Pharma / Biotech

Identification of metabolites of novel Anti-MRSA fluoroquinolone WCK 771 in mice, rat, rabbit, dog, monkey and human urine using liquid chromatography tandem mass spectrometry.

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Identification of metabolites of novel Anti-MRSA fluoroquinolone WCK 771 in mice, rat, rabbit, dog, monkey and human urine using liquid chromatography tandem mass spectrometry.

Biomed Chromatogr. 2019 Mar 12;:e4532

Authors: Yeole RD, Rane VP, Ahirrao VK, Chavan RP, Patel AM, Deshpande PK, Patel MV, Patil KR

Abstract
WCK 771 is an L-arginine salt of Levonadifloxacin (LND) being developed as intra-venous dosage form and has recently completed Phase-III trial in India. The pharmacokinetics of WCK 771, a novel anti-MRSA fluoroquinolone, was examined in mice, rats, rabbits, dogs, monkeys and humans after systemic administration during pre-clinical and clinical investigations. Urine and serum were evaluated for identification of metabolites. It is observed that LND mainly follows phase-II biotransformation pathways. All the species showed different array of metabolites. In mice, rabbit and dog, the drug was mainly excreted in the form of O-glucuronide (M7) and acyl glucuronide (M8) conjugates. Whereas in rat and human major metabolite was sulfate conjugate (M6). Monkey exhibited equal distribution of sulfate (M6) and glucuronide conjugates (M7, M8). In addition to these three major phase-II metabolites; five phase-I oxidative metabolites (M1, M2, M3, M4 and M5) have been identified using liquid chromatography tandem mass spectrometry. Out of these eight metabolites M2, M3, M5, M7 and M8 have been reported first time.

PMID: 30861568 [PubMed – as supplied by publisher]

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