In Vivo Dissolution and Systemic Absorption of Immediate Release Ibuprofen in Human Gastrointestinal Tract under Fed and Fasted Conditions

• DOI: 10.1021/acs.molpharmaceut.7b00425
• Publication Date: 2017-09-22T14:07:23Z
• Authors: Mark J. Koenigskn...; Jason R. Baker; Bo Wen; Ann Frances; Huixia Zhang; Alex Yu; Ting Zhao; Yasuhiro Tsume; Manjunath P. Pai; Barry E. Bleske; Xinyuan Zhang; Robert Lionberger; Allen Lee; Gordon L. Amidon; William L. Hasler; Duxin Sun
• Keywords: Ibuprofen; Jejunum

In vivo drug dissolution in the gastrointestinal (GI) tract is largely unmeasured. The purpose of this clinical study was to evaluate and systemic absorption BCS class IIa ibuprofen under fed fasted conditions by direct sampling stomach small intestinal luminal content. Expanding current knowledge will help establish physiologically relevant vitro models predictive dissolution. A multilumen GI catheter orally inserted into healthy human subjects. Subjects received a single oral dose (800 mg tablet) with 250 mL water fasting conditions. facilitated collection fluid from stomach, duodenum, jejunum. Ibuprofen concentration supernatant plasma determined LC-MS/MS. total 23 subjects completed study, 11 returning for an additional visit (a 34 visits). were primarily white (61%) male (65%) average age 30 years. had median [min, max] weight 79 [52, 123] kg body mass index 25.7 [19.4, 37.7] kg/m2. levels higher remained detectable 28 h both AUC0-24 Cmax lower vs subjects, Tmax delayed detected immediately after ingestion until 7 dosing. Higher intestine soon dosing compared fed. contrast concentration, overall gastric concentrations due increased pH condition. near neutrality feedingbefore decreasing acidic h. Induction state reduced but ibuprofen, which suggest that slow emptying transit dominate effect concentration. finding high post unexpected. Future work needed better understand role various parameters, such as motility emptying, on order improve models.