Pharmacokinetic Evaluation of Oral Levofloxacin in Human Immunodeficiency Virus-Infected Subjects Receiving Concomitant Antiretroviral Therapy

Villani, Paola; Viale, Pierluigi; Signorini, Liana; Cadeo, Barbara; Marchetti, Federico; Villani, Alberto; Fiocchi, Claudio; Regazzi, Mario; Carosi, Giampiero

doi:10.1128/aac.45.7.2160-2162.2001

Cited by 14 publications

(3 citation statements)

References 14 publications

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“…increase in levofloxacin concentrations when levofloxacin was given to HIV-infected patients treated with efavirenz or nelfinavir, but that study had no HIV-infected control group, and the comparison was instead made with historical data (24). The lack of an effect of the drug administration method on the overall bioavailability of levofloxacin is reassuring, given the limited availability of child-friendly levofloxacin formulations and the frequent need to crush levofloxacin tablets intended for use by adults for administration to young children.…”

Section: Discussionmentioning

confidence: 99%

Levofloxacin Population Pharmacokinetics in South African Children Treated for Multidrug-Resistant Tuberculosis

Denti

Garcia-Prats

Draper

et al. 2018

Antimicrob Agents Chemother

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Levofloxacin is increasingly used in the treatment of multidrug-resistant tuberculosis (MDR-TB). There are limited pediatric pharmacokinetic data to inform dose selection for children. Children routinely receiving levofloxacin (250-mg adult tablets) for MDR-TB prophylaxis or disease in Cape Town, South Africa, underwent pharmacokinetic sampling following receipt of a dose of 15 or 20 mg/kg of body weight given as a whole or crushed tablet(s) orally or via a nasogastric tube. Pharmacokinetic parameters were estimated using nonlinear mixed-effects modeling. Model-based simulations were performed to estimate the doses across weight bands that would achieve adult exposures with 750-mg once-daily dosing. One hundred nine children were included. The median age was 2.1 years (range, 0.3 to 8.7 years), and the median weight was 12 kg (range, 6 to 22 kg). Levofloxacin followed 2-compartment kinetics with first-order elimination and absorption with a lag time. After inclusion of allometric scaling, the model characterized the age-driven maturation of clearance (CL), with the effect reaching 50% of that at maturity at about 2 months after birth and 100% of that at maturity by 2 years of age. CL in a typical child (weight, 12 kg; age, 2 years) was 4.7 liters/h. HIV infection reduced CL by 16%. By use of the adult 250-mg formulation, levofloxacin exposures were substantially lower than those reported in adults receiving a similar dose on a milligram-per-kilogram basis. To achieve adult-equivalent exposures at a 750-mg daily dose, higher levofloxacin pediatric doses of from 18 mg/kg/day for younger children with weights of 3 to 4 kg (due to immature clearance) to 40 mg/kg/day for older children may be required. The doses of levofloxacin currently recommended for the treatment of MDR-TB in children result in exposures considerably lower than those in adults. The effects of different formulations and formulation manipulation require further investigation. We recommend age- and weight-banded doses of 250-mg tablets of the adult formulation most likely to achieve target concentrations for prospective evaluation.

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Section: Discussionmentioning

confidence: 99%

Levofloxacin Population Pharmacokinetics in South African Children Treated for Multidrug-Resistant Tuberculosis

Denti

Garcia-Prats

Draper

et al. 2018

Antimicrob Agents Chemother

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“…For example, the Tmax of levofloxacin was prolonged by 50% following efavirenz concurrent administration and this was ascribed to up-regulation of Pglycoprotein induced by efavirenz. 17 Moreover, in our previous study, the Tmax of proguanil was prolonged significantly following efavirenz concurrent administration and this was ascribed to up-regulation of P-glycoprotein induced by efavirenz. 8 The total systemic exposure (AUCT) of amodiaquine A B Fig.…”

Section: Discussionmentioning

confidence: 98%

Effects of concurrent administration of efavirenz on the disposition kinetics of amodiaquine in healthy volunteers

Soyinka

Onyeji

Nathaniel

et al. 2013

Journal of Pharmacy Research

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“…Levofloxacin does not alter the pharmacokinetics of zidovudine, efavirenz, or nelfinavir, and ciprofloxacin does not alter the pharmacokinetics of didanosine [33,292,293]. Note that there is an absorption interaction between ciprofloxacin and didanosine with cations as discussed previously [33,34].…”

Section: Metabolism Interactionsmentioning

confidence: 89%

Quinolones

Guay¹

2011

Drug Interactions in Infectious Diseases

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Fluoroquinolone (FQ) antimicrobials are among the most commonly used agents in the outpatient and institutional patient care environments. Due to this high frequency of utilization, the potential for deleterious drug-drug interactions with nonantimicrobials is also high. The majority of interactions with the FQs involve deleterious effects on the FQ component. These are also the most clinically-important interactions with these agents. Multivalent cations such as Mg , and other minerals as well as drugs such as sucralfate, lanthanum, sevelamer, and didanosine (the cation-supplemented version of the latter) can substantially reduce FQ bioavailability, leading the subtherapeutic drug concentrations at the infection site and clinical failure. Separation of dose administrations may or may not reduce the magnitude of these interactions. Ciprofloxacin, norfloxacin, and two experimental FQs in clinical trials (pazufloxacin and prulifloxacin) act as moderate cytochrome P450 enzyme inhibitors and may increase serum concentrations of theophylline and caffeine. Warfarin pharmacodynamics are variably affected by the FQs. The pharmacodynamic interactions between NSAIDs and FQs are only relevant if fenbufen is used concurrently with enoxacin or, possibly, prulifloxacin. Caution is warranted if sparfloxacin or moxifloxacin is used concurrently with other medications prolonging the QTc interval or if patients have other risk factors for prolongation of the QTc interval (e.g. abnormal QTc interval pre-treatment, electrolyte abnormalities, use of starvation-liquid diets, or history of heart disease). Fluoroquinolone antimicrobials can be used effectively and safely in the vast majority of patients if the clinician remembers those few drug-drug interactions that are clinically-important.

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Pharmacokinetic Evaluation of Oral Levofloxacin in Human Immunodeficiency Virus-Infected Subjects Receiving Concomitant Antiretroviral Therapy

Cited by 14 publications

References 14 publications

Levofloxacin Population Pharmacokinetics in South African Children Treated for Multidrug-Resistant Tuberculosis

Levofloxacin Population Pharmacokinetics in South African Children Treated for Multidrug-Resistant Tuberculosis

Effects of concurrent administration of efavirenz on the disposition kinetics of amodiaquine in healthy volunteers

Quinolones

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