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.
Original language | English |
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Pages (from-to) | 256-268 |
Number of pages | 13 |
Journal | British Journal of Clinical Pharmacology |
Volume | 81 |
Issue number | 2 |
DOIs | |
Publication status | Published - Feb-2016 |
Externally published | Yes |
Keywords
- Administration, Oral
- Adolescent
- Adult
- Anti-Bacterial Agents
- Circadian Rhythm
- Computer Simulation
- Cross-Over Studies
- Dose-Response Relationship, Drug
- Electrocardiography
- Glomerular Filtration Rate
- Humans
- Levofloxacin
- Male
- Middle Aged
- Models, Biological
- Thyrotropin
- Young Adult
- Journal Article
- Randomized Controlled Trial