Plenary Lecture

Calcineurin Inhibitor in Autoimmune Enteropathy Management

Dr. Hundie Tesfaye
Department of Medical Chemistry and Clinical Biochemistry
Division of Clinical Pharmacology
Faculty Hospital in Motol
2nd Faculty of Medicine
Charles University
Prague, Czech Republic

Abstract: Autoimmune enteropathy (AIE) is an entity reported primarily in infancy, resulting in intractable diarrhoea and associated with small bowel villous atrophy and the presence of circulating anti-enterocyte antibodies. It is a multisystem disorder with a response, in many cases, to immunosuppressive therapy. However, small bowel enteropathies that are associated with an autoimmune process are often resistant to initial treatment. Cyclosporine is a well known calcineurin inhibitor and potent immunosuppressive drug mostly used in organ transplantation. Since the mid-1980s, this drug is also being used to treat patients with inflammatory bowel diseases. At this time, cyclosporine is most useful in severely ill patients with ulcerative colitis, who have not responded to corticosteroid therapy. In such patients, intravenously administered cyclosporine may be highly effective for rapid disease control, thus changing a risky emergency situation into a less urgent procedure. However, cyclosporine is lipid-bound and may be associated with an increased risk of seizures when it is administered to acutely ill, severely malnourished patients with mal lipid absorption. The drug has a significant side effect profile that includes renal insufficiency and hypertension in some individuals. Therefore, therapeutic drug monitoring (TDM) is required for dosing of the drug to optimize immunosuppressive efficacy, while minimizing its side effects. Some data also indicate a correlation between trough concentrations and area under the curve (AUC), whereas others recommend 2 hours post dose (C2) drug concentration monitoring. The objective of the present paper is to demonstrate case model of effective outcomes of autoimmune entreopathy after therapeutic drug-monitoring guided calcineurin inhibitor, cyclosporine-A (CSA) therapy in a paediatric patient. The paper also discusses the new insights on mechanisms of action of calcineuin to control autoimmune diseases in general and autoimmune bowel diseases in particular.

Brief Biography of the Speaker: The author is MD, and PhD graduate of the Charles University, in Prague. Trained as Paediatrician and later as Clinical Pharmacologist, holds Board Certificate from the Institute for Postgraduate Education in Medicine. His present position is consultant in clinical pharmacology at the faculty hospital. The main interest and consultancy area of the author is in particular therapeutic drug monitoring in needy patients including, paediatric and geriatric populations given their pharmacokinetic/pharmacodynamic differences and vulnerability. The author participated in bioequivalence studies and clinical trials including as principal investigator and co-investigator. He is also dedicated to aid dosage adjustment for transplantation patients, oncology patients and others in intensive care including those with renal failure. The author participates in pregraduate and post graduate education both as a faculty member and as invited speaker in the field of clinical pharmacology dedicated for safe and better use of medicines for human wellbeing.