Study Of Pharmacokinetics and Pharmacodynamics Effects Of GSK256073A On Healthy Volunteers

Exclusion Criteria

• •Systolic blood pressure \< 100 mmHg or 150 mmHg and/or diastolic blood pressure = 100 mmHg at screening.
• •History of significant cardiac arrhythmias
• •Active peptic ulcer disease (PUD) and/or history of PUD within 1 year.
• •A serum uric acid concentration 8mg/dL
• •Screening test positive for H. Pylori using the non-radioactive breath test
• •History of gout and/or hyperuricemia
• •History of Gilbert's syndrome
• •A serum creatinine concentration above the normal reference range
• •History of kidney stones
• •PT and/or aPTT above the reference range
• •History of recurrent indigestion, stomach upset or diarrhea
• •Liver function tests (LFTs) or creatinine phosphokinase (CPK) 1.5X ULN
• •Screening stool test positive for occult blood
• •Screening peripheral blood smear with abnormal RBCs
• •CBC, MCV, and/or reticulocyte count corrected for haemoglobin level above the reference range at screening
• •Reduced G6PD activity
• •Serum haptoglobin outside the reference range at screening
• •Total serum LDH \> 1.25% above the ULN at screening
• •Positive HIV, Hepatitis B or Hepatitis C at screening
• •The subject has a positive pre-study urine drug/ serum alcohol screen.
• •History of alcohol consumption exceeding, on average, 7 drinks/week for women or 14 drinks/week for men within 6 months of the first dose of study medication or a positive alcohol test at screening
• •History of use of tobacco or nicotine containing products within 6 months of screening or a positive urine cotinine screen
• •Use of prescription (including hormone replacement therapy) or non-prescription drugs and vitamins within 7 days or 5 half-lives prior to administration of study medication. An exception is acetaminophen which is allowed at doses of 2g/day.
• •Use of dietary/herbal supplements within 14 days prior to treatment with study medication
• •Treatment with an investigational drug within 30 days or 5 half-lives (whichever is longer) prior to dosing.
• •Exposure to more than four new chemical entities within 12 months prior to the first dosing day.
• •History of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy that, in the opinion of the physician responsible, contraindicates their participation.
• •Where participation in study would result in donation of blood in excess of 500 mL within a 56 day period.
• •Unwillingness of male subjects to use a condom/spermicide
• •Pregnant or nursing women.
• •History of flushing (\>1 episode annually).
• •Fasting blood glucose 110 mg/dl and/or history of type I or type II DM
• •History of intra-ocular pathology
• •History of recurrent gum bleeding
• •History of bleeding haemorrhoids