PHARMACOKINETIC INTERACTION BETWEEN LINEZOLID AND GRAPEFRUIT JUICE IN RATS

Grapefruit juice has been reported to increase the oral availability of many cytochrome P450 substrates, mainly by inhibiting the first-pass metabolism of the drugs metabolized by cytochrome P450 3A in the gut wall rather than in liver. Linezolid is the first of a new class of antimicrobial drugs, is indicated for the treatment of nosocomial pneumonia and complicated skin infections. It was developed a fast and simple liquid chromatography/ mass spectrometry/ mass spectrometry (LC/MS/MS) method able to quantify linezolid in rat plasma after oral administration. Finally, the developed and validated method was applied for the investigation of the pharmacokinetic interaction between linezolid and grapefruit juice. Rezumat Sucul de grapefruit poate determina cresterea biodisponibilităţii unor medicamente administratate pe cale orală in principal prin inhibarea activităţii citocromului P 450 (CYP), izoforma CYP 3 A 4 la nivel intestinal. Linezolidul face parte din clasa oxazolidinonelor - o nouă clasă de antibiotice utilizate in tratamentul pneumoniilor nosocomiale si a infecţiilor ţesuturilor moi. Lucrarea descrie o metodă LC/MS/MS simplă si rapidă de a cuantifica concentraţia linezolidului in plasma de sobolan alb Wistar, după administrare orală. Acestă metodă a fost validată si aplicată in studierea interacţiunii farmacocinetice intre linezolid si sucul de grapefruit.