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Identifying 24 h variation in the pharmacokinetics of levofloxacin: a population pharmacokinetic approach.
Kervezee, Laura; Stevens, Jasper; Birkhoff, Willem; Kamerling, Ingrid M C; de Boer, Theo; Dröge, Melloney; Meijer, Johanna H; Burggraaf, Jacobus.
Afiliación
  • Kervezee L; Laboratory for Neurophysiology, Department of Molecular Cell Biology, Leiden University Medical Center, Leiden.
  • Stevens J; Centre for Human Drug Research, Leiden.
  • Birkhoff W; Centre for Human Drug Research, Leiden.
  • Kamerling IM; Centre for Human Drug Research, Leiden.
  • de Boer T; Centre for Human Drug Research, Leiden.
  • Dröge M; ABL Laboratories, Assen, the Netherlands.
  • Meijer JH; ABL Laboratories, Assen, the Netherlands.
  • Burggraaf J; Laboratory for Neurophysiology, Department of Molecular Cell Biology, Leiden University Medical Center, Leiden.
Br J Clin Pharmacol ; 81(2): 256-68, 2016 Feb.
Article en En | MEDLINE | ID: mdl-26852745
AIM: The objective of this study was to investigate whether the pharmacokinetics of orally administered levofloxacin show 24 h variation. Levofloxacin was used as a model compound for solubility and permeability independent absorption and passive renal elimination. METHODS: In this single centre, crossover, open label study, 12 healthy subjects received an oral dose of 1000 mg levofloxacin at six different time points equally divided over the 24 h period. Population pharmacokinetic modelling was used to identify potential 24 h variation in the pharmacokinetic parameters of this drug. RESULTS: The pharmacokinetics of levofloxacin could be described by a one compartment model with first order clearance and a transit compartment to describe drug absorption. The fit of the model was significantly improved when the absorption rate constant was described as a cosine function with a fixed period of 24 h, a relative amplitude of 47% and a peak around 08.00 h in the morning. Despite this variation in absorption rate constant, simulations of a once daily dosing regimen showed that tmax , Cmax and the area under the curve at steady-state were not affected by the time of drug administration. CONCLUSION: The finding that the absorption rate constant showed considerable 24 h variation may be relevant for drugs with similar physicochemical properties as levofloxacin that have a narrower therapeutic index. Levofloxacin, however, can be dosed without taking into account the time of day, at least in terms of its pharmacokinetics.
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Ritmo Circadiano / Levofloxacino / Antibacterianos / Modelos Biológicos Tipo de estudio: Clinical_trials / Prognostic_studies Límite: Adolescent / Adult / Humans / Male / Middle aged Idioma: En Revista: Br J Clin Pharmacol Año: 2016 Tipo del documento: Article

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Ritmo Circadiano / Levofloxacino / Antibacterianos / Modelos Biológicos Tipo de estudio: Clinical_trials / Prognostic_studies Límite: Adolescent / Adult / Humans / Male / Middle aged Idioma: En Revista: Br J Clin Pharmacol Año: 2016 Tipo del documento: Article