Pharmacokinetics of Asacol 2.4 g/Day and Lialda 2.4 g/Day in Healthy Volunteers

This study evaluated pharmacokinetics of 5-ASA and N-Ac-5-ASA associated with each of 3 regimens of oral mesalamine 2.4 g/day (Lialda 2.4 g/day 2 x 1.2 g every 24 hours, Asacol® 6 x 400 mg every 24 hours, or Asacol 2 x 400 mg every 8 hours). Primary endpoints were 5-ASA area under the plasma concentration versus time curve from zero to 24 hours (AUC24) and total 5-ASA percent of dose excreted (A'e [%]) over the 24-hour period on Day 7.

• Drug: Asacol
  Asacol tablets, 6 tablets per day at 7 am for 7 days
• Drug: Asacol
  Asacol tablets, 400 mg, 2 tablets at 7 am, 3 pm, and 11 pm for 7 days
• Drug: Lialda
  Lialda tablets 1.2 g, 2 tablets once a day at 7 am for 7 days

• Experimental: 1
  Asacol 6x400 mg Q24h at 7 am for 7 days
  Intervention: Drug: Asacol
• Experimental: 2
  Asacol 2x400 mg Q8h at 7 am, 3 pm, and 11 pm for 7 days
  Intervention: Drug: Asacol
• Experimental: 3
  Lialda 2x1.2g Q24h at 7 am for 7 days
  Intervention: Drug: Lialda

Inclusion Criteria:

• Males or females between 18 and 45 years of age, inclusive, at screening and in good general health based on medical history, physical examination, and laboratory evaluation;
• If female, must be (as documented by patient reported medical history):
• postmenopausal (at least 1 year without spontaneous menses), or
• surgically sterile (tubal ligation or hysterectomy), or
• using acceptable contraception [e.g., sexual partner with non-reversed vasectomy (with azoospermia in 2 tests), 2 barrier methods (e.g., condom, diaphragm, or spermicide), or intra-uterine device];
• Body mass index (BMI) between 18 and 32 kg/m2, inclusive;
• Able to swallow the assigned study medication tablet whole; and,
• Able to fulfill the requirements of the protocol and provide written informed consent.

Exclusion Criteria:

• History or presence of any condition or gastrointestinal (GI) surgery causing malabsorption or an effect on GI motility;
• Any uncontrolled acute disease or major surgical operation requiring hospitalization within 1 month of screening;
• History of diabetes, syncope, cardiovascular, hepatic, or renal disease;
• Uncontrolled chronic diseases such as hypertension, systemic lupus erythematosus, or rheumatoid arthritis;
• History of cancer within the last 5 years (except for basal cell carcinoma with a documented 6-month remission);
• Any known enzyme-inducer, enzyme-inhibitor, or reported chronic exposure to enzyme-inducers such as paint solvents or pesticides within 30 days of treatment;
• Any prescription drug or herbal remedy within 14 days prior to scheduled dosing