Comparative Pharmacokinetic Study Among 3 Metformin Formulations in Healthy Mexican Volunteers: A Single-Dose, Randomized, Open-Label, 3-Period Crossover Study

Montoya-Eguía, Sandra Lucía; Garza-Ocañas, Lourdes; Badillo-Castañeda, Christian Tadeo; O, Eduardo Tamez-de la; Zanatta-Calderón, T.; Meza, Marco Vinicio Gómez; Garza-Ulloa, H.

doi:10.1016/j.curtheres.2014.09.003

Cited by 10 publications

(6 citation statements)

References 10 publications

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“…Even after adjusting for 6 comparisons, only 2.4% of the AUC T and AUC I 90% CIs and 21.4% of the C max 90% CIs failed to show BE. Our results are in line with some [ 17 , 22 ] but not all [ 15 , 16 ] published studies. Previous studies evaluated generic products on other national markets, examined only one [ 17 ] or two [ 16 , 22 ] generic products of a single drug, or were not performed in vivo [ 15 ].…”

Section: Discussionsupporting

confidence: 94%

“…Further, a similar analysis of US FDA-approved antiepileptic generic products found that AUC T and C max differed by >15% in 17% and 39% of simulated generic-generic switches, respectively [ 28 ]. Nevertheless, there is little direct empirical evidence regarding the extent of BE among reference-bioequivalent generic products; two amoxicillin generic products did not show BE [ 16 ], whereas two metformin generic products [ 22 ] and the two most disparate generic lamotrigine products [ 31 ] did.…”

Section: Discussionmentioning

confidence: 99%

“…Establishing surveillance systems of on-market generic products has been advocated [ 4 ] because of sporadic concerns about post-marketing quality [ 12 – 16 ]. Although several clinical studies [ 17 – 21 ] failed to detect important differences between reference and generic products, direct bioequivalence studies are limited [ 16 , 17 , 22 ].…”

Section: Introductionmentioning

confidence: 99%

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Generic-reference and generic-generic bioequivalence of forty-two, randomly-selected, on-market generic products of fourteen immediate-release oral drugs

Hammami

Padua

Hussein

et al. 2017

BMC Pharmacol Toxicol

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BackgroundThe extents of generic-reference and generic-generic average bioequivalence and intra-subject variation of on-market drug products have not been prospectively studied on a large scale.MethodsWe assessed bioequivalence of 42 generic products of 14 immediate-release oral drugs with the highest number of generic products on the Saudi market. We conducted 14 four-sequence, randomized, crossover studies on the reference and three randomly-selected generic products of amlodipine, amoxicillin, atenolol, cephalexin, ciprofloxacin, clarithromycin, diclofenac, ibuprofen, fluconazole, metformin, metronidazole, paracetamol, omeprazole, and ranitidine. Geometric mean ratios of maximum concentration (Cmax) and area-under-the-concentration-time-curve, to last measured concentration (AUCT), extrapolated to infinity (AUCI), or truncated to Cmax time of reference product (AUCReftmax) were calculated using non-compartmental method and their 90% confidence intervals (CI) were compared to the 80.00%–125.00% bioequivalence range. Percentages of individual ratios falling outside the ±25% range were also determined.ResultsMean (SD) age and body-mass-index of 700 healthy volunteers (28–80/study) were 32.2 (6.2) years and 24.4 (3.2) kg/m2, respectively. In 42 generic-reference comparisons, 100% of AUCT and AUCI CIs showed bioequivalence, 9.5% of Cmax CIs barely failed to show bioequivalence, and 66.7% of AUCReftmax CIs failed to show bioequivalence/showed bioinequivalence. Adjusting for 6 comparisons, 2.4% of AUCT and AUCI CIs and 21.4% of Cmax CIs failed to show bioequivalence. In 42 generic-generic comparisons, 2.4% of AUCT, AUCI, and Cmax CIs failed to show bioequivalence, and 66.7% of AUCReftmax CIs failed to show bioequivalence/showed bioinequivalence. Adjusting for 6 comparisons, 2.4% of AUCT and AUCI CIs and 14.3% of Cmax CIs failed to show bioequivalence. Average geometric mean ratio deviation from 100% was ≤3.2 and ≤5.4 percentage points for AUCI and Cmax, respectively, in both generic-reference and generic-generic comparisons. Individual generic/reference and generic/generic ratios, respectively, were within the ±25% range in >75% of individuals in 79% and 71% of the 14 drugs for AUCT and 36% and 29% for Cmax.ConclusionsOn-market generic drug products continue to be reference-bioequivalent and are bioequivalent to each other based on AUCT, AUCI, and Cmax but not AUCReftmax. Average deviation of geometric mean ratios and intra-subject variations are similar between reference-generic and generic-generic comparisons.Trial registration ClinicalTrials.gov identifier: NCT01344070 (registered April 3, 2011).Electronic supplementary materialThe online version of this article (doi:10.1186/s40360-017-0182-1) contains supplementary material, which is available to authorized users.

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Section: Discussionsupporting

confidence: 94%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Generic-reference and generic-generic bioequivalence of forty-two, randomly-selected, on-market generic products of fourteen immediate-release oral drugs

Hammami

Padua

Hussein

et al. 2017

BMC Pharmacol Toxicol

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“…Very similar C max (1163.5 ng/mL, 1184.6 ng/mL and 1167.8 ng/mL, reference and two generics, respectively) and AUC 0-t values (6240.7 ngÁh/mL, 6433.7 ngÁh/mL and 6567.1 ngÁh/mL, reference and two generics, respectively) were taken as an indication of bioequivalency of generics to the reference product by the authors (Montoya-Eguía et al, 2015) The plasma concentration profile of metformin after oral administration complies with the ''flip-flop'' type because the rate of absorption is slower than that of elimination (Bhavesh et al, 2007;Garrison et al, 2015).…”

Section: Pharmacokinetics Propertiesmentioning

confidence: 99%

Microparticulate and nanoparticulate drug delivery systems for metformin hydrochloride

Çetin

Şahin

2015

Drug Delivery

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Context: Metformin hydrochloride is a biguanide derivative widely used for the treatment of type 2 diabetes, prescribed nearly to 120 million people worldwide. Metformin has a relatively low oral bioavailability (about 50-60%). Although the major effect of metformin is to decrease hepatic glucose output as an antihyperglycemic agent, its inhibitory effects on the proliferation of some cancer cells (e.g. prostate, breast, glioma cells) have been demonstrated in the cell culture studies. Development of novel formulation (e.g. microparticles, nanoparticles) strategies for metformin might be useful to improve its bioavailability, to reduce the dosing frequency, to decrease gastrointestinal side effects and toxicity and to be helpful for effective use of metformin in cancer treatment. Objective: The main aim of this review is to summarize metformin HCl-loaded micro-and nanoparticulate drug delivery systems. Method: The literature was rewieved with regard to the physicochemical, pharmacological properties of metformin, and also its mechanism of action in type 2 diabetes and cancer. In addition, micro-and nanoparticulate drug delivery systems developed for metformin were gathered from the literature and the results were discussed. Conclusion: Metformin is an oral antihyperglycemic agent and also has potential antitumorigenic effects. The repeated applications of high doses of metformin (as immediate release formulations) are needed for an effective treatment due to its low oral bioavailability and short biological half-life. Drug delivery systems are very useful systems to overcome the difficulties associated with conventional dosage forms of metformin and also for its effective use in cancer treatment.

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“…It is mainly absorbed in the small intestine and 90% excreted unchanged in urine. 2,3 Sample preparation is one of the most vital parts in chemical analysis, especially for the determination of medical drugs in biological samples. Liquid-liquid extraction (LLE) method is most suitable for hydrophobic analytes as they will transfer easily to the organic phase unlike hydrophilic ones that will remain in the aqueous sample.…”

Section: Introductionmentioning

confidence: 99%

Preliminary Assays on Electrochemically Modulated Liquid-liquid Extraction of Metformin

Jajuli¹,

Hussin²,

Rahim³

et al. 2019

JPS

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Liquid-liquid extraction is one of the analytical methods that is commonly used for separation of various analytes. Nevertheless, the method is not capable to operate with hydrophobic medical drugs, particularly metformin where the drug is essentially used as an antidiabetic (Type II diabetes). Preliminary studies on extractions of metformin, phenyl biguanide and propranolol were accomplished using electrochemically modulated liquid-liquid extraction (EMLLE) method as a sample preparation method. The principle is based on application of electrically driving force to transfer the desired ions across the interface between two immiscible electrolyte solutions (ITIES). The extraction of three cationic drugs from artificial urine to 1, 2-dichoroethane, is controlled by external polarisation. By using ITIES cells, all of the drugs are found to transfer within the available potential window. The application of different galvani potential differences enables the selective extraction of drugs. Potential window of artificial urine shorter than lithium chloride as aqueous phase. Nevertheless, for both cases, the first drug to be extracted is propranolol which is the most hydrophobic drug and hence a lower potential is needed to transfer this cationic molecule across the interface as followed by phenylbiguanide and metformin.

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Comparative Pharmacokinetic Study Among 3 Metformin Formulations in Healthy Mexican Volunteers: A Single-Dose, Randomized, Open-Label, 3-Period Crossover Study

Cited by 10 publications

References 10 publications

Generic-reference and generic-generic bioequivalence of forty-two, randomly-selected, on-market generic products of fourteen immediate-release oral drugs

Generic-reference and generic-generic bioequivalence of forty-two, randomly-selected, on-market generic products of fourteen immediate-release oral drugs

Microparticulate and nanoparticulate drug delivery systems for metformin hydrochloride

Preliminary Assays on Electrochemically Modulated Liquid-liquid Extraction of Metformin

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