Identifying 24 h variation in the pharmacokinetics of levofloxacin: a population pharmacokinetic approach.
Br J Clin Pharmacol
; 81(2): 256-68, 2016 Feb.
Article
en En
| MEDLINE
| ID: mdl-26852745
ABSTRACT
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.Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Ritmo Circadiano
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Levofloxacino
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Antibacterianos
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Modelos Biológicos
Tipo de estudio:
Clinical_trials
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Prognostic_studies
Límite:
Adolescent
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Adult
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Br J Clin Pharmacol
Año:
2016
Tipo del documento:
Article