{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T08:26:04Z","timestamp":1786955164572,"version":"build-2736575974"},"reference-count":49,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T00:00:00Z","timestamp":1786665600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Asofarma de M\u00e9xico S.A. de C.V."}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>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\u2013in vivo correlation (IVIVC) analysis was also performed. Results: Analyses included 32 (fasting) and 58 (fed) subjects. In both states, 90% confidence intervals for Cmax, AUC0-t, and AUC0-\u221e geometric mean ratios fell entirely within the 80.00\u2013125.00% 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.<\/jats:p>","DOI":"10.3390\/pharmaceutics18081008","type":"journal-article","created":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T15:48:36Z","timestamp":1786722516000},"page":"1008","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Bioequivalence, Food-Effect Assessment and Exploratory IVIVC of Two Extended-Release Tamsulosin 0.4 mg Formulations in Healthy Mexican Subjects"],"prefix":"10.3390","volume":"18","author":[{"given":"Omar Emmanuel","family":"Hern\u00e1ndez Pi\u00f1a","sequence":"first","affiliation":[{"name":"Asofarma de M\u00e9xico S.A. de C.V., Av. Santa Fe 485, Lomas de Santa Fe, Contadero, Cuajimalpa de Morelos, Mexico City C.P. 05348, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7503-2328","authenticated-orcid":false,"given":"Alberto","family":"Mart\u00ednez Mu\u00f1oz","sequence":"additional","affiliation":[{"name":"Escuela Superior de Medicina, Instituto Polit\u00e9cnico Nacional, Salvador D\u00edaz Mir\u00f3n, Esq. Plan de San Luis S\/N, Casco de Santo Tom\u00e1s, Miguel Hidalgo, Mexico City C.P. 11340, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erika Gabriela","family":"Guido \u00c1vila","sequence":"additional","affiliation":[{"name":"Asofarma de M\u00e9xico S.A. de C.V., Av. Santa Fe 485, Lomas de Santa Fe, Contadero, Cuajimalpa de Morelos, Mexico City C.P. 05348, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4676-1625","authenticated-orcid":false,"given":"Abraham","family":"Escobedo-Moratilla","sequence":"additional","affiliation":[{"name":"Asofarma de M\u00e9xico S.A. de C.V., Av. Santa Fe 485, Lomas de Santa Fe, Contadero, Cuajimalpa de Morelos, Mexico City C.P. 05348, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Porfirio","family":"de la Cruz Cruz","sequence":"additional","affiliation":[{"name":"Doctorado Institucional en Ingenier\u00eda y Ciencia de Materiales (DICIM), Universidad Aut\u00f3noma de San Luis Potos\u00ed (UASLP), Av. Sierra Leona No. 550, Col. Lomas 2da. Secci\u00f3n, San Luis Potos\u00ed C.P. 78210, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0642-0033","authenticated-orcid":false,"given":"Jos\u00e9 Trinidad","family":"P\u00e9rez-Urizar","sequence":"additional","affiliation":[{"name":"Facultad de Ciencias Qu\u00edmicas, Universidad Aut\u00f3noma de San Luis Potos\u00ed, Av. Dr. Manuel Nava No. 6, Zona Universitaria, San Luis Potos\u00ed C.P. 78210, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1016\/j.eururo.2025.06.010","article-title":"Management of Non-neurogenic Male Lower Urinary Tract Symptoms: Better Holistic than Sequential","volume":"88","author":"Cornu","year":"2025","journal-title":"Eur. Urol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1016\/j.ucl.2016.04.001","article-title":"The Epidemiology of Benign Prostatic Hyperplasia Associated with Lower Urinary Tract Symptoms: Prevalence and Incident Rates","volume":"43","author":"Egan","year":"2016","journal-title":"Urol. Clin. N. Am."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"208","DOI":"10.4103\/0970-1591.127856","article-title":"Management of the complications of BPH\/BOO","volume":"30","author":"Speakman","year":"2014","journal-title":"Indian J. Urol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"36726","DOI":"10.1038\/s41598-025-20739-7","article-title":"Real-world safety assessment of tamsulosin based on adverse event analysis from the FAERS database","volume":"15","author":"Zhang","year":"2025","journal-title":"Sci. Rep."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"135","DOI":"10.2165\/00002512-200219020-00004","article-title":"Tamsulosin: A review of its pharmacology and therapeutic efficacy in the management of lower urinary tract symptoms","volume":"19","author":"Dunn","year":"2002","journal-title":"Drugs Aging"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1016\/j.urology.2021.01.022","article-title":"An Exploratory Analysis of Tamsulosin for Overactive Bladder (OAB) in Men With Varying Voiding Symptom Burden","volume":"153","author":"Johnson","year":"2021","journal-title":"Urology"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"11","DOI":"10.2147\/TCRM.S86","article-title":"Tamsulosin oral controlled absorption system (OCAS) in the treatment of benign prostatic hypertrophy","volume":"4","author":"Neill","year":"2008","journal-title":"Ther. Clin. Risk Manag."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"468","DOI":"10.1590\/S1677-55382011000400005","article-title":"The efficacy and safety of oral Tamsulosin controlled absorption system (OCAS) for the treatment of lower urinary tract symptoms due to bladder outlet obstruction associated with benign prostatic hyperplasia: An open-label preliminary study","volume":"37","author":"Lojanapiwat","year":"2011","journal-title":"Int. Braz. J. Urol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1156","DOI":"10.1021\/js960303k","article-title":"Disposition of the selective alpha1A-adrenoceptor antagonist tamsulosin in humans: Comparison with data from interspecies scaling","volume":"86","author":"Soeishi","year":"1997","journal-title":"J. Pharm. Sci."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"177","DOI":"10.2165\/11317580-000000000-00000","article-title":"Pharmacokinetics and pharmacodynamics of tamsulosin in its modified-release and oral controlled absorption system formulations","volume":"49","author":"Michel","year":"2010","journal-title":"Clin. Pharmacokinet."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"971","DOI":"10.1002\/cpdd.1589","article-title":"Pharmacokinetic Study and Bioequivalence Evaluation of Two Sustained-Release Tablets of Tamsulosin in Healthy Chinese Subjects Under Fasting and Postprandial Conditions","volume":"14","author":"Wang","year":"2025","journal-title":"Clin. Pharmacol. Drug Dev."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1038\/s41575-021-00539-w","article-title":"Foundations of gastrointestinal-based drug delivery and future developments","volume":"19","author":"Chu","year":"2022","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"100186","DOI":"10.1016\/j.nxnano.2025.100186","article-title":"An overview on developing the formulation to keep away the food impact on absorption","volume":"7","author":"Magar","year":"2025","journal-title":"Next Nanotechnol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.ejps.2019.04.003","article-title":"The mechanisms of pharmacokinetic food-drug interactions\u2014A perspective from the UNGAP group","volume":"134","author":"Koziolek","year":"2019","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1177\/147323000102900312","article-title":"Review of orthostatic tests on the safety of tamsulosin, a selective alpha1A-adrenergic receptor antagonist, shows lack of orthostatic hypotensive effects","volume":"29","author":"Yasukawa","year":"2001","journal-title":"J. Int. Med. Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1208\/s12248-023-00804-7","article-title":"Predicting Food Effects on Oral Extended-Release Drug Products: A Retrospective Evaluation","volume":"25","author":"Zou","year":"2023","journal-title":"AAPS J."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1089\/omi.2018.0114","article-title":"Interethnic Variability in CYP2D6, CYP2C9, and CYP2C19 Genes and Predicted Drug Metabolism Phenotypes Among 6060 Ibero- and Native Americans: RIBEF-CEIBA Consortium Report on Population Pharmacogenomics","volume":"22","author":"Naranjo","year":"2018","journal-title":"OMICS"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Villapalos-Garc\u00eda, G., Zubiaur, P., Navares-G\u00f3mez, M., Saiz-Rodr\u00edguez, M., Mej\u00eda-Abril, G., Mart\u00edn-V\u00edlchez, S., Rom\u00e1n, M., Ochoa, D., and Abad-Santos, F. (2021). Effects of Cytochrome P450 and Transporter Polymorphisms on the Bioavailability and Safety of Dutasteride and Tamsulosin. Front Pharmacol., 12.","DOI":"10.3389\/fphar.2021.718281"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Jessurun, N.T., Wijnen, P.A., Bast, A., van Puijenbroek, E.P., Bekers, O., and Drent, M. (2020). Tamsulosin Associated with Interstitial Lung Damage in CYP2D6 Variant Alleles Carriers. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21082770"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/j.prnil.2025.03.002","article-title":"Efficacy of tamsulosin 0.4 mg for the treatment in male with the international Prostate Symptom Score \u2265 20 compared with tamsulosin 0.2 mg","volume":"13","author":"Shin","year":"2025","journal-title":"Prostate Int."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"186","DOI":"10.4111\/icu.20250569","article-title":"The efficacy of tamsulosin 0.4 mg when tamsulosin 0.2 mg is insufficient for benign prostatic hyperplasia in Korean patients","volume":"67","author":"Chung","year":"2026","journal-title":"Investig. Clin. Urol."},{"key":"ref_22","first-page":"113","article-title":"Silodosin for the treatment of clinical benign prostatic hyperplasia: Safety, efficacy, and patient acceptability","volume":"6","author":"Cho","year":"2014","journal-title":"Res. Rep. Urol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"135","DOI":"10.2165\/00003495-200262010-00006","article-title":"Tamsulosin: An update of its role in the management of lower urinary tract symptoms","volume":"62","author":"Jarvis","year":"2002","journal-title":"Drugs"},{"key":"ref_24","first-page":"365","article-title":"Cardiovascular safety of tamsulosin modified release in the fasted and fed state in elderly healthy subjects","volume":"65","author":"Michel","year":"2004","journal-title":"Curr. Ther. Res. Clin. Exp."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1097\/JCP.0b013e318133fc23","article-title":"Dose dumping and the dumping of doses","volume":"27","author":"Shader","year":"2007","journal-title":"J. Clin. Psychopharmacol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2885","DOI":"10.1208\/s12249-018-1159-0","article-title":"Physiological Considerations and In Vitro Strategies for Evaluating the Influence of Food on Drug Release from Extended-Release Formulations","volume":"19","author":"Koziolek","year":"2018","journal-title":"AAPS PharmSciTech"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1016\/j.jconrel.2011.04.002","article-title":"Critical factors in the release of drugs from sustained release hydrophilic matrices","volume":"154","author":"Maderuelo","year":"2011","journal-title":"J. Control Release"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.eursup.2004.11.002","article-title":"The Pharmacokinetic Profile of Tamsulosin Oral Controlled Absorption System (OCAS\u00ae)","volume":"4","author":"Michel","year":"2005","journal-title":"Eur. Urol. Suppl."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.eursup.2005.07.003","article-title":"The improved cardiovascular safety of Omnic (tamsulosin) Oral Controlled Absorption System (OCAS\u00ae)","volume":"4","author":"Korstanje","year":"2005","journal-title":"Eur. Urol. Suppl."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1016\/j.ejpb.2014.02.008","article-title":"The design of controlled-release formulations resistant to alcohol-induced dose dumping\u2014A review","volume":"87","author":"Jedinger","year":"2014","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1093\/ajcn\/86.3.531","article-title":"Modulation by high-fat diets of gastrointestinal function and hormones associated with the regulation of energy intake: Implications for the pathophysiology of obesity","volume":"86","author":"Little","year":"2007","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1073","DOI":"10.1208\/s12249-012-9829-9","article-title":"Matrix tablets: The effect of hydroxypropyl methylcellulose\/anhydrous dibasic calcium phosphate ratio on the release rate of a water-soluble drug through the gastrointestinal tract I. In vitro tests","volume":"13","author":"Mamani","year":"2012","journal-title":"AAPS PharmSciTech"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Accennato, V.A.C., Costa, F., Riccio, M.F., Bernasconi, G., and Noboli, A.C. (2017). Bioequivalence Between Two Fixed Dose Combinations of Dutasteride and Tamsulosin in Male Subjects Under Fasting and Fed Conditions. Int. Ann. Med., 1.","DOI":"10.24087\/IAM.2017.1.10.346"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/j.addr.2016.05.007","article-title":"BDDCS, the Rule of 5 and drugability","volume":"101","author":"Benet","year":"2016","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"3167","DOI":"10.1021\/acs.molpharmaceut.5b00076","article-title":"Investigating the Discriminatory Power of BCS-Biowaiver in Vitro Methodology to Detect Bioavailability Differences between Immediate Release Products Containing a Class I Drug","volume":"12","author":"Pastoriza","year":"2015","journal-title":"Mol. Pharm."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1248\/cpb.59.529","article-title":"Formulation variation and in vitro-in vivo correlation for a rapidly swellable three-layered tablet of tamsulosin HCl","volume":"59","author":"Park","year":"2011","journal-title":"Chem. Pharm. Bull."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1159","DOI":"10.1016\/0031-9384(95)02061-6","article-title":"Fat increases vection-induced nausea independent of changes in gastric emptying","volume":"58","author":"Feinle","year":"1995","journal-title":"Physiol. Behav."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Abdullaev Sh, P., Shatokhin, M.N., Tuchkova, S.N., Abdullaev Sh, P., Teodorovich, O.V., Loran, O.B., and Sychev, D.A. (2023). Study of Allelic Variants of the CYP2D6 and CYP3A Genes on the Effectiveness and Safety of Tamsulosin Therapy in Patients with BPH: Results of a Pilot Study. Urologiia, 5\u201313. (In Russian).","DOI":"10.18565\/urology.2023.6.5-13"},{"key":"ref_39","first-page":"e38794","article-title":"A Review on Clinical Pharmacokinetics of Tamsulosin in Patients with Benign Prostatic Hyperplasia","volume":"6","author":"Mazdak","year":"2017","journal-title":"Jundishapur J. Chronic Dis. Care"},{"key":"ref_40","unstructured":"Ag\u00eancia Nacional de Vigil\u00e2ncia Sanit\u00e1ria (BR) (2026, June 19). Lista de Medicamentos de Refer\u00eancia-Lista A, Available online: https:\/\/www.gov.br\/anvisa\/pt-br\/setorregulado\/regularizacao\/medicamentos\/medicamentos-de-referencia\/arquivos\/lista-a-incluidos-05022025.pdf."},{"key":"ref_41","unstructured":"(2013). Que Establece las Pruebas y Procedimientos para Demostrar que un Medicamento es Intercambiable. Requisitos a que Deben Sujetarse los Terceros Autorizados que Realicen las Pruebas de Intercambiabilidad. Requisitos para Realizar los Estudios de Biocomparabilidad. Requisitos a que Deben Sujetarse los Terceros Autorizados, Centros de Investigaci\u00f3n o Instituciones Hospitalarias que Realicen las Pruebas de Biocomparabilidad (Standard No. NOM-177-SSA1-2013)."},{"key":"ref_42","unstructured":"World Medical Association (2024). WMA Declaration of Helsinki\u2013Ethical Principles for Medical Research Involving Human Subjects, World Medical Association. Available online: https:\/\/www.wma.net\/policies-post\/wma-declaration-of-helsinki-ethical-principles-for-medical-research-involving-human-subjects\/."},{"key":"ref_43","unstructured":"International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) (2023). ICH Harmonised Guideline: Good Clinical Practice (GCP) E6(R3), ICH. Available online: https:\/\/database.ich.org\/sites\/default\/files\/ICH_E6%28R3%29_DraftGuideline_2023_0519.pdf."},{"key":"ref_44","unstructured":"R Core Team (2021). R: A Language and Environment for Statistical Computing, R Foundation for Statistical Computing. Available online: http:\/\/www.r-project.org\/."},{"key":"ref_45","unstructured":"Chow, S.-C., and Liu, J.-P. (2009). Design and Analysis of Bioavailability and Bioequivalence Studies, Marcel Dekker, Inc.. [3rd ed.]."},{"key":"ref_46","unstructured":"U.S. Food and Drug Administration (2026, June 19). Bioanalytical Method Validation: Guidance for Industry, Available online: https:\/\/www.fda.gov\/files\/drugs\/published\/Bioanalytical-Method-Validation-Guidance-for-Industry.pdf."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"610","DOI":"10.1002\/jps.2600520629","article-title":"Per cent absorbed time plots derived from blood level and\/or urinary excretion data","volume":"52","author":"Wagner","year":"1963","journal-title":"J. Pharm. Sci."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"918","DOI":"10.1002\/jps.2600570602","article-title":"New method for calculating the intrinsic absorption rate of drugs","volume":"57","author":"Loo","year":"1968","journal-title":"J. Pharm. Sci."},{"key":"ref_49","unstructured":"United States Food and Drug Administration, and Center for Drug Evaluation and Research (2026, June 19). Extended Release Oral Dosage Forms: Development, Evaluation, and Application of In Vitro\/In Vivo Correlations, Available online: https:\/\/www.fda.gov\/media\/70939\/download."}],"container-title":["Pharmaceutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4923\/18\/8\/1008\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T08:07:44Z","timestamp":1786954064000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4923\/18\/8\/1008"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,14]]},"references-count":49,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2026,8]]}},"alternative-id":["pharmaceutics18081008"],"URL":"https:\/\/doi.org\/10.3390\/pharmaceutics18081008","relation":{},"ISSN":["1999-4923"],"issn-type":[{"value":"1999-4923","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,14]]}}}