Pharmacokinetics Of Levofloxacin Research Articles

Pharmacokinetics of Azithromycin, Levofloxacin, and Ofloxacin in Rabbit Extraocular Tissues After Ophthalmic Administration.

IntroductionAzithromycin demonstrates high tissue distribution and prolonged elimination half-life. In this study, we monitored the pharmacokinetics of a single ophthalmic administration of 1% azithromycin ophthalmic solution containing polycarbophil in the extraocular tissues, including the eyelid, and compared it with that of two commercial ophthalmic products, 1.5% levofloxacin ophthalmic solution and 0.3% ofloxacin ophthalmic ointment.MethodsRabbits were treated with either a single topical administration of 1% azithromycin ophthalmic solution, 1.5% levofloxacin ophthalmic solution, or 0.3% ofloxacin ophthalmic ointment. The eyelid, conjunctiva, and cornea were collected at 0.25, 0.5, 1, 2, 4, 8, and 24 h post-administration. Tissue samples were pretreated for drug concentration measurements by ultra-performance liquid chromatography-tandem mass spectrometry. Pharmacokinetic parameters were determined by non-compartmental analysis.ResultsAzithromycin was rapidly absorbed, and its levels remained near the observed maximum concentrations for up to 24 h post-administration in all tissue. In contrast, extraocular tissue concentrations of levofloxacin and ofloxacin decreased with time. The maximum concentrations of azithromycin, levofloxacin, and ofloxacin were 35.6, 34.1, and 55.1 µg/g in the eyelid, 44.2, 46.8, and 20.4 µg/g in the conjunctiva, and 79.9, 18.0, and 2.21 µg/g in the cornea, respectively. The values of the area under the curve from 0 to 24 h after administration of azithromycin, levofloxacin, and ofloxacin were 602, 58.5, and 267 µg·h/g in the eyelid, 837, 43.2, and 51.9 µg·h/g in the conjunctiva, and 1250, 26.4, and 5.46 µg h/g in the cornea, respectively.ConclusionThe drug concentrations of azithromycin and levofloxacin were relatively comparable among the extraocular tissues following topical administration of the respective ophthalmic solutions, whereas the concentrations of ofloxacin varied following dosing of its ophthalmic ointment. The slow elimination profile in any extraocular tissue of rabbits was unique to azithromycin, and led to the demonstration of high exposures of azithromycin in all extraocular tissues after ophthalmic administration.FundingThis research and Rapid Service Fees were supported by Senju Pharmaceutical Co., Ltd.

Pharmacokinetics of Levofloxacin in Children Treated for Exposure to Drug-Resistant Tuberculosis.

Levofloxacin is used to treat and prevent drug-resistant tuberculosis in children. We assessed levofloxacin serum drug concentrations in 24 children aged 2 to 10 years who received levofloxacin-based tuberculosis preventive therapy in Karachi, Pakistan. Only 9 children (37.5%) achieved adequate drug exposure. Target serum drug concentration was met in 4 (26.7%) of 15 children dosed consistently with World Health Organization recommendations and 4 (80.0%) of 5 who received higher-than-recommended doses. Levofloxacin dosing recommendations may require reevaluation.

Pharmacokinetics of levofloxacin after single intravenous, oral and subcutaneous administration to dogs

The pharmacokinetic properties of the fluoroquinolone levofloxacin (LFX) were investigated in six dogs after single intravenous, oral and subcutaneous administration at a dose of 2.5, 5 and 5mg/kg, respectively. After intravenous administration, distribution was rapid (T½dist 0.127±0.055hr) and wide as reflected by the volume of distribution of 1.20±0.13L/kg. Drug elimination was relatively slow with a total body clearance of 0.11±0.03Lkg-1 hr-1 and a T½ for this process of 7.85±2.30hr. After oral and subcutaneous administration, absorption half-life and Tmax were 0.35 and 0.80hr and 1.82 and 2.82hr, respectively. The bioavailability was significantly higher (p˂0.05) after subcutaneous than oral administration (79.90 vs. 60.94%). No statistically significant differences were observed between other pharmacokinetic parameters. Considering the AUC24hr /MIC and Cmax /MIC ratios obtained, it can be concluded that LFX administered intravenously (2.5mg/kg), subcutaneously (5mg/kg) or orally (5mg/kg) is efficacious against Gram-negative bacteria with MIC values of 0.1μg/ml. For Gram-positive bacteria with MIC values of 0.5μg/kg, only SC and PO administration at a dosage of 5mg/kg showed to be efficacious. MIC-based PK/PD analysis by Monte Carlo simulation indicates that the proposed dose regimens of LFX, 5 and 7.5mg/kg/24hr by SC route and 10mg/kg/24hr by oral route, in dogs may be adequate to recommend as an empirical therapy against S.aureus strains with MIC≤0.5μg/ml and E.coli strains with MIC values ≤0.125μg/ml.

Population Pharmacokinetics of Levofloxacin in Plasma and Bone of Patients Undergoing Hip or Knee Surgery.

Patients undergoing hip or knee replacement therapy are routinely pretreated with antibiotics before they enter the operation theater. This treatment intends to reduce the incidence of peri- or postsurgical infections. Here, we calculated the uptake kinetics of levofloxacin into bone to see whether levofloxacin could be obtained from the trabecular and cortical bone and at what time concentrations are sufficiently high to inhibit the usual hospital infections. Patients (n= 42) undergoing routine surgery were treated with 500mg levofloxacin intravenously immediately prior to the operation. Plasma samples were taken before and at 3 points after termination of drug infusion. After replacement of the bones, extracts were obtained from them. Levofloxacin was quantified using high-performance liquid chromatography. The kinetics of levofloxacin and its distribution into bone were analyzed using a population approach (ADAPT5). Clearance was 14.0 L/h, and distribution volume was 77 L. Bone uptake t½ was calculated as 4.2 and 5.4hours for cortical bone and trabecular bone, respectively. In knee samples (but not in hip samples), we noted that the cortical bone contained higher levels of levofloxacin than the trabecular bone. From our data, we can conclude that levofloxacin might be useful for prophylactic use in bone surgery.

Pharmacokinetics of levofloxacin after single intravenous and subcutaneous administration in domestic goats (Capra hircus): a pilot study

Pharmacokinetics of levofloxacin after single intravenous and subcutaneous administration in domestic goats (Capra hircus): a pilot study

Pharmacokinetics of Levofloxacin in Multidrug- and Extensively Drug-Resistant Tuberculosis Patients.

Pharmacodynamics are especially important in the treatment of multidrug- and extensively drug-resistant tuberculosis (M/XDR-TB). The free area under the concentration time curve in relation to MIC (fAUC/MIC) is the most relevant pharmacokinetic (PK)-pharmacodynamic (PD) parameter for predicting the efficacy of levofloxacin (LFX). The objective of our study was to assess LFX PK variability in M/XDR-TB patients and its potential consequence for fAUC/MIC ratios. Patients with pulmonary M/XDR-TB received LFX as part of the treatment regimen at a dose of 15 mg/kg administered once daily. Blood samples obtained at steady state before and 1, 2, 3, 4, 7, and 12 h after drug administration were measured by validated liquid chromatography-tandem mass spectrometry. The MIC values of LFX were determined by the agar dilution method on Middlebrook 7H10 and the MGIT960 system. Twenty patients with a mean age of 31 years (interquartile range [IQR] = 27 to 35 years) were enrolled in this study. The median AUC0-24 was 98.8 mg/h/liter (IQR = 84.8 to 159.6 mg/h/liter). The MIC median value for LFX was 0.5 mg/liter with a range of 0.25 to 2.0 mg/liter, and the median fAUC0-24/MIC ratio was 109.5 (IQR = 48.5 to 399.4). In 4 of the 20 patients, the value was below the target value of ≥100. When MICs of 0.25, 0.5, 1.0, and 2.0 mg/liter were applicable, 19, 18, 3, and no patients, respectively, had an fAUC/MIC ratio that exceeded 100. We observed a large variability in AUC. An fAUC0-24/MIC of ≥100 was only observed when the MIC values for LFX were 0.25 to 0.5 mg/liter. Dosages exceeding 15 mg/kg should be considered for target attainment if exposures are assumed to be safe. (This study has been registered at ClinicalTrials.gov under registration no. NCT02169141.).

Clinical pharmacokinetics of oral levofloxacin and sitafloxacin inepididymal tissue.

This study aimed to investigate the penetration of fluoroquinolones into human epididymal tissue. The penetration of levofloxacin (LVFX) 500mg or sitafloxacin (STFX) 100mg into epididymal tissue was examined. Patients with prostate cancer who were referred for orchiectomy were included. LVFX 500mg (n=9) or STFX 100mg (n=9) was administered orally 1h before orchiectomy, and 0.5g of epididymal tissue and blood samples were collected simultaneously during surgery. Drug concentrations were measured by high-performance liquid chromatography, and patient characteristics and adverse events were analyzed. The mean ratio of the epididymal concentration to the serum concentration was 1.48±0.45 for LVFX and 1.54±0.81 for STFX. For LVFX, the simulated curves estimated the following: maximum concentrations (Cmax) of 8.84μg/ml in serum and 14.1μg/g in epididymal tissue and area under the concentration-time curve for 24h (AUC24) of 68.5μgh/ml in serum and 108.9μgh/g in epididymal tissue. For STFX, the Cmax was 1.22μg/ml in serum and 1.66μg/g in epididymal tissue, and the AUC24 was 9.58μgh/ml in serum and 13.1μgh/g in epididymal tissue. Neither treatment-related adverse events nor postoperative urogenital infections were observed. The results of this study suggest that oral administration of LVFX 500mg or STFX 100mg achieves effective epididymal concentrations for treatment of epididymitis.

Pulmonary pharmacokinetics of levofloxacin in rats after aerosolization of immediate-release chitosan or sustained-release PLGA microspheres

A comparative pharmacokinetic study was conducted in rats after intratracheal aerosolization of levofloxacin, as a solution, as immediate-release chitosan microspheres or as sustained-release PLGA microspheres. A pharmacokinetic model was constructed to model levofloxacin concentrations both in plasma and in the lung epithelial lining fluid (ELF). The plasma and ELF experimental concentration profiles versus time were similar for the intravenous and intratracheal levofloxacin solutions and for the intratracheal levofloxacin-loaded chitosan microsphere dry powder, indicating that levofloxacin diffused almost instantaneously through the broncho-alveolar barrier and that the chitosan microspheres released levofloxacin very rapidly, as anticipated from in vitro release studies. The bioavailability for the intratracheal levofloxacin solution and intratracheal chitosan microspheres was estimated to be 98% and 71%, respectively, both with a direct release into the ELF compartment. The ELF-to-unbound plasma AUC ratios were slightly above 2 and may result from an efflux transport. For the intratracheal PLGA microspheres, a high ELF-to-unbound plasma AUC concentration ratio (311) was observed and high levofloxacin concentrations were maintained in ELF for at least 72h in consistency with the in vitro release studies. The bioavailability was 92%, with 19% of the dose released immediately (burst release) into the ELF and 73% released slowly into the ELF from a depot compartment, i.e. the PLGA microspheres, according to a Weibull model. These results highlight the benefit of using sustained-release microspheres administered as aerosols to provide and to maintain high pulmonary concentrations of an antibiotic characterized with a high permeability profile through the broncho-alveolar barrier. The sustained-release microsphere dry powder aerosol may therefore provide advantages over solutions or pure drug dry powders for inhalation in terms of treatment efficiency, ease of use and frequency of administration.

Predictions of the Pharmacokinetics in Burn Injury Patients using Regression Models - Case Study with Levofloxacin.

Owing to its excellent safety, tolerability, pharmacokinetic and pharmacodynamic profile levofloxacin is widely used. Although pharmacokinetics of levofloxacin was somewhat more variable in burn injury patients, it appeared to be comparable to healthy subjects or other patients. Linear regression model was established for Cmax or Cmin vs. [AUCtau, CL and Vd] of levofloxacin using individual values from burn injury patients. Appropriate regression lines for Cmax or Cmin were subjected to internal and external validation on the ability to predict CL, Vd and AUCtau parameters. The mean absolute error (MAE) and root mean square error (RMSE) of the predictions were used to judge the appropriateness of either Cmax or Cmin models. Cmax models developed for levofloxacin showed moderate to strong correlations with the various parameters such as CL, Vd and AUCtau. The Cmin models showed strong correlation for CL and AUCtau but not for Vd where the correlation was weak. Internal validation using data from individual burn patients showed RMSE of 13.47-25.42% for various predictions. External validation that used mean data from healthy subjects showed RMSE of 13.86-27.13%. Despite the pharmacokinetic variability, linear regression models using either Cmax or Cmin were established for levofloxacin rendering predictions of several key pharmacokinetic parameters. Although there was limitation of Cmin model for predicting Vd, both models may be used as a prospective tool for the prediction of levofloxacin pharmacokinetics in burn care patients.

Population pharmacokinetics of levofloxacin in Korean patients

Levofloxacin (LVFX) has different effects depending on the area under the concentration–time curve (AUC)/minimum inhibitory concentration (MIC) ratio. While AUC can be expressed as dose/clearance (CL), we measured serial concentrations of LVFX in Koreans and tried to set a Korean-specific equation, estimating the CL of the antibiotic. In total, 38 patients, aged 18–87 years, received once daily intravenous LVFX doses of 500 mg or 250 mg, depending on their renal function. Four plasma samples were obtained according to a D optimal sampling design. The population pharmacokinetic (PK) parameters of LVFX were estimated using non-linear mixed-effect modeling (NONMEM, ver. 7.2). The CL of LVFX was dependent on creatinine clearance (CLCR) as a covariate. The mean population PK parameters of LVFX in Koreans were as follows: CL (l/hour) = 6.19 × (CLCR/75)1.32. The CL of LVFX in Koreans is expected to be lower than that in Western people.

Pharmacokinetic/pharmacodynamic-based optimization of levofloxacin administration in the treatment of MDR-TB

The emergence of MDR-TB and XDR-TB has complicated TB treatment success. Among many factors that contribute to the development of resistance, low drug exposure is not the least important. This review summarizes the available information on pharmacokinetic properties of levofloxacin in relation to microbial susceptibilities, in order to optimize the dose and make general treatment recommendations. A total of 37 studies on adult (32 studies) and paediatric (5 studies) MDR-TB patients were included. Among the 32 adult studies, 19 were on susceptibility of Mycobacterium tuberculosis isolates to levofloxacin by MIC, 1 was on susceptibility of M. tuberculosis isolates to levofloxacin by MBC, 1 was on susceptibility of M. tuberculosis isolates to levofloxacin by mutant prevention concentration and 4 were on pharmacokinetics of levofloxacin, and 7 others were included. Likewise, out of five studies on children, two dealt with levofloxacin pharmacokinetic parameters, one reviewed CSF concentrations and two dealt with background information. In adult MDR-TB patients, standard dosing of once-daily 1000 mg levofloxacin in TB treatment did not consistently attain the target concentration (i.e. fAUC/MIC >100 and fAUC/MBC >100) in 80% of the patients with MIC and MBC of 1 mg/L, leaving them at risk of developing drug resistance. However, with an MIC of 0.5 mg/L, 100% of the patients achieved the target concentration. Similarly, paediatric patients failed consistently in achieving given pharmacokinetic/pharmacodynamic targets due to age-related differences, demanding a shift towards once daily dosing of 15-20 mg/kg. Therefore, we recommend therapeutic drug monitoring for patients with strains having MICs of ≥0.5 mg/L and suggest revising the cut-off value from 2 to 1 mg/L.

Pharmacokinetics and aqueous humor penetration of levofloxacin 1.5% and moxifloxacin 0.5% in patients undergoing cataract surgery.

PurposeThe objective of this study was to compare the pharmacokinetics of levofloxacin 1.5% and moxifloxacin hydrochloride 0.5% ophthalmic solutions in aqueous humor after multiple doses prior to cataract surgery.MethodsNinety-eight eyes underwent cataract surgery and met the requirements of PK analysis. Eligible eyes were randomly assigned in a 1:1 ratio to receive levofloxacin or moxifloxacin prior to cataract surgery and were randomized into one of four sampling time points (ie, 1, 2, 4, and 6 hour post-last dose). Randomization was investigator and laboratory-masked. Three days prior to cataract surgery, each patient instilled one drop of the assigned study medication into the operative eye four times daily. One aqueous humor specimen was collected from the eye at the randomized time point. Aqueous humor specimens were assayed for drug concentration using a validated liquid chromatography and tandem mass spectrometer.ResultsConcentrations of the drug in the aqueous humor, as described by mean Cmax and pooled AUC0–6 values, were greater for levofloxacin than moxifloxacin (Cmax: 1.43, 0.87 μg/ml, respectively, P=0.008; AUC0–6 6.1, 3.8 μg·min/ml, P<0.001 respectively). No treatment-emergent adverse events were reported.ConclusionSignificantly greater drug exposures were attained in aqueous humor following the administration of levofloxacin 1.5% than moxifloxacin 0.5% ophthalmic solution. Achieving considerable higher drug concentration in the aqueous humor with levofloxacin 1.5% may demonstrate a greater potential for bacterial eradication.

Does Critical Illness Change Levofloxacin Pharmacokinetics?

Levofloxacin is commonly used in critically ill patients for which existing data suggest nonstandard dosing regimens should be used. The objective of this study was to compare the population pharmacokinetics of levofloxacin in critically ill and in non-critically ill patients. Adult patients with a clinical indication for levofloxacin were eligible for participation in this prospective pharmacokinetic study. Patients were given 500 mg or 750 mg daily by intravenous administration with up to 11 blood samples taken on day 1 or 2 of therapy. Plasma samples were analyzed and population pharmacokinetic analysis was undertaken using Pmetrics. Thirty-five patients (18 critically ill) were included. The mean (standard deviation [SD]) age, weight, and Cockcroft-Gault creatinine clearance for the critically ill and for the non-critically ill patients were 60.3 (16.4) and 72.0 (11.6) years, 78.5 (14.8) and 70.9 (15.8) kg, and 71.9 (65.8) and 68.2 (30.1) ml/min, respectively. A two-compartment linear model best described the data. Increasing creatinine clearance was the only covariate associated with increasing drug clearance. The presence of critical illness did not significantly affect any pharmacokinetic parameter. The mean (SD) parameter estimates were as follows: clearance, 8.66 (3.85) liters/h; volume of the central compartment (Vc), 41.5 (24.5) liters; intercompartmental clearance constants from central to peripheral, 2.58 (3.51) liters/h; and peripheral to central compartments, 0.90 (0.58) liters/h. Monte Carlo dosing simulations demonstrated that achievement of therapeutic exposures was dependent on renal function, pathogen, and MIC. Critical illness appears to have no independent effect on levofloxacin pharmacokinetics that cannot be explained by altered renal function.

Identifying 24 h variation in the pharmacokinetics of levofloxacin: a population pharmacokinetic approach

The objective of this study was to investigate whether the pharmacokinetics of orally administered levofloxacin show 24h variation. Levofloxacin was used as a model compound for solubility and permeability independent absorption and passive renal elimination. In this single centre, crossover, open label study, 12 healthy subjects received an oral dose of 1000mg levofloxacin at six different time points equally divided over the 24h period. Population pharmacokinetic modelling was used to identify potential 24h variation in the pharmacokinetic parameters of this drug. The pharmacokinetics of levofloxacin could be described by a one compartment model with first order clearance and a transit compartment to describe drug absorption. The fit of the model was significantly improved when the absorption rate constant was described as a cosine function with a fixed period of 24h, a relative amplitude of 47% and a peak around 08.00h in the morning. Despite this variation in absorption rate constant, simulations of a once daily dosing regimen showed that tmax , Cmax and the area under the curve at steady-state were not affected by the time of drug administration. The finding that the absorption rate constant showed considerable 24h variation may be relevant for drugs with similar physicochemical properties as levofloxacin that have a narrower therapeutic index. Levofloxacin, however, can be dosed without taking into account the time of day, at least in terms of its pharmacokinetics.

HS-23, a standardized extract of the dried flower buds of Lonicera japonica, has no major impact on drug transporters and on the pharmacokinetics of ceftriaxone and levofloxacin in rats

Concurrent administration of herbal drugs that modulate drug transporter activities can cause herb–drug interactions in the process of the absorption, distribution, and elimination of drugs and thereby, modulate drug efficacy and toxicity. For this reason, regulatory agencies have instituted guidelines for the investigation of potential herb–drug interactions during the drug development process. Therefore, the purpose of this study was to investigate the herb–drug interaction potential of HS-23, an extract of the dried flower buds of Lonicera japonica, which is being evaluated for use in the treatment of sepsis in a phase II clinical study. The inhibitory effects of HS-23 on the transport functions of organic cation transporter (OCT)1, OCT2, organic anion transporter (OAT)1, OAT3, organic anion transporting polypeptide (OATP)1B1, OATP1B3, P-glycoprotein (P-gp), and breast cancer resistance protein (BCRP) were investigated in HEK293 and LLC-PK1 cells. The effects of HS-23 on the pharmacokinetics of ceftriaxone and levofloxacin, common combination drugs for sepsis treatment were also examined in rats. HS-23 (up to 100 μg/mL) did not inhibit the in vitro transport activities of OCT1/2, OAT1/3, OATP1B1/1B3, P-gp, and BCRP or the pharmacokinetics of ceftriaxone and levofloxacin in vivo after a single intravenous dose of 40 mg/kg. In conclusion, HS-23 may not have significant herb–drug interactions with the prevalently used ceftriaxone and levofloxacin, in rats even at its effective dose.

Pharmacokinetics and the optimal regimen for levofloxacin in critically ill patients receiving continuous hemodiafiltration.

The aim of this study was to establish the pharmacokinetics of levofloxacin (LVFX) and determine the optimal dose of this drug in critically ill patients receiving continuous hemodiafiltration (CHDF). The results of in vivo and in vitro studies showed the pharmacokinetics of LVFX total clearance (CLtotal) according to the creatinine clearance (CLCre), dialysate flow (QD), and ultrafiltrate flow (QF), to be as follows: CLtotal (l/h) = 0.0836 × CLCre (ml/min) + 0.013 × body weight (kg) + 0.94(QD + QF) (l/h). The optimal dose of LVFX was expressed by the following formula: 50 × CLtotal. These results demonstrate that the usual dose of LVFX (500 mg) was sufficient for the patients evaluated in this study.

The pharmacokinetic interaction between levofloxacin and sunitinib

BackgroundThe aim of this study was to evaluate the impact of sunitinib on pharmacokinetics of levofloxacin. The previous study proved that levofloxacin co-administered with sunitib changes the following pharmacokinetic parameters i.e. Cmax and AUC for both sunitinib and SU012662 (sunitinib metabolite). We will also investigate if the limited sample strategy can be applied for levofloxacin. MethodsRabbits were divided into two groups. In both groups there were six animals. In the control group levofloxacin was administered and in investigated group levofloxacin and sunitinib were co-administered. The dose of levofloxacin was 20mg/kg and the dose of sunitinib was 25mg. The concentration in plasma was determined by HPLC-FLD. The pharmacokinetic parameters were evaluated by WinNonLin software. The results were evaluated by the following statistical tests: Shapiro–Wilk, t-Student and Mann–Whitney test. ResultsPharmacokinetics of levofloxacin obeys the two-compartment model. Sunitinib influences the following pharmacokinetic parameters of levofloxacin: half-life, elimination constant and volume of distribution. Statistical analysis proved that there is a correlation between AUC and the following five time-points: 0.25h, 4h, 6h, 10h and 12h. ConclusionsThe study proved that there is a potential pharmacokinetic interaction between sunitinib and levofloxacin. The statistical analysis proved that the limited sample strategy can be applied for levofloxacin.

Personalized therapeutics for levofloxacin: a focus on pharmacokinetic concerns

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. 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.ConclusionPersonalized 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.

Pharmacokinetics of Ofloxacin and Levofloxacin for Prevention and Treatment of Multidrug-Resistant Tuberculosis in Children

Limited data on fluoroquinolone pharmacokinetics and cardiac effects in children exist. Among 22 children receiving drug-resistant tuberculosis prophylaxis or treatment, serum concentrations following oral doses of levofloxacin (15 mg/kg of body weight) and ofloxacin (20 mg/kg) were lower than those expected from existing pediatric data, possibly due to differences in the formulations (crushed tablets). Drug exposures were lower than those in adults following standard doses and below the proposed pharmacodynamic targets, likely due to more rapid elimination in children. No QT prolongation was observed.

Comparative Pharmacokinetics of Levofloxacin in Healthy and Renal Damaged Muscovy Ducks following Intravenous and Oral Administration

The pharmacokinetics aspects of levofloxacin were studied in healthy and experimentally renal damaged Muscovy ducks after single intravenous (IV) and oral (PO) dose of 10 mg kg−1 bwt. Following IV administration, elimination half-life (t 1/2(β)) and mean residence time (MRT) were longer in renal damaged ducks than in healthy ones. Total clearance (Cltot) in renal damaged ducks (0.20 L kg−1 h−1) was significantly lower as compared to that in healthy ones (0.41 L kg−1 h−1). Following PO administration, the peak serum concentration (C max) was higher in renal damaged than in healthy ducks and was achieved at maximum time (t max) of 2.47 and 2.05 h, respectively. The drug was eliminated (t 1/2(el)) at a significant slower rate (3.94 h) in renal damaged than in healthy ducks (2.89 h). The pharmacokinetic profile of levofloxacin is altered in renal damaged ducks due to the increased serum levofloxacin concentrations compared with that in clinically healthy ducks. Oral administration of levofloxacin at 10 mg kg−1 bwt may be highly efficacious against susceptible bacteria in ducks. Also, the dose of levofloxacin should be reduced in renal damaged ducks. Pharmacokinetic/pharmacodynamic integration revealed significantly higher values for C max/MIC and AUC/MIC ratios in renal damaged ducks than in healthy ones, indicating the excellent pharmacokinetic characteristics of levofloxacin in renal damaged ducks.