Pharmacokinetic Studies of Tacrolimus in Transplant Patients

Exclusion Criteria

• •1. Evidence of any acute rejection
• •2. Subjects who require dialysis within 6 months prior to study entry
• •3. Recipients of multiple organ transplants
• •4. Subjects who have tested positive for HBsAG or HIV, or who are recipients of organ from donors who are known to be HBsAG or HIV positive. Virology screening at the time of transplant.
• •5. Hep C positive subjects with liver biopsy proven recurrent disease considered relevant by physician oversight.
• •6. Subjects with any severe medical condition requiring acute or chronic treatment that in the investigator's opinion would interfere with study participation
• •7. History of malignancy, treated or untreated, with the past 2 years with the exception of carcinoma in situ or excised basal cell carcinoma, or hepatocellular carcinoma prior to transplant.
• •8. GFR ≤ 35 ml/min measured as estimated using the MDRD4 formula
• •9. Subjects with aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin ≥ 3 X upper limit of normal (ULN) or other evidence of severe liver disease
• •10. Subjects with white blood cell (WBC) count ≤2,000/ mm3 or with thrombocytopenia (platelet count ≤ 75,000/ mm3), with an absolute neutrophil count of ≤ 1,500/ mm3 or hemoglobin \<8g/dL)
• •11. Subjects with clinically significant infections, requiring therapy, which, in the investigator's opinion, would interfere with the objectives of the study
• •12. Other mental or physical conditions which in the investigator's opinion, are considered clinically significant
• •13. Presence of intractable immunosuppressant complications or side effects resulting in dose adjustment of tacrolimus
• •14. Subjects who have been exposed to an investigational therapy within 30 days prior to enrollment or 5 half-lives of the investigational product, whichever is greater.
• •15. An anticipated change in the immunosuppressive regimen during subject participation other than that required by the protocol
• •16. Subject with severe GI disturbance or diarrhea which could interfere with tacrolimus absorption
• •17. Severe diabetic gastroparesis
• •18. Initiation of any medications that could interfere with tacrolimus blood levels, including OTC medications, herbal supplements, grapefruit or grapefruit juice.
• •19. Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive beta human chorionic gonadotrophin (BhCG) laboratory test (\> 5 mIU/mL)
• •20. Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are
• •1. women whose career, lifestyle, or sexual orientation precludes intercourse with a male partner; women whose partners have been sterilized by vasectomy or
• •2. using a highly effective method of birth control (i.e. one that results in a less than 1% per year failure rate when used consistently and correctly, such as implants, injectables, combined oral contraceptives, and some intrauterine devices (IUDs); periodic abstinence (e.g. calendar, ovulation, symptothermal, post-ovulation methods) is not acceptable.