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Abstract

Novel Techniques in Nutrition and Food Science

Management of Idiopathic Nephrotic Syndrome: Co-Administration of Cyclosporine and Lyophilized Grapefruit Juice

Submission: February 28, 2018; Published: April 19, 2018

DOI: 10.31031/NTNF.2018.01.000522

ISSN 2640-9208
Volume1 Issue5

Abstract

Cyclosporine A (CsA) is effective in inducing or maintaining remission in patients with frequently relapsing or steroid-dependent nephrotic syndrome but unfortunately this remission is not long-lasting and most patients relapse within the few months following cessation of treatment. Use of drugs that slow CsA metabolism as ketoconazole was found to be successful in maintaining stable renal function. Certain limitations to the use of ketoconazole such as chronic liver disease, pregnancy and hypersensitivity have favored the potential use of a natural alternative. Grapefruit juice is an inhibitor of the intestinal cytochrome P-450 system, which is responsible for the first-phase metabolism of CsA. Standardized doses of grapefruit as lyophilized capsules (500mg/capsule) were administered concomitantly with CsA to study the changes in CsA pharmacokinetics. The percent rise of CsA exposure as measured by AUC was in the range of 10-25% and co-administration was found to be safe. To find which component is responsible for the observed in vivo interaction, five grapefruit juice components: Quercetin, Naringin, Naringenin, 6, 7-Dihydroxybergamottin (DHB) and Bergamottin (BEG) were screened as potential inhibitors of the metabolism of Saquinavir by human liver microsomes. Both DHB and BEG were found to be potent in vitro inhibitors of the CYP3A4-mediated metabolism of Saquinavir.

Abbreviations: DHB: Di Hydroxy Bergamot tin; BEG: Bergamot tin; CsA: Cyclosporine A; INS: Idiopathic Nephrotic Syndrome; GF: Grape Fruit

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