title: Assessment of pharmacokinetic proportionality of levofloxacin and cyclosporine over a 100-fold dose range in healthy human volunteers.
abstract: OBJECTIVE
  Levofloxacin and cyclosporine show different pharmacokinetic properties, but are known to be dose proportional within the therapeutic range. The authors evaluated the pharmacokinetic proportionality of levofloxacin and cyclosporine over a 100-fold dose range in healthy human volunteers, by liquid chromatography-tandem mass spectrometry (LC-MS/MS).
  
  
  METHODS
  Two independent, randomized, crossover studies were performed. For levofloxacin, eight volunteers were randomly assigned in a 1:1 ratio to receive a low dose (7.5 mg) orally or intravenously, followed by a 1-week washout period and administration via the alternate route. After another 1-week washout period, a therapeutic dose (750 mg) was administered to all eight subjects. For cyclosporine, another eight volunteers received a low dose (2 mg) or a therapeutic dose (200 mg) orally with a 1-week washout period. Drug concentrations were determined by LC-MS/MS.
  
  
  RESULTS
  For levofloxacin, the mean values for dose-normalized C(max) and AUC(last) with the two doses were as follows: therapeutic dose, 15.2 ± 4.6 ng/ml/mg and 103.6 ± 15.5 ng·h/ml/mg, respectively; low dose, 17.1 ± 6.5 ng/ml/mg and 72.6 ± 8.7 ng·h/ml/mg, respectively. For cyclosporine, the mean values for dose-normalized C(max) and AUC(last) were as follows: therapeutic dose, 4.9 ± 1.5 ng/ml/mg and 15.4 ± 4.9 ng·h/ml/mg, respectively; low dose, 1.6 ± 0.6 ng/ml/mg and 9.3 ± 7.3 ng·h/ml/mg, respectively.
  
  
  CONCLUSIONS
  In this study levofloxacin, which is completely absorbed and primarily eliminated renally without modification, showed better pharmacokinetic proportionality than cyclosporine, which is poorly absorbed and extensively metabolized.
authors.affiliation: Clinical Trial Center, Kyungpook National University Hospital, Daegu, Republic of Korea.
authors.forename: Mi-sun
authors.initials: MS
authors.lastname: Lim
authors.forename: Sook Jin
authors.initials: SJ
authors.lastname: Seong
authors.forename: Jeonghyeon
authors.initials: J
authors.lastname: Park
authors.forename: Jeong Ju
authors.initials: JJ
authors.lastname: Seo
authors.forename: Joomi
authors.initials: J
authors.lastname: Lee
authors.forename: Kyung-Sang
authors.initials: KS
authors.lastname: Yu
authors.forename: Hae Won
authors.initials: HW
authors.lastname: Lee
authors.forename: Young-Ran
authors.initials: YR
authors.lastname: Yoon
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001682:Biological Availability; D018592:Cross-Over Studies; D016572:Cyclosporine / Q000493:pharmacokinetics*; D004305:Dose-Response Relationship, Drug; D006207:Half-Life; D006801:Humans; D007166:Immunosuppressive Agents / Q000493:pharmacokinetics*; D007275:Injections, Intravenous; D064704:Levofloxacin; D008297:Male; D008875:Middle Aged; D015242:Ofloxacin / Q000493:pharmacokinetics*; D053719:Tandem Mass Spectrometry / Q000379:methods; D055815:Young Adult
chemical_list: D000900:Anti-Bacterial Agents; D007166:Immunosuppressive Agents; D064704:Levofloxacin; D016572:Cyclosporine; D015242:Ofloxacin