Abstract:
:This study developed a physiologically based pharmacokinetic (PBPK) model in intraabdominally infected rats and extrapolated it to humans to predict the levofloxacin pharmacokinetics and penetration into tissues. Twelve male rats with intraabdominal infections induced by Escherichia coli received a single dose of 50 mg/kg body weight of levofloxacin. Blood plasma was collected at 5, 10, 20, 30, 60, 120, 240, 480 and 1440 min after injection, respectively. A PBPK model was developed in rats and extrapolated to humans using GastroPlus software. The predictions were assessed by comparing predictions and observations. In the plasma concentration-versus-time profile of levofloxacin in rats, C max was 23.570 μg/ml at 5 min after intravenous injection, and t1/2 was 2.38 h. The plasma concentration and kinetics in humans were predicted and validated by the observed data. Levofloxacin penetrated and accumulated with high concentrations in the heart, liver, kidney, spleen, muscle and skin tissues in humans. The predicted tissue-to-plasma concentration ratios in abdominal viscera were between 1.9 and 2.3. When rat plasma concentrations were known, extrapolation of a PBPK model was a method to predict the drug pharmacokinetics and penetration in humans. Levofloxacin had good penetration into the liver, kidney and spleen as well as other tissues in humans. This pathological model extrapolation may provide a reference for the study of antiinfective PK/PD. In our study, levofloxacin penetrated well into abdominal organs. Also ADR monitoring should be implemented when using levofloxacin.
journal_name
Eur J Drug Metab Pharmacokinetjournal_title
European journal of drug metabolism and pharmacokineticsauthors
Zhu L,Zhang Y,Yang J,Wang Y,Zhang J,Zhao Y,Dong Wdoi
10.1007/s13318-015-0271-8subject
Has Abstractpub_date
2016-08-01 00:00:00pages
395-402issue
4eissn
0378-7966issn
2107-0180pii
10.1007/s13318-015-0271-8journal_volume
41pub_type
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journal_title:European journal of drug metabolism and pharmacokinetics
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journal_title:European journal of drug metabolism and pharmacokinetics
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