کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2567555 1128336 2009 7 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Effect of food and antacids on the pharmacokinetics of pirfenidone in older healthy adults
موضوعات مرتبط
علوم پزشکی و سلامت پزشکی و دندانپزشکی پزشکی ریوی و تنفسی
پیش نمایش صفحه اول مقاله
Effect of food and antacids on the pharmacokinetics of pirfenidone in older healthy adults
چکیده انگلیسی

Pirfenidone is a small, synthetic molecule under investigation for treatment of idiopathic pulmonary fibrosis. In an open-label, single-dose crossover study, the pharmacokinetics (PK) of pirfenidone were investigated with or without food and antacids in healthy adult volunteers. Concentrations of pirfenidone and its metabolites in plasma and urine were determined by liquid chromatography with tandem mass spectrometry, and candidate pharmacokinetic models were fit to plasma data using weighted, non-linear regression. The effect of food and antacids on pirfenidone exposure was evaluated by determining ‘equivalence’ using FDA guidelines. Adverse events were recorded by site personnel and classified by investigators on the basis of severity and relationship to study drug.Sixteen subjects yielded 64 pharmacokinetic profiles. The best fit was achieved using a five-compartment, linear model with an allowance for direct conversion to the primary metabolite (5-carboxy-pirfenidone). Coadministration with food decreased the rate and, to a lesser degree, the extent of pirfenidone absorption of absorption. Analysis of adverse events revealed a correlation between pirfenidone Cmax and the risk of gastrointestinal (GI) adverse events, suggesting that food may reduce the risk of certain adverse events associated with pirfenidone. Administration of pirfenidone with food has a modest effect on overall exposure but results in lower peak concentrations, which may improve tolerability.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Pulmonary Pharmacology & Therapeutics - Volume 22, Issue 4, August 2009, Pages 279–285
نویسندگان
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