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After a one-month washout period goats received theophylline at a daily IM dose of 2\u00a0mg\/kg b.wt. for seven consecutive days then tylosin was injected IM dose of 15\u00a0mg\/kg b.wt. two hours after the last theophylline dosing. Blood samples were collected before and at 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 10, 12, and 24\u00a0h post-injection. Samples were left to clot and then centrifuged to yield serum. Milk samples were collected before and at 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 48, and 72\u00a0h post-injection from each goat by hand milking. Tylosin serum concentrations were determined by high-performance liquid chromatography (HPLC). Tylosin concentrations versus time were analyzed by a noncompartmental method. Tylosin C\n                      <jats:sub>max<\/jats:sub>\n                      significantly declined from 1.73\u2009\u00b1\u20090.10 to 1.01\u2009\u00b1\u20090.11\u00a0\u00b5g\/ml, and attained T\n                      <jats:sub>max<\/jats:sub>\n                      values of 2 and 1\u00a0h, respectively in theophylline-pretreated goats. Moreover, theophylline pretreatment significantly shortened the elimination half-life (t\n                      <jats:sub>1\/2el<\/jats:sub>\n                      ) from 6.94 to 1.98\u00a0h, t\n                      <jats:sub>1\/2ka<\/jats:sub>\n                      from 0.62 to 0.36\u00a0h and the mean residence time (MRT) from 8.02 to 4.31\u00a0h, also Vz\/F and AUCs decreased from 11.91 to 7.70\u00a0L\/kg and from 12.64 to 4.57\u00a0\u00b5g*h\/ml, respectively, consequently, theophylline enhanced the clearance (Cl\/F) of tylosin from the body. Similarly, tylosin milk concentrations were significantly lower in theophylline-pretreated goats than in goats that received tylosin alone and were detected up to 24 and 72\u00a0h in both groups, respectively. Moreover, the t\n                      <jats:sub>1\/2el<\/jats:sub>\n                      and AUCs were significantly decreased from 14.68\u2009\u00b1\u20091.97 to 4.72\u2009\u00b1\u20090.48\u00a0h, and from 181 to 67.20\u00a0\u00b5g*h\/ml, respectively.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The withdrawal period for tylosin in goat milk is at least 72\u00a0h. Theophylline pretreatment significantly decreases serum and milk tylosin concentrations to subtherapeutic levels, which could have serious clinical consequences such as failure of therapy. This means that after administering tylosin to goats, milk from these animals should not be consumed for at least 96\u00a0h to ensure that the milk is free from residues of the antibiotic.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12917-024-04089-6","type":"journal-article","created":{"date-parts":[[2024,6,7]],"date-time":"2024-06-07T23:25:44Z","timestamp":1717802744000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Effect of theophylline on serum and milk pharmacokinetics of tylosin following intramuscular administration in lactating goats"],"prefix":"10.1186","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2214-0130","authenticated-orcid":false,"given":"Fatma Sayed","family":"EL-Tareef","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7636-7018","authenticated-orcid":false,"given":"Khaled","family":"Abo-EL-Sooud","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohamed","family":"Karmi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3299-4404","authenticated-orcid":false,"given":"Ahmed","family":"Hafez","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2024,6,8]]},"reference":[{"key":"4089_CR1","doi-asserted-by":"crossref","unstructured":"Ramsay RR, Popovic-Nikolic MR, Nikolic K, Uliassi E, Bolognesi ML. 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All procedures were followed in compliance with the applicable norms and legislation. The research was done in accordance with the ARRIVE criteria. An informed consent from the owner(s) to use the animals in our study was obtained.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"251"}}