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Analysis of LK-157 in plasma by LC-MS-MS: application to studies of pharmacokinetics and degradation pathways in rats and dogsIgličar, Petra, 1975- ...Multiple-species plasma-stability testing and pharmacokinetic studies in rats and dogs were performed on LK-157, a novel 10-ethylidene tricyclic carbapenem and potent inactivator of ?-lactamases of ... classes A, C, and D. An LC-MS-MS method was developed and validated for analysis of LK-157 in rat and dog plasma. Separation was achieved on a C18 column by gradient elution. The lowerlimit of quantification for LK-157 in plasma was 50 ng mL-1. Intra-day and inter-day precision were <12.5 and <11.8%, respectively. When degradation of LK-157 was assessed in buffer solutions and in rat, dog, and human plasma, the compound was found to be stable in pH 7.0-9.0 phosphate buffer for 24 h atroom temperature, and in human plasma for 60 min at 37 °C. The stability of LK-157 was species-dependent. Results from study of in vitro metabolism showed that the enzymes liver cytochrome P450 and uridine diphosphate glycosyltransferase do not metabolize LK-157. LC-MS-MS was also successfully applied to a pharmacokinetic study. The pharmacokinetics of LK-157 after bolus intravenous administration (10 mg kg-1) to Wistar rats and Beagle dogs was described by a two-compartment pharmacokinetic model. Human pharmacokinetic data were extrapolated from dog pharmacokinetic data. The extrapolated human terminal-phase half-life of LK-157 was 2.3 h. Stability and pharmacokinetic data for LK-157 are in agreement with results for other inactivators of ß-lactamases.Vir: Chromatographia. - ISSN 0009-5893 (Iss. 7-8, Vol. 70, 2009, str. 1103-1112)Vrsta gradiva - članek, sestavni delLeto - 2009Jezik - angleškiCOBISS.SI-ID - 2641777
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Baze podatkov, v katerih je revija indeksirana
Ime baze podatkov | Področje | Leto |
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Povezave do osebnih bibliografij avtorjev | Povezave do podatkov o raziskovalcih v sistemu SICRIS |
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Igličar, Petra, 1975- | 24898 |
Preželj, Andrej | 20246 |
Locatelli, Igor | 24399 |
Trontelj, Jurij | 23420 |
Andrenšek, Samo | 18671 |
Kovačič, Nataša, ekološke raziskave | ![]() |
Urleb, Uroš | 01878 |
Mrhar, Aleš | 06086 |
Vir: Osebne bibliografije
in: SICRIS
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