Pharmacokinetics of Intravenously Administered Levofloxacin in Men and Women

Overholser, Brian R.; Kays, Michael B.; Lagvankar, Seema; Goldman, Mitchell; Mueller, Bruce A.; Sowinski, Kevin M.

doi:10.1592/phco.2005.25.10.1310

Cited by 11 publications

(10 citation statements)

References 23 publications

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“…Overholser et al compared the pharmacokinetics of intravenous LVX after a single 500 mg dose in men and women who showed no significant difference in body mass index, and observed that women had a 24% greater exposure (AUC) to LVX, with a significantly smaller V ss ( P <0.01) and a slower clearance ( P <0.01) 17. When pharmacokinetic parameters were adjusted for both lean and total body weight, the difference in clearance was attenuated, but V ss remained significantly smaller in women than in men, indicating a sex difference in V ss after intravenous administration of LVX.…”

Section: Resultsmentioning

confidence: 99%

Personalized therapeutics for levofloxacin: a focus on pharmacokinetic concerns

Gao¹,

Yu²,

Zeng³

et al. 2014

TCRM

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BackgroundPersonalized 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.MethodsRelevant 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.ResultsIn 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. Tr...

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Section: Resultsmentioning

confidence: 99%

Personalized therapeutics for levofloxacin: a focus on pharmacokinetic concerns

Gao¹,

Yu²,

Zeng³

et al. 2014

TCRM

View full text Add to dashboard Cite

show abstract

“…For some analgesics, anxiolytics and hypnotics, including certain benzodiazepines, drug plasma concentrations tend to be higher in women than in men. [14][15][16][17] Furthermore, drugs metabolised by hepatic oxidation have a prolonged elimination half-life in women taking contraceptives. [14] Some physiological differences related to gender may also influence drug metabolism, including muscle mass, hormonal status, disposition of the adipose tissue, gastric secretion and motility, and other physiological conditions such as the menstrual cycle and pregnancy.…”

Section: Pharmacological and Pharmacogenetic Differences Related To Gmentioning

confidence: 99%

Critical Considerations in Drug Development in Ethnically Diverse Populations

Benatar¹,

Lévy

2006

International Journal of Pharmaceutical Medicine

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“…Aufgrund der generell niedrigeren Körpermasse bei Frauen muss eine höhere Konzentration angenommen werden, wenn die Dosierung nicht adäquat an das Körpergewicht angepasst wird [12]. So wurden höhere Arzneimittelkonzentrationen bei Frauen häufi-ger gefunden [13]. Unter der Berücksichti-gung, dass eine eingeschränkte renale wie hepatische Funktion im Alter zu höheren Blut-und Plasmaspiegeln führt, war die Fläche unter den Konzentrations-ZeitKurven von Arzneistoffen bei geriatrischen Patienten weiterhin im Mittel erhöht [14].…”

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“…Demgegenüber lässt die Untersuchung aber auch den Schluss zu, dass QTc-Intervall-verlän-gernde Arzneistoffe von Frauen <60 Jahre noch relativ gut vertragen werden. Zumindest wurde bei der vorgegebenen Patientenzahl im Vergleich zu kritisch kranken Männern kein erhöhtes Risiko festgestellt (6/22 Frauen vs. 8/27 Männer).Unter der Berücksichtigung, dass eine eingeschränkte renale und hepatische Funktion im Alter sowie im kritischen Zustand zu höheren Blut-und Plasmaspiegeln führen dürfte, stehen die ermittelten Ergebnisse im Einklang mit der Annahme, dass v. a. bei Frauen mit niedrigerem Körpergewicht die üblichen Dosierungen, d. h. ohne Anpassung an das niedrige Körpergewicht, zu hohen Konzentrationen in Blut und Gewebe führen[12,13]. Dies sollte insbesondere dann klinisch bedeutsam werden, wenn sie schwer erkrankt sind und demzufolge nur noch wenige Kompensationsreserven besitzen.Als Indiz dafür, dass bei Frauen eine relative Überdosierung zumindest mitverantwortlich ist, spricht auch die Feststellung, dass schon die unter Therapie auswertbaren QTc-Intervalle (73%) bei Frauen zwischen Überleben und Versterben zu unterscheiden vermochten (p=0,014), insbesondere hinsichtlich der Entwicklung seit Aufnahme (p=0,001).…”

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