{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T23:27:30Z","timestamp":1776382050090,"version":"3.51.2"},"reference-count":20,"publisher":"Public Library of Science (PLoS)","issue":"1","license":[{"start":{"date-parts":[[2022,1,6]],"date-time":"2022-01-06T00:00:00Z","timestamp":1641427200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Epicur Pharma"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>Theophylline is an important drug for treatment of canine chronic bronchitis and bradyarrhythmias, but new products require validation since pharmacokinetics in dogs can vary by formulation. A new, 503B outsourcing facility-produced theophylline product (OFT) is available for veterinary use. Outsourcing facilities have many advantages over traditional compounding sources including current good manufacturing practice compliance. The purpose of this study was to establish the pharmacokinetics of OFT in dogs. Eight healthy dogs received 11 mg\/kg intravenous aminophylline and 10 mg\/kg oral OFT followed by serial blood sampling in a two-way, randomized, crossover design with 7-day washout. Plasma theophylline concentrations were quantified by liquid chromatography-mass spectrometry. Bioavailability, maximum concentration, time to maximum concentration, half-life and area under the curve were: 97 \u00b1 10%, 7.13 \u00b1 0.71 \u03bcg\/mL, 10.50 \u00b1 2.07 h, 9.20 \u00b1 2.87 h, and 141 \u00b1 37.6 \u03bcg*h\/mL, respectively. Steady-state predictions supported twice daily dosing of the OFT, but specific dosage recommendations are hindered by lack of a canine-specific therapeutic range for plasma theophylline concentration. These findings suggest that the OFT is well absorbed and can likely be dosed twice daily in dogs, but future pharmacodynamic and clinical studies are needed to establish a definitive therapeutic range for theophylline in this species.<\/jats:p>","DOI":"10.1371\/journal.pone.0262336","type":"journal-article","created":{"date-parts":[[2022,1,6]],"date-time":"2022-01-06T18:28:31Z","timestamp":1641493711000},"page":"e0262336","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":2,"title":["Pharmacokinetics of a 503B outsourcing facility-produced theophylline in dogs"],"prefix":"10.1371","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3021-5075","authenticated-orcid":true,"given":"Jennifer M.","family":"Reinhart","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gabriela A. R.","family":"de Oliveira","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lauren","family":"Forsythe","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhong","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2022,1,6]]},"reference":[{"key":"pone.0262336.ref001","first-page":"622","volume-title":"Current Veterinary Therapy","author":"EC Hawkins","year":"2014","edition":"15"},{"key":"pone.0262336.ref002","volume-title":"Textbook of Canine and Feline Cardiology: Principles and Clinical Practice","author":"PR Fox","year":"1999","edition":"2"},{"key":"pone.0262336.ref003","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1006\/phrs.1998.0394","article-title":"Comparative bioavailability of two sustained\u2010release theophylline formulations in the dog","volume":"38","author":"G Mengozzi","year":"1998","journal-title":"Pharmacol Res"},{"key":"pone.0262336.ref004","doi-asserted-by":"crossref","first-page":"1113","DOI":"10.2460\/javma.2004.224.1113","article-title":"Evaluation of the bioavailability and pharmacokinetics of two extended\u2010release theophylline formulations in dogs","volume":"224","author":"JE Bach","year":"2004","journal-title":"J Am Vet Med Assoc"},{"key":"pone.0262336.ref005","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1111\/j.1365-2885.1981.tb00718.x","article-title":"Pharmacokinetic studies of theophylline in dogs","volume":"4","author":"BC McKiernan","year":"1981","journal-title":"J Vet Pharmacol Ther"},{"key":"pone.0262336.ref006","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1111\/j.1365-2885.1986.tb00044.x","article-title":"Bioavailability of four slow\u2010release theophylline formulations in the beagle dog","volume":"9","author":"GD Koritz","year":"1986","journal-title":"J Vet Pharmacol Ther"},{"key":"pone.0262336.ref007","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1111\/jvp.12813","article-title":"Pharmacokinetics of a modified, compounded theophylline product in dogs","volume":"42","author":"CL Cavett","year":"2019","journal-title":"J Vet Pharmacol Ther"},{"key":"pone.0262336.ref008","unstructured":"Food, Drug, and Cosmetics Act of 1938, 21 U.S.C. 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