Quinolone Antibiotics

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A R Rodriguez - One of the best experts on this subject based on the ideXlab platform.

Stefan Russmann - One of the best experts on this subject based on the ideXlab platform.

  • Drug safety of macrolide and Quinolone Antibiotics in a tertiary care hospital: administration of interacting co-medication and QT prolongation
    European Journal of Clinical Pharmacology, 2016
    Co-Authors: David Niedrig, Sarah Maechler, Liesa Hoppe, Natascia Corti, Helen Kovari, Stefan Russmann
    Abstract:

    Purpose Some macrolide and Quinolone Antibiotics (MQABs) are associated with QT prolongation and life-threatening torsade de pointes (TdP) arrhythmia. MQAB may also inhibit cytochrome P450 isoenzymes and thereby cause pharmacokinetic drug interactions (DDIs). There is limited data on the frequency and management of such risks in clinical practice. We aimed to quantify co-administration of MQAB with interacting drugs and associated adverse drug reactions. Methods We conducted an observational study within our pharmacoepidemiological database derived from electronic medical records of a tertiary care hospital. Among all users of MQAB associated with TdP, we determined the prevalence of additional QT-prolonging drugs and risk factors and identified contraindicated co-administrations of simvastatin, atorvastatin, or tizanidine. Electrocardiographic (ECG) monitoring and associated adverse events were validated in medical records. Results Among 3444 administered courses of clarithromycin, erythromycin, azithromycin, ciprofloxacin, levofloxacin, or moxifloxacin, there were 1332 (38.7 %) with concomitant use of additional QT-prolonging drugs. Among those, we identified seven cases of drug-related QT prolongation, but 49.1 % had no ECG monitoring. Of all MQAB users, 547 (15.9 %) had hypokalemia. Forty-four MQAB users had contraindicated co-administrations of simvastatin, atorvastatin, or tizanidine and three of those related adverse drug reactions. Conclusion In the studied real-life setting, we found a considerable number of MQAB users with additional risk factors for TdP but no ECG monitoring. However, adverse drug reactions were rarely found, and costs vs. benefits of ECG monitoring have to be weighted. In contrast, avoidable risk factors and selected contraindicated pharmacokinetic interactions are clear targets for implementation as automated alerts in electronic prescribing systems.

  • drug safety of macrolide and Quinolone Antibiotics in a tertiary care hospital administration of interacting co medication and qt prolongation
    European Journal of Clinical Pharmacology, 2016
    Co-Authors: David Niedrig, Sarah Maechler, Liesa Hoppe, Natascia Corti, Helen Kovari, Stefan Russmann
    Abstract:

    Purpose Some macrolide and Quinolone Antibiotics (MQABs) are associated with QT prolongation and life-threatening torsade de pointes (TdP) arrhythmia. MQAB may also inhibit cytochrome P450 isoenzymes and thereby cause pharmacokinetic drug interactions (DDIs). There is limited data on the frequency and management of such risks in clinical practice. We aimed to quantify co-administration of MQAB with interacting drugs and associated adverse drug reactions.

B Toussaint - One of the best experts on this subject based on the ideXlab platform.

Zhicong Yang - One of the best experts on this subject based on the ideXlab platform.

  • A pass-through solid-phase extraction clean-up method for the determination of 11 Quinolone Antibiotics in chicken meat and egg samples using ultra-performance liquid chromatography tandem mass spectrometry
    Microchemical Journal, 2019
    Co-Authors: Fenfang Deng, Lei Tan, Xiaoyan Luo, Xinhong Pan, Zhicong Yang
    Abstract:

    Abstract The major challenges in determination of antibiotic residues in foods stem from the complexity of matrix, as well as from polar differences and low concentrations of Antibiotics. In this study, an ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method has been developed for the determination of 11 Quinolone Antibiotics in chicken meat and egg samples using a pass-through solid phase extraction (SPE) cleanup procedure. The samples were treated with optimized acetonitrile/water solution to precipitate proteins, release and extract the target Antibiotics. Then, fats and phospholipids were removed by a pass-through SPE cleanup procedure. Subsequently, highly sensitive determination and confirmation of 11 Quinolones was accomplished by UPLC-MS/MS in the positive ionization mode with multiple reaction monitoring. Through the protocol, recoveries in chicken meat ranging from 70.4 to 98.4%, while in egg samples between 66.9 and 99.0%, with a low limit of detection ranged from 0.1 to 0.16 μg/kg. Finally, the method has been successfully utilized for the screening of eleven Quinolones Antibiotics residues in 60 chicken meat and 110 eggs samples from the local markets. Enrofloxacin and ciprofloxacin were detected in both chicken meat and eggs samples with the highest concentrations of 44.4 μg/kg and 6.22 μg/kg, respectively.

Yuichi Sugiyama - One of the best experts on this subject based on the ideXlab platform.

  • carrier mediated mechanism for the biliary excretion of the Quinolone antibiotic grepafloxacin and its glucuronide in rats
    Journal of Pharmacology and Experimental Therapeutics, 1998
    Co-Authors: Hiroyuki Sasabe, Akira Tsuji, Yuichi Sugiyama
    Abstract:

    Grepafloxacin (GPFX) has a comparatively greater hepatobiliary transport than other Quinolone Antibiotics. The biliary excretion mechanism of GPFX was investigated in a series of in vivo and in vitro studies with Sprague-Dawley rats and the mutant strain Eisai-hyperbilirubinemia rats (EHBR), which have a hereditary defect in their bile canalicular multispecific organic anion transport system (cMOAT). The biliary excretion of the parent drug in EHBR was 38% of that in normal rats, whereas the 3-glucuronide, a main metabolite of GPFX, was scarcely excreted into the bile in EHBR. To clarify the biliary excretion mechanism of GPFX, studies of uptake by bile canalicular membrane vesicle (CMV) were performed. ATP dependence was observed in the uptake of GPFX by CMV, although the extent was not very marked, whereas no ATP-dependent uptake was observed by CMV prepared from EHBR. An inhibition study of the ATP-dependent uptake of the glutathione conjugate, 2,4-dinitrophenyl-S-glutathione (DNP-SG), a typical substrate for cMOAT, was performed in order to differentiate among the affinities of six Quinolone Antibiotics for this transporter. All Quinolone Antibiotics inhibited the ATP-dependent uptake of DNP-SG with different half-inhibition concentrations (IC 50 ), and GPFX had the lowest IC 50 value. The uptake of GPFX-glucuronide by CMV from normal rats showed a marked ATP dependence, whereas there was little ATP-dependent uptake in EHBR. The K m value (7.2 μM) for the higher-affinity component of the glucuronide uptake was comparable to the K i value (9.2 μM) of the glucuronide in terms of inhibition of the ATP-dependent uptake of DNP-SG, which indicates that DNP-SG and the glucuronide may share the same transporter, cMOAT. The K i value of the glucuronide observed in this inhibition was less than 1/200 that of the parent, which suggests that the glucuronide had a much higher affinity than the parent drug. These results lead us to conclude that at least a part of the GPFX transport and a major part of its glucuronide transport across the bile canalicular membrane are by a primary active transport mechanism mediated by cMOAT.

  • kinetic evidence for active efflux transport across the blood brain barrier of Quinolone Antibiotics
    Journal of Pharmacology and Experimental Therapeutics, 1997
    Co-Authors: Tsuyoshi Ooie, Tetsuya Terasaki, Hiroshi Suzuki, Yuichi Sugiyama
    Abstract:

    A distributed model has been used to clarify the mechanism of the restricted and differential distribution of the Quinolone Antibiotics in the rat central nervous system (CNS). The symmetrical permeability clearances across the blood-brain barrier (BBB), PS BBB , and across the blood-cerebrospinal fluid barrier (BCSFB), PS CSF , and the active efflux clearances across the BBB, PS BBB,eff , were obtained from a nonlinear least squares regression analysis combined with the fast inverse Laplace transforming program for in vivo data. The values of PS BBB,eff were 10- to 260-fold greater than those of PS BBB , providing kinetic evidence to support the hypothesis that a significant efflux transport across the BBB is responsible for the limited distribution of Quinolones in brain tissue. Moreover, by simulation studies, we could demonstrate the concentration profiles in the brain as a function of the distance from the ependymal surface. However, active efflux transport across the BCSFB has been suggested to have only a slight effect on the apparent elimination from the cerebrospinal fluid. Comparing the apparent brain tissue-to-unbound serum concentration ratio at steady state, it has been suggested that the net flux across the BBB, i.e ., the ratio of PS BBB to the sum of PS BBB and PS BBB,eff , is a determinant for the differential distribution of these Quinolones in brain tissue. Such a putative active efflux transport system would play a significant role in decreasing the brain interstitial fluid concentration of Quinolones.

  • Carrier-mediated hepatic uptake of Quinolone Antibiotics in the rat.
    The Journal of pharmacology and experimental therapeutics, 1997
    Co-Authors: Hiroyuki Sasabe, Tetsuya Terasaki, Akira Tsuji, Yuichi Sugiyama
    Abstract:

    The systemic clearance of many Quinolone Antibiotics is mainly via metabolism and urinary excretion; by contrast, biliary excretion is a major route of elimination for a new Quinolone grepafloxacin (GPFX). Accordingly, we studied the hepatic uptake of GPFX because it is the first step in the drug’s hepatobiliary transport. The hepatic uptake of GPFX in vivo after i.v. administration was found to approach the hepatic blood flow, suggesting the existence of an effective hepatic uptake mechanism. To clarify this transport mechanism, GPFX uptake by isolated rat hepatocytes was examined and found to consist of a saturable component ( Km 173 μM, Vmax 6.96 nmol/min/mg) and a nonspecific diffusion component. The inhibition of GPFX uptake by ATP-depletors and a lack of effect after replacing Na+ with choline demonstrated that the uptake was an Na+-independent carrier-mediated active process. This uptake was inhibited by other Quinolones and for lomefloxacin this was competitive in nature. Mutual inhibition studies were undertaken to investigate whether the transporter for GPFX might be the same as other transporters so far identified. GPFX inhibited the uptake of taurocholic acid, pravastatin (organic anion), cimetidine (organic cation) and ouabain (neutral steroid). However, GPFX uptake was not inhibited by these compounds. Confirmation that GPFX uptake is blood flow limited was obtained by extrapolation of the in vitro data based on mathematical modeling. In conclusion, the effective hepatic uptake of Quinolone Antibiotics are via carrier-mediated active transport, which is distinct from that involved in the transport of bile acids, organic anions, organic cations or neutral steroids.

  • Comparative distribution of Quinolone Antibiotics in cerebrospinal fluid and brain in rats and dogs.
    The Journal of pharmacology and experimental therapeutics, 1996
    Co-Authors: Tsuyoshi Ooie, Tetsuya Terasaki, Hiroshi Suzuki, Yuichi Sugiyama
    Abstract:

    The distribution of the Quinolone Antibiotics, norfloxacin (NFLX), AM-1155, fleroxacin (FLRX), ofloxacin, sparfloxacin (SPFX) and pefloxacin (PFLX), in the central nervous system (CNS) was investigated in dogs and rats. In dogs, the steady-state cerebrospinal fluid (CSF) to unbound serum concentration ratio (Kp,uCSF) differed widely ranging from 0.11 (NFLX) to 1.0 (PFLX). About a 10-fold difference between compounds was also observed in the Kp,uCSF in rats; however, these values were 25 to 50% smaller than those in dogs. Similarly, the brain to unbound serum concentration ratio (Kp,uBrain) of Quinolones differed widely ranging from 0.15 (NFLX) to 1.5 (SPFX) in dogs and 0.04 (NFLX) to 0.33 (FLRX) in rats. The steady-state concentration ratio between CSF and brain tissue exhibited a 3-fold difference among Quinolones (0.5 for PFLX to 1.6 for SPFX) in dogs, whereas, these values were all close to unity in rats. Kp,uBrain and Kp,uCSF all increased as the lipophilicity of the compound increased (except the Kp,uBrain in dogs). We also found that the Quinolones inhibited the saturable accumulation of [14C]FLRX (Km 660 microM) by the isolated rat choroid plexus. About a 20-fold difference among the apparent IC50 values for FLRX transport was observed between NFLX (6000 microM) and PFLX (300 microM). The absence of a negative correlation between the affinity of the Quinolones for this transport system, which in turn represents the efflux clearance from the CSF, and their in vivo distribution in rat CNS (Kp,uBrain or Kp,uCSF) suggests a minor contribution of this efflux system to the CNS distribution of Quinolones.

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