Generic - equivalent drugs use in internal and general medicine patients: distrust, confusion, lack of certainties or of knowledge? Part 3. Clinical issues

Abstract

The practical use of equivalent drugsIn the clinical practice, several aspects associated with the use of equivalent drugs need to be considered (Table 1). Determination of bioequivalence by means of studies in healthy volunteers as a single doseBioequivalence studies are performed on healthy volunteers. It is conventionally accepted that a similar bioavailability found in these people is a solid proof of a similar bioavailability in sick people! This model applied in vivo on healthy volunteers is considered adequate in most instances to detect formulation differences and to allow extrapolation of results to populations for which the reference medicinal product is approved (elderly, children, patients with renal or liver impairment, etc.). Another critical aspect of bioequivalence research is that it is recognized on the basis of studies carried out on a single dose, despite in clinical practice these drugs are administered in repeated doses to chronic patients. 1 In this respect, one might wonder whether single-dose studies on a limited number of healthy volunteers can adequately mirror the use of drugs in real life and whether the same results apply the most common groups of patients?. 2 According to some, in certain cases bioavailability tests need to be carried out on real patients. The question is not so much whether patients are different from volunteers, but rather whether, and when, these differences could cause two products that seem bioequivalent in normals become bioinequivalent in a clinical setting. A literature review aimed to study these factors in real patients has shown that only very few relevant publications are available on this topic. Moreover, involving patients instead of healthy volunteers would invariably increase inter-subject variability and possibly intra-subject variability as well. 3

Pharmacokinetic drug interaction between atorvastatin and ezetimibe in healthy Korean volunteers

“…[11,12] When co-administered with ezetimibe, the upper 90% CI of GMR for the C max,ss of atorvastatin slightly deviated from 1.25; however, this was not clinically significant considering that it is a highly variable drug. [13] Atorvastatin is generally metabolized by CYP3A4, and the resulting metabolite undergoes glucuronidation by uridine 5´-diphosphate-glucuronosyltransferase (UGT) 1A1 and 1A3. [6] Similarly, ezetimibe undergoes glucuronidation by UGT1A1, UGT1A3, and UGT2B15.…”

Generic medicine brand knowledge structure, relationships and purchase

“…Consequently, the affordability of high-quality generic medicines can lead to significant savings for patients (Dunne and Dunne, 2015; Dylst et al , 2013). The use of generic medicine has, therefore, been encouraged for socio-economic reasons (Nardi et al , 2014), especially in developing countries, where approximately 77% of the medicine expenditure is paid for with cash by patients, because they lack medical insurance (Hassali et al , 2009).…”

Pharmacokinetic Profile and Incurred Esomeprazole Sample Stability in Plasma Using High-Performance Liquid Chromatography - Photodiode Array

“…The issue of ESO stability should be a concern because it is sensitive to acidic pH, heat, and moisture and is also easily oxidized [7,9,10], all of which leads to poor long-term storage results on samples [7]. ESO is a highly variable drug (HVD), with coefficient of variation (CV)% of the pharmacokinetic parameters >30% [11]. The bioequivalence study regarding HVDs is schematically recommended using about 30 subjects to meet the requirements of the European Medicines Agency (EMA) and Food and Drug Administration [12].…”