Computer-guided randomized concentration-controlled trials of tacrolimus in autoimmunity

Multiple sclerosis and primary biliary cirrhosis

J. McMichael, R. Lieberman, J. McCauley, W. Irish, I. Marino, Howard Doyle

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

A randomized concentration-controlled clinical trial (RCCCT) is a trial design in which patients are randomized to predefined blood drug concentrations (low, medium, high). If the concentration ranges are sufficiently separated, this study design can reveal important blood concentration-response relations. Tacrolimus is a potent yet 'infant' immunosuppressant for the treatment and prevention of graft rejection and has been shown to exhibit significant clinical activity in some immune-mediated disorders. A tacrolimus artificial intelligence modeling system (AIMS) was used to guide patient dosing to achieve target concentrations specified by the study protocols. In the Multiple Sclerosis study group, we were able to define a concentration range (0.3-0.7 ng/ml) that appeared to show efficacy and minimal tacrolimus toxicity. Patients randomized to the high zone (0.6-1.2 ng/ml) in the Primary Biliary Cirrhosis study group showed significant reduction (~50%) in surrogate efficacy markers [aspartate aminotransferase (SGOT), alanine aminotransferase (SGPT)] compared with patients in the low zone (0.1-0.6 ng/ml). Therefore the RCCCT allowed the detection and delineation of clinically significant concentration-response relations in an ethical and efficient manner.

Original languageEnglish (US)
Pages (from-to)435-437
Number of pages3
JournalTherapeutic Drug Monitoring
Volume18
Issue number4
DOIs
StatePublished - 1996
Externally publishedYes

Fingerprint

Biliary Liver Cirrhosis
Tacrolimus
Autoimmunity
Multiple Sclerosis
Randomized Controlled Trials
Aspartate Aminotransferases
Alanine Transaminase
Blood
Immunosuppressive Agents
Grafts
Artificial intelligence
Toxicity
Artificial Intelligence
Immune System Diseases
Graft Rejection
Biomarkers
Pharmaceutical Preparations
Therapeutics

Keywords

  • Autoimmunity
  • Concentration-response
  • Tacrolimus

ASJC Scopus subject areas

  • Toxicology
  • Health, Toxicology and Mutagenesis
  • Pharmacology
  • Biochemistry
  • Biochemistry, Genetics and Molecular Biology(all)
  • Pharmacology (medical)
  • Public Health, Environmental and Occupational Health

Cite this

Computer-guided randomized concentration-controlled trials of tacrolimus in autoimmunity : Multiple sclerosis and primary biliary cirrhosis. / McMichael, J.; Lieberman, R.; McCauley, J.; Irish, W.; Marino, I.; Doyle, Howard.

In: Therapeutic Drug Monitoring, Vol. 18, No. 4, 1996, p. 435-437.

Research output: Contribution to journalArticle

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