Background/Objectives: Fixed-dose combinations (FDCs) improve therapeutic adherence in type 2 diabetes. These studies aimed to evaluate the pharmacokinetics and establish the bioequivalence of four immediate-release empagliflozin/metformin FDC formulations under fed conditions in healthy Mexican subjects. Methods: A total of 42 healthy volunteers per study (168 total) were enrolled in four randomized, open-label, two-way crossover, single-dose studies with a 14-day washout period. Formulations were administered orally under standardized fed conditions. Plasma concentrations of both drugs were quantified using a validated liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) method. Results: Across all dose strengths, the 90% confidence intervals (CIs) for the geometric mean ratios of peak plasma concentration (C_max) and area under the concentration–time curve (AUC_0-t) for both empagliflozin and metformin were entirely within the 80.00–125.00% bioequivalence acceptance range. The specific 90% CIs for C_max and AUC_0-t were: Study A (5/850 mg): empagliflozin (90.18–103.16%; 94.37–101.81%), metformin (98.43–107.69%; 97.18–106.62%); Study B (12.5/500 mg): empagliflozin (91.94–102.77%; 93.38–98.51%), metformin (92.58–101.73%; 94.85–103.91%); Study C (12.5/850 mg): empagliflozin (95.47–107.74%; 95.34–101.25%), metformin (94.19–103.59%; 94.06–103.21%); and Study D (12.5/1000 mg): empagliflozin (94.53–107.10%; 98.13–105.66%), metformin (98.89–107.51%; 99.25–109.92%). Regarding safety, no serious adverse events occurred, and all reported events were mild or moderate and resolved completely. Conclusions: All evaluated empagliflozin/metformin FDCs successfully demonstrated bioequivalence and a favorable safety profile under fed conditions. These findings fulfill regulatory requirements and support their therapeutic interchangeability in clinical practice. An exploratory power-model analysis indicated a modest trend toward less-than-dose-proportional metformin exposure across the 500–1000 mg range (slope β ≈ 0.77–0.78). NCT07633015, NCT07633054, NCT07633028, and NCT07633041.

Background/Objectives: Management of Type 2 Diabetes (T2D) frequently requires combination therapy. Fixed-dose combinations (FDCs) of sitagliptin and extended-release (ER) metformin improve therapeutic adherence but pose biopharmaceutical challenges related to matrix robustness and food–drug interactions. This study evaluated the pharmacokinetics and bioequivalence of two generic sitagliptin/metformin ER FDCs (50/1000 mg and 100/1000 mg) versus reference products under fasting and fed conditions in healthy Mexican subjects. Methods: Four independent, randomized, open-label, two-period, single-dose crossover studies were conducted. We enrolled 184 healthy subjects (46 per study) with a 7-day washout period. Plasma concentrations of sitagliptin and metformin were quantified using a validated LC-MS/MS method. Results: The 90% confidence intervals for the geometric mean ratios (Test/Reference) of C_max, AUC_0–t, and AUC_0-∞ for both analytes fell entirely within the 80.00–125.00% bioequivalence acceptance range across all studies. Under fed conditions, prolonged tmax and the absence of concentration spikes confirmed ER matrix preservation, with no evidence of food-induced dose dumping. The safety profile was highly favorable; all adverse events were mild or moderate and completely resolved without sequelae. Conclusions: The evaluated generic sitagliptin/metformin ER FDCs demonstrated pharmacokinetic bioequivalence to the reference products under fasting and fed conditions. These findings meet stringent regulatory requirements (NOM-177-SSA1-2013), support pharmacokinetic bioequivalence as the regulatory basis for safe therapeutic interchangeability, and provide robust, region-specific clinical data for the Latin American population. ClinicalTrials.gov identifiers: NCT07763899, NCT07763912, NCT07763951, and NCT07763964.

Background/Objectives: Major Depressive Disorder (MDD) is a complex psychiatric condition characterized by persistent low mood and cognitive dysfunction. Vortioxetine, a multimodal antidepressant, modulates serotonin receptor activity and inhibits the serotonin transporter. This study aimed to evaluate the bioequivalence and in vitro dissolution performance of a generic 20 mg vortioxetine formulation compared to the reference product under fasting conditions in healthy Mexican volunteers. Methods: This was a randomized, open-label, two-period, crossover study. Twenty healthy subjects were enrolled, and 18 completed both periods, with a 4-week washout period between them. Plasma concentrations were quantified using a validated LC-MS/MS method. Results: The 90% confidence intervals (CI) for the geometric mean ratios (Test/Reference) of C_max and AUC_0–72 were 92.32% [84.51–100.85] and 96.77% [91.10–102.80], respectively. Both parameters fell within the 80.00–125.00% bioequivalence acceptance range. No serious adverse events were reported. Conclusions: The generic vortioxetine formulation is bioequivalent to the reference product, supporting its therapeutic interchangeability for the treatment of MDD. NCT07624357.

Background/Objectives: Tamsulosin extended-release (ER) formulations minimize peak-related vasodilatory adverse events in benign prostatic hyperplasia (BPH) treatment. This study assessed the pharmacokinetics and bioequivalence of a generic tamsulosin 0.4 mg ER formulation against the innovator under fasting and fed conditions. Methods: Two randomized, open-label, four-period crossover, single-dose trials were conducted in healthy Mexican males. Subjects received treatment following a 10 h fast or a high-fat meal, with a 7-day washout. Plasma tamsulosin was quantified over 72 h via LC-MS/MS. An exploratory in vitro–in vivo correlation (IVIVC) analysis was also performed. Results: Analyses included 32 (fasting) and 58 (fed) subjects. In both states, 90% confidence intervals for C_max, AUC_0-t, and AUC_0-∞ geometric mean ratios fell entirely within the 80.00–125.00% bioequivalence limits. The formulations showed comparable dissolution (f₂ = 92.47), with numerical deconvolution proving most predictive in exploratory IVIVC. Notably, the pharmacokinetic profile of the test formulation was consistent with maintained controlled drug release under both dietary conditions and showed no pharmacokinetic evidence of food-induced dose dumping. Both formulations were well-tolerated; all adverse events were mild, with no clinically significant orthostatic hypotension observed. Conclusions: The generic tamsulosin 0.4 mg ER formulation is bioequivalent to the reference product in both fasting and fed states. Its structural robustness prevents dose dumping, ensuring a favorable hemodynamic safety profile. Comparable dissolution and IVIVC findings further support their reliability in vivo performance and therapeutic interchangeability. ClinicalTrials.gov identifiers: NCT07698288 and NCT07698275.

Background/Objectives: Type 2 diabetes is a group of metabolic disorders whose pathophysiological outcome is sustained hyperglycemia. Several medications are available for the treatment. SGLT2 simultaneously inhibits glucose and sodium reabsorption in the renal proximal tubule, resulting in urinary glucose excretion. This study assessed the pharmacokinetic profiles of two empagliflozin 25 mg drug products under fasting conditions in healthy Mexican subjects to establish bioequivalence. Methods: This was a randomized, open-label, two-way crossover, single-dose, prospective study with a 7-day washout period. Eligible subjects were healthy adult Mexican volunteers. The drugs were dosed orally, according to the randomization, after 10 h of fasting and 4 h before breakfast, with 250 mL of 10% glucose solution at room temperature. Serial blood samples were collected before and after dosing. Empagliflozin concentrations were analyzed using high-performance liquid chromatography–tandem mass spectrometry. Results: A total of 32 subjects were enrolled, and 30 completed the study. Pharmacokinetic parameters C_max, t_max, AUC_0–t, AUC _0–∞, and t_½ of empagliflozin for test and reference formulation, expressed as mean ± SD, were 578.28 ± 125.60 ng/mL, 2.72 ± 0.85 h, 4370.88 ± 769.50 ngh/mL, 4423.93 ± 776.02 ngh/mL, 7.62 ± 0.83 h, and 593.99 ± 156.78 ng/mL, 2.86 ± 1.00 h, 4313.24 ± 885.02 ngh/mL, 4368.04 ± 887.75 ngh/mL, and 7.61 ± 0.68 h, respectively. The 90% CI for C_max, AUC_0–t, and AUC _0–∞ were 98.30 [92.72–104.22], 101.72 [98.77–104.77], and 101.64 [98.73–104.63], respectively. Serious adverse events were not observed. Conclusions: Our study demonstrated bioequivalence between the empagliflozin formulations tested in healthy subjects under fasting conditions.