Scheen Aj Clinical Pharmacokinetics Of Metformin

Atc Phama | Publications

warning: call_user_func_array() expects parameter 1 to be a valid callback, function 'ctools_menu_help' not found or invalid function name in /var/www/www.atc-pharma.be/drupal-6.38/includes/theme.inc on line 669. Professor Andr J. SCHEEN, Universityof Lige, Belgium Clinical PharmacologyUnit(ATC) CHU ofLige Scheen AJ. Pharmacokinetics of dipeptidylpeptidase-4 inhibitors. Diabetes Metab Obes, 2010, 12, 648-658. Scheen AJ. Drug interactions of clinical importance with antihyperglycaemic agents : an update. Drug Safety, 2005, 28, 601-631. Scheen AJ. Diabetes, obesity, and metabolic syndrome. In : Nutrient-drug interactions (Ed : Meckling KA), CRC Press Taylor & Francis, Boca Raton, FL, US, 2007, 1-30. Scheen AJ. Pharmacokinetic interactions with thiazolidinediones. Clin Pharmacokinet, 2007, 46, 1-12. Scheen AJ. Drug-drug and food-drug pharmacokinetic interactions with new insulinotropic agents repaglinide and nateglinide. Clin Pharmacokinet, 2007, 46, 93-108. Scheen AJ. Dipeptidylpeptidase-4 inhibitors (gliptins) : Focus on drug-drug interactions. Clin Pharmacokinet, 2010, 49, 573-588. Scheen AJ. Cytochrome P450-mediated cardiovascular drug interactions. Exp Opin Drug Metab Toxicol, 2011, Aug 2. [Epub ahead of print] Radermecker RP, Scheen AJ. Serum plant sterols and atherosclerosis : is there a place for statin-ezetimibe combination ? (Letter). J Am Coll Cardiol, 2006, 47, 1496-1497. Legrand D, Krzesisnki JM, Scheen AJ. Quelle place pour une double ou triple inhibition du systme rnine-angiotensine-aldostrone. Rev Med Suisse, 2008, 4, 1792-1797. Scheen AJ et al. Long-term glycaemic control with metformin-sulphonylurea-pioglitazone triple therapy in PROactive (PROactive 17). Diabetic Med, 2009, 26, 1033-1039. Scheen AJ et al. Long-term glycaemic effects of pioglitazone vers Continue reading >>

Preventing, Delaying, Or Masking Type 2 Diabetes With Metformin In The Diabetes Prevention Program?

Preventing, Delaying, or Masking Type 2 Diabetes With Metformin in the Diabetes Prevention Program? From the Division of Diabetes, Nutrition and Metabolic Disorders, Department of Medicine, CHU Sart Tilman, Lige, Belgium Address correspondence and reprint requests to Andr J. Scheen, Division of Diabetes, Nutrition and Metabolic Disorders, Department of Medicine, CHU Sart Tilman (B35), B-4000 Lige, Belgium. E-mail: andre.scheen{at}chu.ulg.ac.be Diabetes Care 2003 Sep; 26(9): 2701-2701. The secondary analysis of the Diabetes Prevention Program (DPP) showed that withdrawal of metformin for 12 weeks resulted in a trend to a higher conversion rate from impaired glucose tolerance to diabetes as compared with the placebo group ( 1 ). This resulted in a reduction by 26% of the so-called prevention effect of metformin, i.e., from 31% in the primary analysis ( 2 ) to 25% in the secondary analysis, a reduction in the incidence of diabetes that, however, remained highly significant as compared with placebo. The same trend was observed in the Study to Prevent (STOP)- NIDDM trial with acarbose after a longer washout period of 3 months ( 3 ). As previously discussed ( 4 ) and emphasized in a previous Diabetes Care Editorial ( 5 ), one key question is to know whether the positive results with metformin in the DPP ( 2 ) or with acarbose in the STOP-NIDDM trial ( 3 ) could be interpreted as a real prevention of the disease or only as a delay in its progression, or even simply as a masking effect due to the metabolic effect of the drug. It was astonishing that a possible direct effect of metformin was not discussed in the original paper of the DPP, despite the fact that the results were initially presented without any washout period ( 2 ). Indeed, a significant improvement of insulin sen Continue reading >>

Protective Effect Of Metformin Against Walker 256 Tumor Growth Is Not Dependent On Metabolism Improvement

Protective Effect of Metformin Against Walker 256 Tumor Growth is Not Dependent on Metabolism Improvement Franco C.C.S.a Miranda R.A.a de Oliveira J.C.a Barella L.F.a Agostinho A.R.a Prates K.V.a Malta A.a Trombini A.B.a Torrezan R.a Gravena C.a Tfolo L.P.a de Sant'Anna J.R.b de Castro Prado M.A.A.b de Souza C.O.c de Souza H.M.c Beraldi E.J.d Mathias P.C.F.a aLaboratory of Secretion Cell Biology, Department of Biotecnology, Genetics and Cell Biology, State University of Maring, Maring/PR, Brazil; bLaboratory of Mutagenesis & Genetics, Department of Cell Biology and Genetics, State University of Maring, Maring/PR, Brazil; cDepartment of Physiological Sciences, State University of Londrina, Londrina/PR, Brazil; dDepartment of Morphological Sciences, State University of Maring, Maring/PR, Brazil Department of Biotechnology, Genetics and Cell Biology; Laboratory of Secretion Cell Biology - Block H67, room 19, State University of Maring/UEM - Colombo Avenue 5970, I have read the Karger Terms and Conditions and agree. Background/Aims: The objective of the current work was to test the effect of metformin on the tumor growth in rats with metabolic syndrome. Methods: We obtained pre-diabetic hyperinsulinemic rats by neonatal treatment with monosodium L-glutamate (MSG), which were chronically treated every day, from weaning to 100 day old, with dose of metformin (250 mg/kg body weight). After the end of metformin treatment, the control and MSG rats, treated or untreated with metformin, were grafted with Walker 256 carcinoma cells. Tumor weight was evaluated 14 days after cancer cell inoculation. The blood insulin, glucose levels and glucose-induced insulin secretion were evaluated. Results: Chronic metformin treatment improved the glycemic homeostasis in pre-diabetic MSG-rats, g Continue reading >>

Bioavalaibility And Pharmacokinetic Comparison Of Two Formulations Of Metformin 850 Mg Tablets In Healthy Colombian Volunteers

Colomb. Med.vol.42no.1CaliJan./Mar.2011 Bioavalaibility and pharmacokinetic comparison of two formulations of metformin 850 mg tablets in healthy Colombian volunteers Gloria Holgun, Esp1, Fanny Cuesta, IQ2, Rosendo Archbold, MSc3, Margarita Restrepo, MSc4, Sergio Parra, MSc5, Lina Pea, Esp6, Blanca Montoya, Bact7, Juan Carlos Ros, MSc8, Victoria Eugenia Toro, QF9, Adriana Ruiz, PhD10 1. Full Professor, Department of Pharmacy, Faculty of Pharmaceutical Chemistry, Universidad de Antioquia, Medelln, Colombia. e-mail: [email protected] 2. Full Professor (ret), ad Honorem, Department of Pharmacology and Toxicology, Faculty of Medicine, Universidad de Antioquia. e-mail: [email protected] 3. Full Professor and Director of the Graduate Program, Faculty of Pharmaceutical Chemistry, Universidad de Antioquia, Medelln, Colombia. e-mail: [email protected] 4. Full Professor, Department of Pharmacy, Faculty of Pharmaceutical Chemistry, Universidad de Antioquia. Chief of the Research Center, Faculty of Odontology, Universidad de Antioquia, Medelln, Colombia. e-mail: [email protected] 5. Assistant Professor, Department of Pharmacology and Toxicology. Coordinator of the Masters Program from the Corporation of Basic Biomedical Sciences. Faculty of Medicine, Universidad de Antioquia, Medelln, Colombia. e-mail: [email protected] 6. Assistant Professor, Department of Pharmacology and Toxicology, Faculty of Medicine, Universidad de Antioquia. Coordinator of the Graduate Program in Clinical Toxicology, Universidad de Antioquia, Medelln, Colombia. e-mail: [email protected] 7. Bacteriologist, Laboratory of Toxicology, Department of Pharmacology and Toxicology, Faculty of Medicine, Universidad de Antioquia, Medelln, Colombia. e-m Continue reading >>

A. J. Scheen, Clinical Pharmacokinetics Of Metformin, Clin Pharmacokinet, Vol. 30, No. 5, 1996, Pp. 359-371. Doi10.2165/00003088-199630050-00003 - References - Scientific Research Publishing

JOURNAL NAME: Pharmacology & Pharmacy , Vol.3 No.3 , July 5, 2012 ABSTRACT: Traditional treatment of type 2 diabetes mellitus (T2DM) has focused on correcting hyperglycemia. However, T2DM is almost always accompanied by other conditions and risk factors that affect its morbidity and mortality. Obesity represents one of the main risk factors associated in the T2DM and a modest weight loss around 5% is linked with significant reduction in the blood glucose levels. The objective of this study was to compare the pharmacokinetic parameters between two formulations of metformin, alone or combined with orlistat, in healthy volunteers. A single-blinded, single dose, two-period, two-sequence, crossover, randomized and balanced study design with a 7-day washout period was performed in 26 Mexican volunteers. Plasma samples were collected over a 24-hour period after administration of 500 mg metformin alone or combined with 60 mg orlistat in each period. A validated high-performance liquid chromatography coupled with a ultraviolet detector was used to analyze metformin concentration in plasma. Bioequivalence between metformin alone and metformin combined with orlistat was determined when the ratio for the 90% confidence intervals (CI) of area under the curve (AUC24h) and maximum concentration (Cmax) of the two formulations were within 80% and 125%. In the current study, the mean standard deviation (SD) of Cmax, AUC24h and AUC of the formulation containing only metformin were 1.39 0.44 g/mL, 7.59 3.17 g h/mL and 8.48 4.13 g h/mL, respectively, while the mean SD of Cmax, AUC24h and AUC of the formulation containing metformin and orlistat were 1.38 0.48 g/mL, 7.80 2.83 g h/mL and 9.13 4.29 g h/mL, respectively. The parametric 90% CI for Cmax and AUC24h were 87.5-109.3 and 88.7-124.7, Continue reading >>

Revisiting The Mechanisms Of Metformin Action In The Liver - Em|consulte

Revisiting the mechanisms of metformin action in the liver Les mcanismes daction de la metformine dans le foie revisits aDpartement endocrinologie, mtabolisme et cancer, Inserm, U1016, Institut Cochin, 24, rue du Faubourg-Saint-Jacques, 75014 Paris, France cUniversit Paris Descartes, Sorbonne Paris cit, 75014 Paris, France Although considerable efforts have been made since the 1950s to better understand the action of metformin, the first line therapeutic for type 2 diabetes, its mechanisms of action has not been fully elucidated. The main antidiabetic effect of this drug is to decrease hepatic glucose production. A plausible molecular mechanism of action now emerges from recent breakthroughs that place metformin at the control of energy homeostasis. Metformin was shown to induce a mild and transient inhibition of the mitochondrial respiratory chain complex 1. The resulting decrease in hepatic energy state activates the AMP-activated protein kinase (AMPK), a cellular metabolic sensor, and provided a generally accepted mechanism for metformin action on hepatic gluconeogenic program. However, the role of AMPK activation in metformin action has recently been challenged by loss-of-function experiments. Recent evidence showed that metformin-induced inhibition of hepatic glucose output is mediated by reducing cellular energy charge rather than direct inhibition of gluconeogenic gene expression. Furthermore, recent data support a novel mechanism of action for metformin involving antagonism of glucagon signaling pathways by inducing the accumulation of AMP, which inhibits adenylate cyclase and reduced levels of cAMP. The full text of this article is available in PDF format. Malgr lutilisation depuis les annes 1950de la metformine, lantidiabtique le plus couramment utilis dans l Continue reading >>

Scheen Aj Clinical Pharmacokinetics Of Metformin

Scheen Aj Clinical Pharmacokinetics Of Metformin Scheen Aj Clinical Pharmacokinetics Of Metformin Clinical pharmacokinetics of metformin. - NCBI . Scheen AJ(1). Author information: (1)Department of Medicine, CHU Sart Tilman, Lige, Belgium. The biguanide metformin (dimethylbiguanide) is an oral antihyperglycaemic agent widely used in the management of non-insulin-dependent diabetes mellitus (NIDDM). Considerable nbsp; Clinical pharmacokinetics of metformin. - NCBI . Graham GG(1), Punt J, Arora M, Day RO, Doogue MP, Duong JK, Furlong TJ, Greenfield JR, Greenup LC, Kirkpatrick CM, Ray JE, Timmins P, Williams KM. Author information: (1)Department of nbsp; Clinical Pharmacokinetics of Metformin - Springer Link with therapeutic doses ranging from 0.5 to l.5g, suggesting the involvement of an active, saturable absorption process. Metformin is rapidly distributed follow- ing absorption and does not bind to plasma proteins. No metabolites or conjugates of metformin have been identified. The absence of liver metabolism clearly nbsp; Clinical Pharmacokinetics of Metformin Request PDF - ResearchGate Article Literature Review in Clinical Pharmacokinetics 30(5):359-71 June 1996 with 267 Reads Andr J. Scheen. Abstract. The biguanide metformin (dimethylbiguanide) is an oral antihyperglycaemic agent widely used in the management of non-insulin-dependent diabetes mellitus (NIDDM). References in Metformin hydrochloride in the treatment of type 2 , A.J. Clinical pharmacokinetics of metformin. Clin Pharmacokinet. 1996;30:359 371. Crossref; PubMed; Scopus (389). 45.Sambol, N.C., Brookes, L.G., Chiang, J. et al, Food intake and dosage level, but not tablet vs solution dosage form, affect the absorption of metformin HCl in man. Br J Clin Pharmacol. 1996 nbsp; Metformin: from mechanisms of act Continue reading >>

Metabolic Acidosis In A Patient With Metformin Overdose

We report a rare fatal case of acute metformin overdose in a 19-year-old woman. A 19-year-old woman presented to a district-level emergency centre (EC) 1 hour after an intentional 'unquantifiable' metformin overdose. Clinical examination at that time was unremarkable except for a respiratory rate (RR) of 28 breaths per minute (bpm). No specific toxidrome was identified. In the EC, 6 hours post metformin ingestion, she appeared restless and complained of severe abdominal pain for which ranitidine, hyoscine butylbromide and lorazepam were administered orally. The patient was observed overnight in the EC. Eighteen hours post ingestion her tachypnoea worsened to 40 bpm and she developed hypoglycaemia with a finger prick blood glucose reading of 1.8 mmol/L. Venous blood gas findings taken at room temperature at this time are shown in Table 1 . Calculation of the anion gap was not possible because lactate and chloride values were not readily available. Based on the patient history and biochemical findings, a diagnosis of metabolic acidosis secondary to acute metformin overdose was made. Infusions of 5% dextrose w/v and 0.5% sodium bicarbonate were initiated separately, and the patient was immediately transferred to a secondary level hospital. Ongoing hypoglycaemia and worsening tachypnoea, accompanied by a drop in Glascow Coma Scale (GCS) to 12/15, occurred en route and 50 ml of a 50% dextrose bolus was administered. The patient developed a prolonged QT interval which precipitated cardiac arrest, with a GCS of 4T/15 requiring full resuscitation including inotropes. Arterial blood gas findings on 30% oxygen at this time revealed a metabolic acidosis as shown in Table 2 . At that time her creatinine was 235 mmol/L and the calculated increased anion gap was 27.3. The patient wa Continue reading >>

Metformin Drug Profile - Medicine Bibliographies - In Harvard Style

Not logged in. Log in or create an account These are the sources and citations used to research Metformin Drug Profile. This bibliography was generated on Cite This For Me on Your Bibliography: Alchetron (2017). Galega officinalis. [image] Available at: [Accessed 23 Aug. 2017]. Your Bibliography: Metrovi, T. (2015). Metformin History. [online] News-Medical.net. Available at: [Accessed 23 Aug. 2017]. Your Bibliography: STRZINEK, W. (2014). Metformin Molecular Structure. [image] Available at: [Accessed 23 Aug. 2017]. Your Bibliography: Coomer, D. (2013). Chemistry. [Blog] The Best Chemistry Articles. Available at: [Accessed 23 Aug. 2017]. Your Bibliography: Bryant, B. and Knights, K. (2015). Pharmacology for health professionals. 4th ed. Chatswood, NSW: Elsevier, pp.771-772. Your Bibliography: Ministry of Health NZ. (2014). 1 July 2014 changes to prescribing. [online] Available at: [Accessed 24 Aug. 2017]. Your Bibliography: Scott, A. (2012). Is Metformin Effective for Weight Loss?. [online] Medscape. Available at: [Accessed 24 Aug. 2017]. Your Bibliography: Diabetes Forecast. (2010). The Origins of Metformin. [online] Available at: [Accessed 24 Aug. 2017]. Metformin - FDA prescribing information, side effects and uses Your Bibliography: Drugs.com. (2017). Metformin - FDA prescribing information, side effects and uses. [online] Available at: [Accessed 24 Aug. 2017]. In-text: (New Zealand Data Sheet - Metformin, 2017) Your Bibliography: New Zealand Data Sheet - Metformin. (2017). [ebook] New Zealand: Medsafe, pp.1-12. Available at: [Accessed 24 Aug. 2017]. In-text: (Metformin Generic Health, 2015) Your Bibliography: Metformin Generic Health. (2015). [ebook] New Zealand: Medsafe, pp.1-9. Available at: [Accessed 24 Aug. 2017]. Mechanism of Metformin: A Tale of Two Sites You Continue reading >>

Population Pharmacokinetics Of Metformin In Mexican Patients With Type 2 Diabetes Mellitus

Population Pharmacokinetics of Metformin in Mexican Patients with Type 2 Diabetes Mellitus The aim of this study was to develop a Population Pharmacokinetic Model (PPM) for Metformin and to determine the influence of physiologic covariates on its pharmacokinetic variability in patients with Type 2 Diabetes Mellitus (T2DM). Ninety-nine patients with T2DM were included in the study. The clinical and pharmacokinetic data of 81 patients were used to build the population model and validated in others 18 patients. All patients received Metformin at a dose of 500-850 mg every 8 h. Blood samples were obtained at 2, 4, 6 or 8 h after drug administration, levels of drug were assayed by high performance liquid chromatography. The PPM was built using a nonlinear mixed effect program. The PPM was fitted to an open one compartment model, Ka = 2.22 h1 (CV61.5%), CL/F = 26.4 L h1 (CV 50.2%) and V/F = 365 L (CV 34.1%). Creatinine clearance (CLcr) and Lean Body Weight (LBW) correlated significantly with CL/F and V/F, respectively. The inclusion of these covariates in the basic model improved significantly the prediction performance as evaluated by the log-likelihood function. The final model was: CL/F = 16.6exp (0.00546CLcr), V/F = 209exp (0.0112LBW), with CV of 47 and 31.2%, respectively. In the PPM of metformin in Mexican patients with T2DM here described, the covariates, LBW and CLcr had a significant influence on interindividual variability of V/F and CL/F. Model evaluation suggested that the PPM is robust and its parameters were estimated with good precision. The model may be useful for clinician to design a rational initial dosage regimen in this patient population. Received: April 30, 2015; Accepted: June 12, 2015; Published: July 14, 2015 The incidence of type 2 Diabetes Mellitu Continue reading >>

Non-insulin-dependent Diabetes Mellitus In The Elderly

Volume 11, Issue 2 , July 1997, Pages 389-406 Non-insulin-dependent diabetes mellitus in the elderly Author links open overlay panel MD, PhDA.J.Scheen(Associate Professor) Get rights and content The prevalence of non-insulin-dependent diabetes mellitus dramatically increases with age. Older diabetic subjects have an increased frequency of complications from diabetes compared with their younger counterparts and higher morbidity and mortality rates compared with age-matched non-diabetic controls. Elderly patients with diabetes are generally treated following the same approach as in younger patients: dietary therapy first, followed by oral hypoglycaemic agents and ultimately insulin. However, several specificities should be pointed out. Changes associated with ageing may affect the pharmacokinetics and pharmacodynamics of both sulphonylureas (increasing the risk of severe hypoglycaemia) and biguanides (increasing the risk of lactic acidosis). The best insulin regimen in old age is not known, but a twice-daily injection of a pre-mixed insulin preparation is usually recommended. Goals of therapy must be realistic and not cause disabling side-effects. The general practitioner plays a crucial role in the care of elderly diabetic patients, but access to a multidisciplinary specialized team may be necessary. Continue reading >>

Loss Of Multidrug And Toxin Extrusion 1 (mate1) Is Associated With Metformin-induced Lactic Acidosis

Received 2011 August 24; Revised 2011 December 5; Accepted 2012 January 5. Copyright 2012 The Authors. British Journal of Pharmacology 2012 The British Pharmacological Society This article has been cited by other articles in PMC. Lactic acidosis is a fatal adverse effect of metformin, but the risk factor remains unclear. Multidrug and toxin extrusion 1 (MATE1) is expressed in the luminal membrane of the kidney and liver. MATE1 was revealed to be responsible for the tubular and biliary secretion of metformin. Therefore, some MATE polymorphisms, that cause it to function abnormally, are hypothesized to induce lactic acidosis. The purpose of this study is to clarify the association between MATE dysfunction and metformin-induced lactic acidosis. Blood lactate, pH and bicarbonate ion (HCO3-) levels were evaluated during continuous administration of 3 mgmL1 metformin in drinking water using Mate1 knockout (/), heterozygous (+/) and wild-type (+/+) mice. To determine the tissue accumulation of metformin, mice were given 400 mgkg1 metformin orally. Furthermore, blood lactate data were obtained from diabetic patients given metformin. Seven days after metformin administration in drinking water, significantly higher blood lactate, lower pH and HCO3- levels were observed in Mate1/ mice, but not in Mate1+/ mice. The blood lactate levels were not affected in patients with the heterozygous MATE variant (MATE1-L125F, MATE1-G64D, MATE2-K-G211V). Sixty minutes after metformin administration (400 mgkg1, p.o.) the hepatic concentration of metformin was markedly higher in Mate1/ mice than in Mate1+/+ mice. MATE1 dysfunction caused a marked elevation in the metformin concentration in the liver and led to lactic acidosis, suggesting that the homozygous MATE1 variant could be one of the risk Continue reading >>

Scheen, A.j. (1996) Clinical Pharmacokinetics Of Metformin. Clinical Pharmacokinetics, 30, 359-371. Doi10.2165/00003088-199630050-00003 - References - Scientific Research Publishing

JOURNAL NAME: Journal of Diabetes Mellitus , Vol.2 No.2 , May 25, 2012 ABSTRACT: Despite the extensive clinical experience with the use of metformin worldwide, no formal dose-ranging study has been conducted because the current dosing strategy of metformin was determined empirically, rather than by an understanding of its dose-response relationship in patients with type 2 diabetes. The present study was designed to evaluate the correlation between serum metformin levels and glycemic control, insulin resistance and leptin levels in females newly diagnosed with type 2 diabetes. Sixty type 2 diabetic females were recruited for the study and were allocated into 3 groups; each receiving metformin 1000, 1500 and 2000 mg/day respectively for 3 months. Blood samples withdrawn from each patient at zero time and after 3 months is used to evaluate serum levels of HbA1c, glucose, leptin and insulin, in addition, the measurement of serum level of metformin in blood after 3 months by HPLC. The results demonstrated that all the treated groups with different doses of metformin showed significant improve in all parameters; the use of increased metformin doses was only correlated with plasma leptin levels in the highest dose. In conclusion, serum metformin levels are not good predictors for correlating improvement in clinical and biochemical parameters with increasing the dose in newly diagnosed non-insulin resistant females with type 2 diabetes. Continue reading >>

Norcal Open Access Publications

Anti-Diabetic Effects of Niclosamide Ethanolamine and Metformin in Hanlin Tao1, Jingjing Guo2, Amer Hassa Al-Asadi1, Shengkan Jin1* 1Department of Pharmacology, Rutgers University, Piscataway, New Jersey 08854, USA 2Department of Food Science, Rutgers University, New Brunswick, New Jersey 08901, USA *Correspondence author: Shengkan Jin, Department of Pharmacology, Rutgers University-Robert Wood Johnson Medical School, 675 Hoes Lane West, R549, Piscataway, NJ 08854, USA, Tel: +1 7322354329, Fax: +1 7322354073; E-mail: [email protected] Citation: Tao H, Guo J, Al-Asadi AH, Jin S (2017) Anti-Diabetic Effects of Niclosamide Ethanolamine and Metformin in Mouse Models. J Diabetes Endocrinol Metab Disord 2017: 1-8. Received Date: 11 November 2017; Accepted Date: 15 December 2017; Published Date: 30 December 2017 We compared the anti-diabetic effects of mitochondrial uncoupler Niclosamide Ethanolamine (NEN) and the first-line drug metformin, and examined potential combinatory effect or drug-drug interaction between the two compounds in mouse models. We treated the High-Fat Diet (HFD)-induced diabetic and the db/db mice with NEN (~200 mg/kg.day), metformin (~75 mg/kg.day), or the two compounds together through oral administration, and monitored the exposure of the two compounds and effect on improving diabetic conditions. At the dosages tested in the present study, the co-treatment leads to plasma and liver exposures of NEN and metformin that are similar to treatment with each drug alone. In both animal models, NEN alone is more effective than metformin alone in reducing blood glucose. The co-treatment is significantly better than metformin alone in lowering blood glucose. NEN treatment alone is effective in reducing hepatic lipid accumulation, while metformin treatment d Continue reading >>

Clinical Pharmacokinetics Of Metformin.

1. Clin Pharmacokinet. 1996 May;30(5):359-71. (1)Department of Medicine, CHU Sart Tilman, Lige, Belgium. The biguanide metformin (dimethylbiguanide) is an oral antihyperglycaemic agentwidely used in the management of non-insulin-dependent diabetes mellitus (NIDDM).Considerable renewal of interest in this drug has been observed in recent years. Metformin can be determined in biological fluids by various methods, mainly usinghigh performance liquid chromatography, which allows pharmacokinetic studies inhealthy volunteers and diabetic patients. Metformin disposition is apparentlyunaffected by the presence of diabetes and only slightly affected by the use ofdifferent oral formulations. Metformin has an absolute oral bioavailability of 40to 60%, and gastrointestinal absorption is apparently complete within 6 hours of ingestion. An inverse relationship was observed between the dose ingested and therelative absorption with therapeutic doses ranging from 0.5 to 1.5 g, suggesting the involvement of an active, saturable absorption process. Metformin is rapidly distributed following absorption and does not bind to plasma proteins. Nometabolites or conjugates of metformin have been identified. The absence of livermetabolism clearly differentiates the pharmacokinetics of metformin from that of other biguanides, such as phenformin. Metformin undergoes renal excretion and hasa mean plasma elimination half-life after oral administration of between 4.0 and 8.7 hours. This elimination is prolonged in patients with renal impairment andcorrelates with creatinine clearance. There are only scarce data on therelationship between plasma metformin concentrations and metabolic effects.Therapeutic levels may be 0.5 to 1.0 mg/L in the fasting state and 1 to 2 mg/Lafter a meal, but monitoring has Continue reading >>