Personalized therapeutics for levofloxacin: a focus on pharmacokinetic concerns

Figures & data

Table 1 Pharmacokinetic concerns in personalized therapeutics for levofloxacin in specific patient populations

Specific patient population	Pharmacokinetic alternations	Medication therapy management
Obese versus normal-weight	Marked variability in levofloxacin clearance was evident in the obese population. Obese individuals with normal renal function may clear levofloxacin more efficiently than normal-weight individuals.^Citation9	Clinicians should be mindful of the potential variability in drug exposure in obese individuals and consider the potential impact of underdosing. Moxifloxacin may be an alternative to levofloxacin if clinically indicated.
Cystic fibrosis versus noncystic fibrosis	Standard 2-hour spacing of calcium formulation and levofloxacin was insufficient to prevent a chelation interaction in patients with cystic fibrosis. Oral absorption of levofloxacin is slower among patients with cystic fibrosis when compared with patients without cystic fibrosis.^Citation10	Multivalent cations should be maximally separated from oral levofloxacin administration.
Male versus female	Package insert of LVX does not have any mention of sex-specific differences in pharmacokinetics. Two studies reported no influence of sex on oral LVX pharmacokinetics; however, one study found that vss remained significantly smaller in women compared with men when pharmacokinetic parameters of intravenous LVX were adjusted for body weight.^Citation11 Inconsistent conclusions might be associated with sample size and administration route.	It is necessary to address whether sex has influences on the pharmacokinetics, efficacy, and toxicity of LVX by conducting future studies with larger sample sizes.
Children versus adults	Children younger than 5 years cleared levofloxacin nearly twice as fast as adults and, as a result, have total systemic exposure (ie, AUC) approximately one half that of adults.^Citation12	Children ≥5 years need a daily dose of 10 mg/kg, whereas children 6 months to <5 years should receive 10 mg/kg every 12 hours.
Elderly patients versus younger patients	Levofloxacin 500 mg once daily yielded probabilities of achieving AUC0–24/MIC of 30 of 95.7% for elderly patients (≥65 years) compared with 72.7% for younger patients (<65 years). Levofloxacin pharmacokinetics in elderly patients with community-acquired pneumonia are markedly different from those in younger patients.^Citation13	Levofloxacin administered at a dose of 750 mg once daily results in a high probability of target attainment and improved bacteriological outcome against S. pneumoniae in patients with community-acquired pneumonia.
Intensive care patients	ICU patients on levofloxacin showed significant pharmacokinetic differences compared with healthy subjects. The mean steady-state total body exposure to levofloxacin in ICU patients treated for early-onset ventilator-associated pneumonia during the 12-hour dosage interval was about 30%–40% lower than in healthy volunteers.^Citation14	IV levofloxacin 500 mg twice daily is suitable in the treatment of early-onset ventilator-associated pneumonia in ICU patients with normal renal function.
Patients with creatinine clearance less than 50 mL per minute	Creatinine clearance explained most of the population variance in plasma clearance of levofloxacin.^Citation15	Levofloxacin dosage adjustment should be individualized on the basis of creatinine clearance, especially in those with creatinine clearance less than 50 mL per minute.

Abbreviations: AUC, area under the plasma concentration-time curve; V_ss, steady-state volume of distribution; ICU, intensive care unit; AUC_0–24/MIC, the ratio of area under the concentration-time curve for 24 hours to minimum inhibitory concentration; LVX, levofloxacin; IV, intravenous.

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