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document
Pharmacokinetics and tolerance of single- and multiple-dose oral or intravenous linezolid , an oxazolidinone antibiotic , in healthy volunteers . AIMS To determine the pharmacokinetics and tolerance of oral and intravenous linezolid , an oxazolidinone antibiotic , in healthy volunteers following single- and multiple-dose administration . METHODS In two randomized , double-blind , placebo-controlled , dose-escalating trials , subjects were exposed either to oral ( 375 , 500 or 625 mg ) or intravenous ( 500 or 625 mg ) linezolid or placebo twice daily . Serial blood and urine samples were obtained after the first- and multiple-dose administrations for up to 18 days . Non-compartmental pharmacokinetic analyses were used to describe the disposition of linezolid . RESULTS Plasma linezolid concentrations and area under the concentration-time curves increased proportionally with dose irrespective of the route of administration . Plasma linezolid concentrations remained above the MIC90 for susceptible target pathogens ( 4.0 mg/L ) for the majority of the 12 h dosing interval . Mean clearance , half-life and volume of distribution were similar irrespective of dose for both the oral and intravenous routes . Linezolid was well tolerated and the frequency of drug-related adverse events was similar between the linezolid and placebo groups . CONCLUSIONS Oral and intravenous linezolid exhibit linear pharmacokinetics , with concentrations remaining above the target MIC90 for most of the dosing interval . These results support a twice-daily schedule for linezolid and demonstrate the feasibility of converting from intravenous to oral dosing without a dose adjustment .
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Intervention_Pharmacological
linezolid
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Intervention_Pharmacological
linezolid
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Intervention_Control
placebo-controlled
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Intervention_Pharmacological
linezolid
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Intervention_Control
placebo
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Intervention_Pharmacological
linezolid .
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Intervention_Pharmacological
linezolid
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Intervention_Pharmacological
linezolid
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Intervention_Pharmacological
Linezolid
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Intervention_Pharmacological
linezolid
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Intervention_Pharmacological
linezolid
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Outcome_Other
Pharmacokinetics
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Outcome_Adverse-effects
and
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Outcome_Other
tolerance
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Outcome_Physical
tolerance
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Outcome_Other
Serial blood and urine samples
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Outcome_Physical
pharmacokinetic analyses
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Outcome_Other
Plasma linezolid concentrations and area under the concentration-time curves
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Outcome_Other
Plasma linezolid concentrations
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Outcome_Other
Mean clearance , half-life and volume of distribution
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Outcome_Other
tolerated
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Outcome_Adverse-effects
frequency of drug-related adverse events
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Outcome_Other
linear pharmacokinetics
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Outcome_Other
target MIC90