{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T14:55:45Z","timestamp":1761058545806},"reference-count":15,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2006,3,10]],"date-time":"2006-03-10T00:00:00Z","timestamp":1141948800000},"content-version":"vor","delay-in-days":6522,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biopharm &amp; Drug Disp"],"published-print":{"date-parts":[[1988,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Steady\u2010state serum salicylic acid (SA) concentrations and the formation rates of salicyluric acid (SU), salicylphenolic glucuronide (SPG), salicylacyl glucuronide (SAG), and gentisic acid (GA), and the excretion rate of unchanged SA were determined in three normal subjects following the administration of a single oral dose of acetylsalicylic acid (ASA) 37 mg kg<jats:sup>\u22121<\/jats:sup> and during multiple dosing with ASA 56 mg kg<jats:sup>\u22121<\/jats:sup> day.<jats:sup>\u22121<\/jats:sup> Steady\u2010state SA concentrations fell 23 per cent during the 4\u2010week study period (mean \u00b1 SD: 239 \u00b1 35 to 183 \u00b1 23 \u03bcg ml<jats:sup>\u22121<\/jats:sup>;<jats:italic>p<\/jats:italic> &lt; 0.05). Absorption of drug did not decrease during this time. Significant increases in the <jats:italic>V<\/jats:italic><jats:sub>max<\/jats:sub> for SU and SPG formation occurred between baseline and during multiple dosing. Mean <jats:italic>V<\/jats:italic><jats:sub>max<\/jats:sub>SU increased from 0.93 to 1.68 mg kg<jats:sup>\u22121<\/jats:sup> h<jats:sup>\u22121<\/jats:sup> (<jats:italic>p<\/jats:italic> &lt; 0.05) and mean <jats:italic>V<\/jats:italic><jats:sub>max<\/jats:sub> SPG increased from 009 to 019 mg kg<jats:sup>\u22121<\/jats:sup>h<jats:sup>\u22121<\/jats:sup> (<jats:italic>p&lt;<\/jats:italic>005). First\u2010order rate constants for the formation of SAG and GA and for the excretion of unchanged SA did not change significantly between baseline and multiple dosing. The mechanism for the decline in Cp<jats:sub>ss<\/jats:sub>SA with time during high\u2010dose SA therapy is most likely due to the induction of the formation rates of the major metabolites of SA, namely SU and SPG.<\/jats:p>","DOI":"10.1002\/bod.2510090306","type":"journal-article","created":{"date-parts":[[2006,10,14]],"date-time":"2006-10-14T11:27:50Z","timestamp":1160825270000},"page":"273-283","source":"Crossref","is-referenced-by-count":9,"title":["Changes in salicylate serum concentration and metabolism during chronic dosing in normal volunteers"],"prefix":"10.1002","volume":"9","author":[{"given":"Richard O.","family":"Day","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel E.","family":"Furst","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sydney H.","family":"Dromgoole","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Harold E.","family":"Paulus","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2006,3,10]]},"reference":[{"key":"e_1_2_1_2_2","doi-asserted-by":"publisher","DOI":"10.1002\/jps.2600540703"},{"key":"e_1_2_1_3_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM197208312870903"},{"key":"e_1_2_1_4_2","doi-asserted-by":"publisher","DOI":"10.1002\/cpt1972132258"},{"key":"e_1_2_1_5_2","doi-asserted-by":"publisher","DOI":"10.1185\/03007997509113680"},{"key":"e_1_2_1_6_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2125.1980.tb04794.x"},{"key":"e_1_2_1_7_2","doi-asserted-by":"publisher","DOI":"10.2165\/00003088-198308030-00005"},{"key":"e_1_2_1_8_2","doi-asserted-by":"publisher","DOI":"10.3109\/03602537909046431"},{"key":"e_1_2_1_9_2","unstructured":"M. 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