Personalized medicine should be encouraged because patients are complex, and this complexity results from
biological, medical (eg, demographics, genetics,
polypharmacy, and multimorbidities), socioeconomic, and cultural factors.
Levofloxacin (LVX) is a broad-spectrum
fluoroquinolone antibiotic. Awareness of personalized
therapeutics for LVX seems to be poor in clinical practice, and is reflected in prescribing patterns. Pharmacokinetic-pharmacodynamic studies have raised concerns about suboptimal patient outcomes with the use of LVX for some Gram-negative
infections. Meanwhile, new findings in LVX
therapeutics have only been sporadically reported in recent years. Therefore, an updated review on personalized LVX treatment with a focus on pharmacokinetic concerns is necessary.
METHODS: Relevant literature was identified by performing a PubMed search covering the period from January 1993 to December 2013. We included studies describing dosage adjustment and factors determining LVX pharmacokinetics, or pharmacokinetic-pharmacodynamic studies exploring how best to prevent the emergence of resistance to LVX. The full text of each included article was critically reviewed, and data interpretation was performed.
RESULTS: In addition to limiting the use of
fluoroquinolones, measures such as reducing the breakpoints for antimicrobial susceptibility testing, choice of high-dose short-course of once-daily LVX regimen, and tailoring LVX dose in special patient populations help to achieve the validated pharmacokinetic-pharmacodynamic target and combat the increasing LVX resistance. Obese individuals with normal renal function cleared LVX more efficiently than normal-weight individuals. Compared with the scenario in healthy subjects, standard 2-hour spacing of
calcium formulations and oral LVX was insufficient to prevent a chelation interaction in
cystic fibrosis patients. Inconsistent conclusions were derived from studies of the influence of sex on the pharmacokinetics of LVX, which might be associated with sample size and administration route. Children younger than 5 years cleared LVX nearly twice as fast as adults. Patients in
intensive care receiving LVX
therapy showed significant pharmacokinetic differences compared with healthy subjects.
Creatinine clearance explained most of the population variance in the plasma clearance of LVX. Switching from intravenous to oral delivery of LVX had economic benefits. Addition of
tamsulosin to the LVX regimen was beneficial for patients with bacterial
prostatitis because
tamsulosin could increase the maximal concentration of LVX in prostatic tissue. Coadministration of multivalent
cation-containing drugs and LVX should be avoided. For patients receiving
warfarin and LVX concomitantly, caution is needed regarding potential changes in the international normalized ratio; however, it is unnecessary to seek alternatives to LVX for the sake of avoiding drug interaction with
warfarin. It is unnecessary to proactively reduce the dose of
cyclosporin or
tacrolimus when comedicated with LVX. Transporters such as organic
anion-transporting
polypeptide 1A2,
P-glycoprotein, human
organic cation transporter 1, and multidrug and toxin extrusion
protein 1 are involved in the pharmacokinetics of LVX.
CONCLUSION: Personalized LVX
therapeutics are necessary for the sake of better safety, clinical success, and avoidance of resistance. New findings regarding individual dosing of LVX in special patient populations and active transport mechanisms in vivo are opening up new horizons in clinical practice.