec. in MIA). Besides, the histological observations on Safranin-O green stained articular cartilage revealed that LI13019F1 also prevented the MIA-induced structural damage of the cartilage and reduced the loss of the extracellular matrix (ECM) components in the experimental rats. In conclusion, the present observations suggest that LI13019F1, a new composition of B. serrata gum resin extracts, reduces pain and protects articular cartilage from the damaging action of MIA in a rodent model.

scholarly journals Activation of cholinergic anti-inflammatory pathway involved in therapeutic actions of α-mangostin on lipopolysaccharide-induced acute lung injury in rats

2020 ◽  
Vol 34 ◽  
pp. 205873842095494
Author(s):  
Zhe Yang ◽  
Qin Yin ◽  
Opeyemi Joshua Olatunji ◽  
Yan Li ◽  
Shu Pan ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Raw 264.7 Cells ◽  
Raw 264.7 ◽  
Sprague Dawley ◽  
Α7 Nicotinic Acetylcholine Receptor ◽  
Inflammatory Pathway ◽  
Inflammatory Reactions ◽  
Sprague Dawley Rats ◽  
Anti Inflammatory

Introduction: Alpha-mangostin (MAN) possesses a wide variety of pharmacological effects. In this study, we investigated its effect on cholinergic anti-inflammatory pathway (CAP), and tested if CAP regulation was involved in the therapeutic action on acute lung injury (ALI). Methods: Male Sprague Dawley rats were pre-treated with MAN (40 mg/kg) for 3 days and ALI was induced with an intraperitoneal injection of lipopolysaccharide (LPS). Certain rats received monolateral vagotomy or sham surgery. The effects on inflammatory reactions and relevant pathways in ALI rats or LPS pre-treated RAW 264.7 cells were investigated by histological, immunohistochemical, immunoblotting, RT-qPCR, and immunofluorescence assays, while levels of proinflammatory cytokines, acetylcholine (Ach) and the enzymatic activity of acetylcholinesterase (AchE) were determined by corresponding quantitative kits. Results: Oral administration of MAN reduced the severity of ALI, while vagotomy surgery antagonized this effect. MAN restored the decline in α7 nicotinic acetylcholine receptor (α7nAchR) in the lungs of ALI rats, and promoted the expression of α7nAchR and choline acetyltransferase (CHAT) in RAW 264.7 cells. Although AchE expression was barely affected by MAN at 5 μg/ml, its catalytic activity was reduced by almost 95%. Extracellular rather than intracellular Ach was notably raised shortly after MAN treatment. Furthermore, MAN at 5 μg/ml effectively inhibited LPS-induced increase in phosphorylation and nucleus translocation of p65 subunit, and secretion of TNF-α and IL-1β, which was then offset by methyllycaconitine citrate hydrate. Conclusion: MAN activated CAP by increasing peripheral Ach and up-regulating α7nAchR expression, which eventually led to NF-κB inhibition and remission of acute inflammations.

scholarly journals Characterization of Medicago truncatula (barrel medic) hydroperoxide lyase (CYP74C3), a water-soluble detergent-free cytochrome P450 monomer whose biological activity is defined by monomer–micelle association

2006 ◽  
Vol 395 (3) ◽  
pp. 641-652 ◽  
Author(s):  
Richard K. Hughes ◽  
Eric J. Belfield ◽  
Mylrajan Muthusamay ◽  
Anuja Khan ◽  
Arthur Rowe ◽  
...  
Keyword(s):  
Enzyme Activity ◽  
Cytochrome P450 ◽  
Medicago Truncatula ◽  
Water Soluble ◽  
Hydroperoxide Lyase ◽  
Cytochrome P450 Enzyme ◽  
Cytochrome P450 Enzymes ◽  
P450 Enzyme ◽  
Detergent Micelles

We describe the detailed biochemical characterization of CYP74C3 (cytochrome P450 subfamily 74C3), a recombinant plant cytochrome P450 enzyme with HPL (hydroperoxide lyase) activity from Medicago truncatula (barrel medic). Steady-state kinetic parameters, substrate and product specificities, RZ (Reinheitszahl or purity index), molar absorption coefficient, haem content, and new ligands for an HPL are reported. We show on the basis of gel filtration, sedimentation velocity (sedimentation coefficient distribution) and sedimentation equilibrium (molecular mass) analyses that CYP74C3 has low enzyme activity as a detergent-free, water-soluble, monomer. The enzyme activity can be completely restored by re-activation with detergent micelles, but not detergent monomers. Corresponding changes in the spin state equilibrium, and probably co-ordination of the haem iron, are novel for cytochrome P450 enzymes and suggest that detergent micelles have a subtle effect on protein conformation, rather than substrate presentation, which is sufficient to improve substrate binding and catalytic-centre activity by an order of magnitude. The kcat/Km of up to 1.6×108 M−1·s−1 is among the highest recorded, which is remarkable for an enzyme whose reaction mechanism involves the scission of a C–C bond. We carried out both kinetic and biophysical studies to demonstrate that this effect is a result of the formation of a complex between a protein monomer and a single detergent micelle. Association with a detergent micelle rather than oligomeric state represents a new mechanism of activation for membrane-associated cytochrome P450 enzymes. Highly concentrated and monodispersed samples of detergent-free CYP74C3 protein may be well suited for the purposes of crystallization and structural resolution of the first plant cytochrome P450 enzyme.

scholarly journals Bioactivity of curcumin on the cytochrome P450 enzymes of the steroidogenic pathway

2019 ◽  
Author(s):  
Patricia Rodríguez Castaño ◽  
Shaheena Parween ◽  
Amit V Pandey
Keyword(s):  
Cytochrome P450 ◽  
Active Sites ◽  
Curcuma Longa ◽  
Docking Studies ◽  
Steroid Metabolism ◽  
Dependent Manner ◽  
Cytochrome P450 Enzymes ◽  
Lead Compounds ◽  
Anti Cancer ◽  
Mild Reduction

AbstractTurmeric, a popular ingredient in the cuisine of many Asian countries, comes from the roots of theCurcuma longaand is known for its use in Chinese and Ayurvedic medicine. Turmeric is rich in curcuminoids, including curcumin, demethoxycurcumin, and bisdemethoxycurcumin. Curcuminoids have potent wound healing, anti-inflammatory, and anti-carcinogenic activities. While curcuminoids have been studied for many years, not much is known about their effects on steroid metabolism. Since many anti-cancer drugs target enzymes from the steroidogenic pathway, we tested the effect of curcuminoids on cytochrome P450 CYP17A1, CYP21A2, and CYP19A1 enzyme activities. When using 10 µg/ml of curcuminoids, both the 17α-hydroxylase as well as 17,20 lyase activities of CYP17A1 were reduced significantly. On the other hand, only a mild reduction in CYP21A2 activity was observed. Furthermore, CYP19A1 activity was also reduced up to ~20% of control when using 1-100 µg/ml of curcuminoids in a dose-dependent manner. Molecular docking studies confirmed that curcumin could dock into the active sites of CYP17A1, CYP19A1 as well as CYP21A2. In CYP17A1 and CYP19A1, curcumin docked within 2.5 Å of central heme while in CYP21A2 the distance from heme was 3.4 Å, which is still in the same range or lower than distances of bound steroid substrates. These studies suggest that curcuminoids may cause inhibition of steroid metabolism, especially at higher dosages. Also, the recent popularity of turmeric powder as a dilatory supplement needs further evaluation for the effect of curcuminoids on steroid metabolism. Molecular structure of curcuminoids could be modified to generate better lead compounds with inhibitory effects on CYP17A1 and CYP19A1 for potential drugs against prostate cancer and breast cancer.

Inhibitory Effects of Garcinia cambogia Extract on CYP2B6 Enzyme Activity

Planta Medica ◽  
2017 ◽  
Vol 83 (11) ◽  
pp. 895-900 ◽  
Author(s):  
Jun Yu ◽  
Min Choi ◽  
Jong Park ◽  
Shaheed Rehman ◽  
Katsunori Nakamura ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Enzyme Activities ◽  
Liver Microsomes ◽  
Cytochrome P450 Enzyme ◽  
Dependent Manner ◽  
Cytochrome P450 Enzymes ◽  
Inhibitory Effects ◽  
Concentration Dependent Manner ◽  
Garcinia Cambogia ◽  
P450 Enzyme

AbstractThis study assessed the inhibitory effects of Garcinia cambogia extract on the cytochrome P450 enzymes in vitro. G. cambogia extract was incubated with cytochrome P450 isozyme-specific substrates in human liver microsomes and recombinant CYP2B6 isozyme, and the formation of the marker metabolites was measured to investigate the inhibitory potential on cytochrome P450 enzyme activities. The results showed that G. cambogia extract has significant inhibitory effects on CYP2B6 activity in a concentration-dependent manner. Furthermore, the inhibition was potentiated following preincubation with NADPH, indicating that G. cambogia extract is a time-dependent inhibitor of CYP2B6. Meanwhile, hydroxycitric acid, the major bioactive ingredient of G. cambogia extract, did not exhibit significant inhibition effects on cytochrome P450 enzyme activities. G. cambogia extract could modulate the pharmacokinetics of CYP2B6 substrate drugs and lead to interactions with those drugs. Therefore, caution may be required with respect to concomitant intake of dietary supplements containing G. cambogia extract with CYP2B6 substrates.

scholarly journals Efektivitas Pemberian Biocurpain untuk Memperbaiki Status Fungsional pada Pasien Osteoarthritis

2020 ◽  
Vol 7 (1) ◽  
pp. 51
Author(s):  
Rizaldy Taslim Pinzon ◽  
Eric Eric
Keyword(s):  
Randomized Control Trial ◽  
Rescue Medication ◽  
Curcuma Longa ◽  
Boswellia Serrata ◽  
Inflammatory Drugs ◽  
Randomized Control ◽  
Anti Inflammatory ◽  
Lost To Follow Up

Pendahuluan: Osteoarthritis (OA) merupakan penyakit radang sendi progresif yang menurunkan kualitas hidup. Penyakit ini tidak dapat disembuhkan dan terbatas hanya mengurangi nyeri yang dialami oleh pasien. Obat yang sering digunakan adalah non-steroidal anti-inflammatory drugs (NSAIDs), namun penggunaan obat tersebut tidak terlepas dari efek samping jika digunakan dalam jangka panjang. Maka diperlukan obat yang efektif dan aman untuk memperbaiki status fungsional pada pasien osteoarthritis. Tujuan: membandingkan efektifitas dari pemberian Biocurpain yang memiliki Nomor Izin Edar (NIE) TR172599281 dengan NSAIDs untuk memperbaiki status fungsional pada terapi pasien OA. Metode: Penelitian ini menggunakan metode Randomized Control Trial (RCT) yang melibatkan pasien OA. Perlakuan yang diberikan berupa Biocurpain (Curcuma longa 300 mg dan Boswellia serrata 150 mg) dan NSAIDs (ibuprofen 400 mg). Subjek diacak menjadi 2 kelompok (kelompok 1 memperoleh Biocurpain dan kelompok 2 memperoleh NSAIDs). Pengukuran status fungsional menggunakan Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Hasil: Terdapat 67 subjek yang mengikuti penelitian ini, 5 subjek lost to follow up dan 3 subjek tidak dapat melanjutkan penelitian karena efek samping yang dirasakan. Sebanyak 59 subjek mengikuti penelitian hingga selesai (kelompok 1 berisi 29 subjek dan kelompok 2 berisi 30 subjek). Tidak ada perbedaan yang signifikan antar kelompok dalam memperbaiki status fungsional (p: 0,771), penggunaan rescue medication (p: 0,370), kejadian efek samping pada visit II (0,215) dan visit III (0,537) pada subjek OA. Kelompok 2 menunjukkan lebih banyak subjek yang mengalami efek samping. Kesimpulan: Biocurpain memiliki efektivitas yang setara dengan NSAIDs dalam memperbaiki status fungsional pada pasien OA.

Effect of Cellgevity® Supplement on Selected Rat Liver Cytochrome P450 Enzyme Activity and Pharmacokinetic Parameters of Carbamazepine

2020 ◽  
Author(s):  
Seth Kwabena Amponsah ◽  
Benoit Banga Nguessan ◽  
Martin Akandawen ◽  
Abigail Aning ◽  
Sedem Yawa Agboli ◽  
...  
Keyword(s):  
Enzyme Activity ◽  
Cytochrome P450 ◽  
Rat Liver ◽  
Normal Saline ◽  
Pharmacokinetic Parameters ◽  
Cytochrome P450 Enzyme ◽  
Sprague Dawley ◽  
Serum Samples ◽  
Liver Cytochrome ◽  
Sd Rats

Abstract Background: There is considerable evidence that many patients concurrently administer dietary supplements with conventional drugs, creating a risk for potential drug-supplement interaction. The aim of this study was to determine the effect of Cellgevity® supplement on selected rat liver cytochrome P450 (CYP) enzymes. Also, we sought to deternine the effect of Cellgevity® on the pharmacokinetics of carbamazepine, a CYP3A4 substrate. Methods: Male Sprague-Dawley (SD) rats were randomly put into 5 groups and administered (per os) either distilled water (negative control), Cellgevity® (3 separate doses) or phenobarbital (positive control). Modulation of liver CYP enzyme activity was evaluated after 30 days of treatment, using probe substrates, spectroscopic and high-performance liquid chromatographic methods. In the pharmacokinetic study, 12 SD rats were divided into 2 groups administered (per os) carbamazepine plus Cellgevity®, or carbamazepine plus normal saline, both over a period of 14 days. Blood samples from rats in the same group were collected after treatment. Serum samples were prepared and pooled together at each specific sampling time point. Levels of carbamazepine were determined using a fluorescence polarization immunoassay. Results: Activities of rat liver CYP1A1/2, CYP2C9 and CYP2D6 were significantly increased by Cellgevity® after 30-day treament. Pharmacokinetic parameters for rats administered carbamazepine with Cellgevity® vis-a-vis carbamazepine with normal saline were as follows: Cmax; 20 μmol/L vs 11 μmol/L, AUC0→24; 347 μmol.h/L vs 170 μmol.h/L, Ke; 0.28 h-1 vs 0.41 h-1, and t1/2; 2.3 h vs 1.7 h, respectively.Conclusions: Cellgevity® increased the activity of rat CYP1A1/2, CYP2C9 and CYP2D6 enzymes, and altered the pharmacokinetics of carbamazepine in rats.

Effect Of 30-Day Administration Of Cellgevity® Supplement On Selected Rat Liver Cytochrome P450 Enzyme Activity And Supplement Interaction With Carbamazepine

2019 ◽  
Author(s):  
Seth Kwabena Amponsah ◽  
Benoit Banga Nguessan ◽  
Martin Akandawen ◽  
Abigail Aning ◽  
Sedem Yawa Agboli ◽  
...  
Keyword(s):  
Enzyme Activity ◽  
Cytochrome P450 ◽  
Rat Liver ◽  
Normal Saline ◽  
Pharmacokinetic Parameters ◽  
Control Group ◽  
Cytochrome P450 Enzyme ◽  
Sprague Dawley ◽  
Liver Cytochrome ◽  
Sd Rats

Abstract BackgroundThere is considerable evidence that many patients concurrently take dietary supplements with conventional drugs, with a risk of potential drug-supplement interaction. The aim of this study was to determine the effect of Cellgevity® supplement on selected rat liver cytochrome P450 (CYP) enzymes and on the pharmacokinetics of carbamazepine.MethodsSprague-Dawley (SD) rats were put into 5 groups and modulation of CYP enzyme activity by Cellgevity® was determined by comparing the enzyme activity of Cellgevity-treated groups with the negative control group after 30 days of treatment. For the effect of Cellgevity® on the pharmacokinetics of carbamazepine, 12 SD rats were put into 2 groups; one group received an oral administration of carbamazepine plus Cellgevity®, and the other carbamazepine plus normal saline. Blood samples were collected at specific time points and analyzed for levels of carbamazepine. ResultsActivities of CYP1A1/2, CYP2C9 and CYP2D6 were significantly increased by Cellgevity®. The pharmacokinetic parameters for rats administered carbamazepine with Cellgevity® vis-a-vis carbamazepine with normal saline were changed as follows: Cmax; 20 μmol/L vs 11 μmol/L, AUC0→24; 347 μmol.h/L vs 170 μmol.h/L, Ke; 0.28 h-1 vs 0.41 h-1, and t1/2; 2.3 h vs 1.7 h, respectively.ConclusionsCellgevity® increased the activity of rat CYP1A1/2, CYP2C9 and CYP2D6, and also altered the pharmacokinetics of carbamazepine in rats.

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