Population Pharmacokinetics and Use of Monte Carlo Simulation To Evaluate Currently Recommended Dosing Regimens of Ciprofloxacin in Adult Patients with Cystic Fibrosis

Pharmacodynamic data on ciprofloxacin indicate that a target area under the concentration-time curve from 0 to 24 h (AUC(0–24))/MIC ratio of ≥125 is necessary to achieve optimal bactericidal activity for the treatment of gram-negative pneumonia. The purpose of this prospective study was to (i) develop a pharmacokinetic (PK) model to be utilized for therapeutic drug monitoring (TDM) of ciprofloxacin and (ii) evaluate current ciprofloxacin dosing regimens for pneumonias in cystic fibrosis (CF) patients. Twelve adult CF patients received a single 400-mg dose of IV ciprofloxacin. Six blood samples were obtained over a 12-h interval. Serum drug concentrations were determined by high-pressure liquid chromotography and were fitted to one- and two-compartment models by using NPEM2. Ciprofloxacin MIC data for Pseudomonas aeruginosa were obtained from 1,213 CF patients enrolled in a large clinical trial. A Monte Carlo simulation was performed to estimate the fractional attainment of an AUC(0–24)/MIC ratio of ≥125. A two-compartment model best describes the serum drug concentration data. The mean fitted PK parameter values are volume of distribution in the central compartment, 0.29 liter/kg; volume of distribution at steady state, 1.1 liters/kg; total clearance, 0.34 liter/h/kg; distributional clearance, 0.89 liter/h/kg; half-life at α phase, 0.16 h; and half-life at β phase, 2.9 h. The overall fractional attainment of achieving an AUC(0–24)/MIC ratio of ≥125 against P. aeruginosa isolates with ciprofloxacin (400 mg every 12 h [q12h] and 8 qh) were 10 and 30%, respectively. A clinical breakpoint MIC of <0.5 μg/ml for susceptibility is suggested, based on an examination of the fractional attainment of the AUC(0–24)/MIC target at each MIC. The recommended doses of 400 mg q8h or q12h may be inadequate to treat an acute pulmonary exacerbation when given alone. The poor and variable AUC(0–24)/MIC ratios support the use of TDM to monitor and adjust the dosage to optimize the efficacy of ciprofloxacin therapy in these patients

Luminescent Zinc(II) Complexes of Fluorinated Benzothiazol-2-yl Substituted Phenoxide and Enolate Ligands

Zn­(II) complexes of the following new, fluorine-containing, benzothiazole-derived ligands have been synthesized and characterized crystallographically: 2-(3,3,3-trifluoro-2-oxopropyl)­benzothiazole (<b>3</b>), 4,5,6,7-tetrafluoro-2-(3,3,3-trifluoro-2-oxopropyl)­benzothiazole (<b>4</b>), 4,5,6,7-tetrafluoro-2-(2-hydroxyphenyl)­benzothiazole (<b>12</b>), 2-(3,4,5,6-tetrafluoro-2-hydroxyphenyl)-4,5,6,7-tetrafluorobenzothiazole (<b>13</b>), and 2-(3,4,5,6-tetrafluoro-2-hydroxyphenyl)­benzothiazole (<b>16</b>); the Cu­(II) complex of ligand <b>4</b> is also reported. These are analogs of the important photo- and electroluminescent material [Zn­(BTZ)₂]₂, where H-BTZ = 2-(2-hydroxyphenyl)­benzothiazole. DFT calculations indicate that HOMO and LUMO energy levels in these materials are substantially lowered by fluorination. The fluorinated ZnL₂ complexes are mononuclear (in contrast to the dinuclear, nonfluorinated material [Zn­(BTZ)₂]₂). They easily sublime and show broad visible photoluminescence. A common crystallographic feature is the existence of pairs of fluorinated ZnL₂ molecules related by inversion centers, with their π systems facing one another

Luminescent Zinc(II) Complexes of Fluorinated Benzothiazol-2-yl Substituted Phenoxide and Enolate Ligands

Zn­(II) complexes of the following new, fluorine-containing, benzothiazole-derived ligands have been synthesized and characterized crystallographically: 2-(3,3,3-trifluoro-2-oxopropyl)­benzothiazole (<b>3</b>), 4,5,6,7-tetrafluoro-2-(3,3,3-trifluoro-2-oxopropyl)­benzothiazole (<b>4</b>), 4,5,6,7-tetrafluoro-2-(2-hydroxyphenyl)­benzothiazole (<b>12</b>), 2-(3,4,5,6-tetrafluoro-2-hydroxyphenyl)-4,5,6,7-tetrafluorobenzothiazole (<b>13</b>), and 2-(3,4,5,6-tetrafluoro-2-hydroxyphenyl)­benzothiazole (<b>16</b>); the Cu­(II) complex of ligand <b>4</b> is also reported. These are analogs of the important photo- and electroluminescent material [Zn­(BTZ)₂]₂, where H-BTZ = 2-(2-hydroxyphenyl)­benzothiazole. DFT calculations indicate that HOMO and LUMO energy levels in these materials are substantially lowered by fluorination. The fluorinated ZnL₂ complexes are mononuclear (in contrast to the dinuclear, nonfluorinated material [Zn­(BTZ)₂]₂). They easily sublime and show broad visible photoluminescence. A common crystallographic feature is the existence of pairs of fluorinated ZnL₂ molecules related by inversion centers, with their π systems facing one another