Browsing by Author "Mohan Kumar Ramasamy"

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Clinical Pharmacokinetic Drug Interaction Potential of MenoAct851 in Adult, Female Healthy Volunteers
(Excerpta Medica Inc., 2021) Vijayakumar Thangavel Mahalingam; Ilango Kaliappan; Satish Kumar Rajappan Chandra; Melvin George; Mohan Kumar Ramasamy; Sarvesh Sabarathinam; Dubey Govind Prasad
Background: MenoAct851 (Varanasi BioResearch Pvt. Ltd., Varanasi, India) is a patented polyherbal formulation developed to manage menopause symptoms that can be taken along with other allopathic medicines. Objective: The present study aims to evaluate the drug interaction potential of MenoAct851 to inhibit cytochrome (CY) P450 in vitro in rats, and to measure its effects on simvastatin pharmacokinetic parameters in healthy human volunteers. Methods: CYP450-carbon monoxide assay of MenoAct851 was performed in rat liver microsomes to calculate the percentage inhibition. Fluorometric assays of CYP3A4 and CYP2D6 determined half maximal inhibitory concentration value. A double-blind, randomized, placebo-controlled drug interaction study of MenoAct851 was conducted in 24 healthy adult female volunteers aged 25 to 50 years. The selected volunteers were randomized to receive placebo or MenoAct851 500 mg BID PO for 14 days. On the 15th day, each group received 40 mg single-dose simvastatin. Blood samples were drawn at different intervals to measure simvastatin pharmacokinetic parameters. Results: The mean (SD) CYP450 concentration of the diluted microsome sample was calculated and found to be 0.405 (0.12) nmol/mg. The inhibitory potential of MenoAct851 (41.16% [1.24%]) was found to be less than ketoconazole. Half maximal inhibitory concentration values of MenoAct851 on CYP3A4 and CYP2D6 were 11.96 (1.04) µg/mL and 15.24 (0.58) µg/mL, respectively, but they were higher than respective positive controls. There was no statistically significant difference between MenoAct851 and placebo groups concerning the pharmacokinetic parameters such as Cmax, Tmax, t½, and mean residence time of simvastatin; however, AUC showed a significant difference (P < 0.05) between the groups. Conclusions: MenoAct851 produced weaker interaction potential with CYP3A4 and CYP2D6 substrates based on in vitro assays, but the findings of clinical pharmacokinetic analysis indicate that MenoAct851 increased the AUC of simvastatin and simvastatin hydroxy acid. Therefore, coadministration of MenoAct851 might lead to drug-herb interaction, thereby affecting the therapeutic effect of CYP3A4 substrates. (Curr Ther Res Clin Exp. 2020; 81:XXX–XXX) © 2020
Comparative pharmacokinetic interactions of Quercetin and Rutin in rats after oral administration of European patented formulation containing Hipphophae rhamnoides and Co-administration of Quercetin and Rutin
(Springer-Verlag France, 2015) Ananth Kumar Kammalla; Mohan Kumar Ramasamy; Jyothi Chintala; Govind Prasad Dubey; Aruna Agrawal; Ilango Kaliappan
Quercetin and Rutin are most common flavone constituents of some herb extracts such as Hippophae rhamnoides L. Inter and intra herb pharmacokinetics interactions of Quercetin and Rutin were investigated in the present study. Pharmacokinetic study was investigated in the two groups of rats (n = 6) for pharmacokinetic interactions between the Quercetin and Rutin (2.5 mg/kg) mixture treated alone with European patented polyherbal formulation containing equivalent weight of the above. The total plasma concentrations of Quercetin and Rutin were determined by liquid chromatography mass spectrometry (LC-MS). A method was developed and validated according to the ICH guidelines. The results of the present study shows that there are great differences in the pharmacokinetics of Quercetin and Rutin when they are administered together and from the polyherbal formulation which will be interacted by many other constituents. The bioavailability of Quercetin was lowered from the polyherbal formulation when compared with the co-administration, whereas the Rutin bioavailability has increased from the polyherbal formulation when compared with the co-administration. The maximum plasma concentration of Quercetin from coadministration and polyherbal formulation was 165.3 ± 31.9 and 90.8 ± 21.4 ng/mL, respectively, whereas in the case of Rutin it was 61.1 ± 29.3 and 121.7 ± 19.2 ng/mL. After polyherbal formulation administration to rats the AUC0-24, AUC0-∞ and AUMC0-∞ of both Quercetin and Rutin significantly increased when compared to co-administration. The above results proved that inter and intra herb pharmacokinetic interactions between Quercetin and Rutin. Possible interactions of the other constituents with hydrolyzing enzymes in the formulation enhances the oral bioavailability of Rutin. Accordingly besides the drug herb interactions, inter and intra herb interaction might be brought into view with the wide use of herbal remedies. Graphical Abstract: [Figure not available: see fulltext.] © 2014 Springer International Publishing Switzerland.
Comparative Pharmacokinetic Study of Mangiferin After Oral Administration of Pure Mangiferin and US Patented Polyherbal Formulation to Rats
(Springer New York LLC, 2015) Ananth Kumar Kammalla; Mohan Kumar Ramasamy; Jyothi Inampudi; Govind Prasad Dubey; Aruna Agrawal; Ilango Kaliappan
The US patented polyherbal formulation for the prevention and management of type II diabetes and its vascular complications was used for the present study. The xanthone glycoside mangiferin is one of the major effector constituents in the Salacia species with potential anti-diabetic activity. The pharmacokinetic differences of mangiferin following oral administration of pure mangiferin and polyherbal formulation containing Salacia species were studied with approximately the same dose 30 mg/kg mangiferin and its distribution among the major tissue in Wistar rats. Plasma samples were collected at different time points (15, 30, 60, 120, 180, 240, 360, 480, 600, 1,440, 2,160, and 2880 min) and subsequently analyzed using a validated simple and rapid LC-MS method. Plasma concentration versus time profiles were explored by non-compartmental analysis. Mangiferin plasma exposure was significantly increased when administered from formulation compared to the standard mangiferin. Mangiferin resided significantly longer in the body (last mean residence time (MRTlast)) when given in the form of the formulation (3.65 h). Cmax values of formulation (44.16 μg/mL) administration were elevated when compared to equivalent dose of the pure mangiferin (15.23 μg/mL). Tissue distribution study of mangiferin from polyherbal formulation was also studied. In conclusion, the exposure of mangiferin is enhanced after formulation and administration and could result in superior efficacy of polyherbal formulation when compared to an equivalent dose of mangiferin. The results indicate that the reason which delays the elimination of mangiferin and enhances its bioavailability might the interactions of the some other constituents present in the polyherbal formulation. Distribution study results indicate that mangiferin was extensively bound to the various tissues like the small intestine, heart, kidney, spleen, and liver except brain tissue. © 2014, American Association of Pharmaceutical Scientists.
Development and validation of a RP-HPLC method for the simultaneous determination of Mangiferin, Ellagic acid and Hydroxycitric acid in polyherbal formulation
(EManuscript Services, 2014) Ananth Kumar Kammalla; Mohan Kumar Ramasamy; Aruna Agarwal; G.P. Dubey; Kaliappan Ilango
The US patented polyherbal formulation for the prevention and management of Type II diabetes and its vascular complications was used for the present study. The formulation consists of roots of Salacia species, leaves of Lagestroemia parviflora and fruit rind of Garcinia indica. The use of reversed phase C18 HPLC column was used and eluted with isocratic mobile phase of acetonitrile and phosphoric acid buffer solution enabled the efficient separation of chemical markers within 20min. Validation of the method was performed in order to demonstrate its selectivity, accuracy, precision, repeatability and recovery. All calibration curve shows good linear correlation coefficients (r2>0.995) within tested ranges. Three markers in this polyherbal formulation were quantified were Mangiferin (1.53% w/w), Ellagic acid (0.9655 w/w), Hydroxycitric acid (5.3% w/w). Intra and inter day RSDs of retention times and peak areas were less than 3%. The recoveries were between 95% and 102.5%. In conclusion a method has been developed for the simultaneous quantification of three markers in this polyherbal formulation. The established RP-HPLC method was simple, precise and accurate and can be used for the quality control of the raw materials as well as formulations.
Emerging need of pharmacokinetics in Ayurvedic system of medicine
(2013) Ilango Kaliappan; Ananth Kumar Kammalla; Mohan Kumar Ramasamy; Aruna Agrawal; Govind Prasad Dubey
Ayurveda is the most ancient system of traditional medicine of the world has been practicing in India. It has been facing constant challenges like standardization and pharmacokinetic profile of biomarkers in the Ayurvedic formulations. Due to these challenges there will be a potential decrease in the global herbal market. Presently Indian herbal market is about US $1.1 billion whereas Chinese herbal market is about US $10 billion per annum. Thus there is an urgent need of standardization and pharmacokinetics of the Ayurvedic formulations in order to achieve the uphold position in the global market. Pharmacokinetics which deals with the absorption, distribution, metabolism and excretion of the biomarkers or the new drug entity is the one of the regulatory requirement for an investigational new drug approval. Bioactive guided pharmacokinetic approach method is needed for Ayurvedic system of medicine to determine the pharmacokinetics of relevant markers in the formulation having number of markers. Also non compartmental analysis method should be applied for the analysis of pharmacokinetics of biomarkers from Ayurvedic formulations for successful pharmacokinetic evaluation. In this review we have explored the importance of pharmacokinetics in Ayurvedic system of medicine and integrated approaches for the pharmacokinetics in Ayurvedic system of medicine.