In vivo tissue pharmacokinetics by fluorine magnetic resonance spectroscopy: A study of liver and muscle disposition of fleroxacin in humans

Abstract

Magnetic resonance spectroscopy of fluorine (19F) has been used to noninvasively study the in vivo pharmacokinetics of a model drug, fleroxacin (a fluoroquinolone antibiotic agent), in healthy human subjects. After oral administration, fleroxacin was detected in 19F magnetic resonance spectra from both liver and calf muscle and four magnetic resonance examinations were undertaken during a 24-hour period. By combining plasma analysis by high performance liquid chromatography with the magnetic resonance data, the following pharmacokinetic parameters (mean values) were obtained: tmax, 1.4, 4.6, and 5.6 hours in liver, plasma, and muscle, respectively; Cmax, 53, about 250, and about 60 mumol/L in plasma, liver, and muscle, respectively; t1/2, 4.4 hours (fast phase) and 10.8 hours (slow phase) in liver and 14.2 hours in plasma. The study documents for the first time the potential use of 19F magnetic resonance spectroscopy to noninvasively observe the time-related changes of a fluorine-containing drug in human tissues after oral administration.

Issues in Pharmacokinetics and Pharmacodynamics of Anti-Infective Agents: Distribution in Tissue

“…A class of compounds that follows similar patterns for PET studies are the fluorinated quinolones, and studies were performed with trovafloxacin (57) (Fig. 1), lomefloxacin (158), and fleroxacin (83). Although these measurements would be useful for many other drugs, the requirement of devising new synthetic procedures is a major limitation.…”

“…(i) Imaging techniques. As a conceptual extension of autoradiography (7,145,173), several novel imaging methods that lend themselves to the study of drug distribution in humans were developed (26,53,55,56,57,61,64,74,77,83,88,128,147,150,156,158,182,187). These comprised radiopharmaceutical techniques, such as two-dimensional planar gamma scintigraphy (PGS) (88,174), and three-dimensional techniques, such as single photon emission computed tomography (SPECT) (26,61,77,182), positron emission tomography (PET) (56,57,128,188) (Fig.…”

“…These comprised radiopharmaceutical techniques, such as two-dimensional planar gamma scintigraphy (PGS) (88,174), and three-dimensional techniques, such as single photon emission computed tomography (SPECT) (26,61,77,182), positron emission tomography (PET) (56,57,128,188) (Fig. 1), and magnetic resonance spectroscopy (MRS) (83,129,187), which does not require radioactive labeling. Although these techniques mainly were introduced to clinical medicine for various diagnostic purposes (150) and for the study of tissue metabolism and blood flow (128), they also opened a unique opportunity for PK research.…”

“…1) and that target site drug levels may substantially differ from corresponding plasma drug levels (15,16,22,55,57,63,65,78,80,81,83,108,109,116,188). Suboptimal target site concentrations may have important clinical implications, as they may explain therapeutic failures (22,80,129), in particular, for bacteria for which in vitro MICs are high (22,80); in addition, it is conceivable that subinhibitory concentrations in tissues may also trigger bacterial resistance (76,87,117,120).…”

VatuximabTM: Optimizing Therapeutic Strategies for Prostate Cancer Based on Dynamic MR Tumor Oximetry

“…Other studies have examined fluoroquinolone antibiotics (fleroxacin) [166], antimicrobials (sitafloxacin) [66], nonsteroidal anti-inflammatory (niflumic acid [67]), and anti-histamines (tecastemizole [68]). However, the tecastemizole was only detected from 3 of 23 patients and the retention was found to be much shorter than the psychotropic drugs such as fluoxetine.…”