Bioequivalence testing of a new tablet formulation of generic fluoxetine

Abstract

The pharmacokinetics and relative bioavailability of fluoxetine capsules (reference) and tablets (test) were compared in 24 healthy subjects of both sexes after a single 20 mg oral dose of fluoxetine (as a hydrochloride salt). A randomized, crossover design with a 2-week wash-out period between each dose was applied. Serum samples, obtained before dosing and at various appropriate time points up to 192 hours, were analyzed for fluoxetine and norfluoxetine content by a simple, accurate and precise HPLC method. ANOVA, power analysis, 90% confidence intervals (CI), and two one-sided tests were used for the statistical analysis of pharmacokinetic parameters. The tolerability of the preparations was good. The respective point estimates of the ratios of the geometric means of log-Cmax and log-AUC(0-infinity) of fluoxetine were 0.912 and 0.935 with 90% of 0.838-0.992 and 0.857-1.020. The corresponding point estimates of norfluoxetine were 0.952 (90% CI = 0.843-1.075) and 0.904 (90% CI = 0.807-1.013), respectively. Since both 90% CI for the AUC(0-infinity). and Cmax geometric mean ratios of fluoxetine and norfluoxetine were included in the 80% to 125% interval proposed by the FDA the test drug (fluoxetine tablets) was considered bioequivalent to the reference one (Prozac capsules) according both to the rate and extent of absorption.

A review of the antimicrobial side of antidepressants and its putative implications on the gut microbiome

“…Appreciable amounts of SSRIs are predicted as being present. However, greater proportions of FLU, SER, PRX and FVX than ECIT and CIT are predicted as remaining (undissolved), which is consistent with these drugs taking less time to reach peak plasma concentration (De Vane et al, 2002; Hiemke and Härtter, 2000; Jovanović et al, 2006; Qamar and Safila, 2015).…”

“…(2) It should be noted that the PKs of SSRIs (De Vane et al, 2002;Hiemke and Härtter, 2000;Jovanović et al, 2006) and GI transit of medications (Adkin et al, 1993;Davis et al, 1986;Schiller et al, 2005) are highly variable. The actual variability of gut concentrations of SSRIs in the population will far exceed the ranges reported in Figure 1.…”

“…In the small intestine, the dissolution of SSRIs would be facilitated by bile salts (Mithani et al, 1996) and colonic dissolution of SSRIs would likely be facilitated by colonic mechanical forces, phospholipids, other fats and lectins (Shameem et al, 1995; Sutton, 2009). (2) It should be noted that the PKs of SSRIs (De Vane et al, 2002; Hiemke and Härtter, 2000; Jovanović et al, 2006) and GI transit of medications (Adkin et al, 1993; Davis et al, 1986; Schiller et al, 2005) are highly variable. The actual variability of gut concentrations of SSRIs in the population will far exceed the ranges reported in Figure 1.…”

Cost-effectiveness of improved primary care treatment of depression in women in Chile

“…There have been some reservations made about the use of generics but their effectiveness has been proven to be equivalent to patented formulations. 34 Nonetheless industry standards in low- and middle-income countries vary and quality control in the manufacture of these formulations is often unknown.…”

Evaluación de la maduración y calidad espermática epididimaria en ratas macho adultas expuestas a fluoxetina durante la gestación y lactancia

“…La FLX (N-methyl-3-phenyl-3-[4-(trifluoromethyl)phenoxy]propan-1-amino )(Figura 4) es un antidepresivo que pertenece al grupo de los ISRS, es uno de los fármacos más estudiados y cuenta con estudios clínicos en más de 45 países (Ferguson & Hill, 2006), debido a su potencial terapéutico es utilizado para el tratamiento de diversos trastornos psicopatológicos entre los cuales se encuentran incluidos los trastornos del ánimo, de alimentación y obsesivo-compulsivo entre otros (Jovanović et al, 2006).…”