Pharmacokinetics of aminophylline delivered to the small intestine and colon using remote controlled capsules

• Published in: Chinese medical journal 2010-02, Vol.123 (3), p.320-325
• Main Authors: Liu, Hong-ying, Pi, Xi-tian, Zheng, Xiao-lin, Hou, Wen-sheng, Cui, Jian-guo
• Format: Article
• Language: English
• Subjects: Adult; Aminophylline - administration & dosage; Aminophylline - pharmacokinetics; Capsules - administration & dosage; Capsules - pharmacokinetics; Colon - metabolism; Humans; Intestine, Small - metabolism; Male; Young Adult; 农村信用社; 小肠吸收; 氨茶碱; 混凝土技术; 碾压混凝土; 胃肠道; 药物吸收; 药物输送
• ISSN: 0366-6999; 2542-5641
• DOI: 10.3760/cma.j.issn.0366-6999.2010.03.012

Background A patented remote controlled capsule （RCC） has recently been developed to provide noninvasive drug delivery to selected sites in the human gut that allows assessment of regional gastrointestinal （GI） drug absorption under a normal physiological environment. The objective of this study was to investigate the rate and extent of aminophylline absorption after site-specific delivery of the drug in the GI tract using RCC and a magnetic marker monitoring （MMM） technique. Methods This study was conducted in twelve healthy male subjects, in a three-treatment, randomized, crossover manner with a 7-day washout. Eligible subjects received a 150 mg aminophylline dose through an oral administration, or via a remote controlled capsule, delivered to the small bowel or ascending colon. MMM was employed to monitor the GI transit of the RCC, and the radio-frequency signal was used to activate capsules at target sites. Blood samples were obtained at regular intervals until 24 hours post dose/activation. Plasma theophylline concentrations were measured by a TDx~ System Analyzer. A comparison of the PK profile with the oral dosing route of aminophylline was performed after delivery to the small bowel and colon. Results The RCC was well tolerated in volunteers. The mean capsule activation time for the small bowel and ascending colon was 2.07 hours and 6.08 hours post dose. Aminophylline had similar absorption profiles from the small bowel compared with the stomach, with an area under the curve （AUCt） ratio of 92% vs. the stomach, but a lower absorption profile from the ascending colon, with an AUCt ratio of 47.2% vs. the stomach. Conclusions The proprietary of the RCC and MMM technique offer the opportunity to obtain data on the intestinal absorption of a drug in humans under noninvasive conditions. Aminophylline is rapidly and efficiently absorbed from the small bowel. While colonic absorption was limited by the poor water condition although effective absorption was observed from the ascending colon. This provides an opportunity for rational development of modified-release formulations as well as alternative dosage forms.