Single- and Multiple-dose Pharmacokinetics of Oral Moxifloxacin and Clarithromycin, and Concentrations in Serum, Saliva and Faeces

Burkhardt, Olaf; Börner, K.; Staß, Heino; Beyer, Gerrit; Allewelt, M.; Nord, Carl Erik; Lode, H.

doi:10.1080/0036554021000026963

Cited by 42 publications

(32 citation statements)

References 17 publications

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“…Data of four previous publications about the plasma concentrations of the 14-hydroxy metabolite in humans are largely in agreement, with an overall ratio of the AUC metabolite to the AUC parent compound of 34.9 Ϯ 2.1% (4,7,8,18). Interstitial concentrations of the more hydrophilic 14-hydroxy metabolite are unknown at present.…”

Section: Discussionsupporting

confidence: 67%

Pharmacokinetics of Single- and Multiple-Dose Oral Clarithromycin in Soft Tissues Determined by Microdialysis

Traunmüller

Zeitlinger

Zeleny

et al. 2007

Antimicrob Agents Chemother

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Clarithromycin, a 14-membered ring macrolide, is antimicrobially active against a broad range of gram-positive and certain gram-negative pathogens frequently isolated from softtissue infections and bite wounds (11). Clarithromycin is considered a therapeutic alternative in special cases of minor softtissue infections and penicillin allergy or in cases of nontuberculous mycobacterial skin infections (19,20). High tissue concentrations of the class of the macrolides have been reported previously in the literature (10,13,21). Indeed, intracellular accumulation of macrolides in isolated peripheral blood phagocytes, alveolar macrophages, and tissue culture cells of human origin has been demonstrated previously (9, 16). To date, investigations of in vivo tissue pharmacokinetics (PK) of clarithromycin have been confined to concentrations derived from homogenized biopsy samples of the upper and lower respiratory tract and epithelial lining fluid collection obtained by bronchoalveolar lavage (10, 13, 21). The results derived from homogenized biopsy samples, as frequently used in previous studies, represent an average concentration of all tissue components extracted, including blood cells, intracellular fluid, interstitial fluid, and structural tissue components, and may therefore cause confusion with regard to the actual concentration of an antimicrobial agent in a defined compartment. These data, thus, provide only limited insight into the time course of concentration at the relevant site of most bacterial infections, namely, the extracellular-space fluid. Hence, we used the microdialysis technique, which is capable of the continuous assessment of unbound, i.e., microbiologically active concentrations of clarithromycin in the interstitial-space fluid of soft tissues (15).Knowledge about the concentration-time profiles of free clarithromycin in the interstitial-space fluid of soft tissues can be considered a prerequisite for dosage recommendations in the treatment of extracellularly proliferating bacteria causing soft-tissue infections. Hence, the aim of the present study was to determine free interstitial concentrations of clarithromycin in subcutaneous adipose tissue and skeletal muscle after oral single-and multiple-dose administration to healthy male volunteers. MATERIALS AND METHODSThe study took place at the Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria. The study protocol was approved by the local Ethics Committee, and the study was performed in accordance with the Declaration of Helsinki 1964 (including current revisions), the Austrian Drug Law, and the Good Clinical Practice Guidelines.Healthy volunteers. Seven healthy male volunteers between the ages of 25 and 37 years were enrolled into the study. Written informed consent was obtained from each volunteer prior to any study-related investigation or intervention. Each volunteer underwent a screening examination consisting of the following: medical history, physical examination, routine laboratory tests, heart rate, blood pres...

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Section: Discussionsupporting

confidence: 67%

Pharmacokinetics of Single- and Multiple-Dose Oral Clarithromycin in Soft Tissues Determined by Microdialysis

Traunmüller

Zeitlinger

Zeleny

et al. 2007

Antimicrob Agents Chemother

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“…To date, there has been no comparison in the literature of the analysis of clarithromycin and linezolid concentrations in serum and in oral fluid of patients with MDR-TB. However, there are several studies describing pharmacokinetics of clarithromycin and OH-clarithromycin in saliva (15,16) but none describing pharmacokinetics of linezolid in oral fluid. Clarithromycin administered to 12 healthy volunteers in a dose of 500 mg twice daily resulted in an AUC 0 -12 of 18.0 Ϯ 5.0 mg · h/liter (15).…”

Section: Discussionmentioning

confidence: 99%

“…However, there are several studies describing pharmacokinetics of clarithromycin and OH-clarithromycin in saliva (15,16) but none describing pharmacokinetics of linezolid in oral fluid. Clarithromycin administered to 12 healthy volunteers in a dose of 500 mg twice daily resulted in an AUC 0 -12 of 18.0 Ϯ 5.0 mg · h/liter (15). We observed a similar AUC 0 -12 of 15.7 mg · h/liter for the one patient that was administered 500 mg clarithromycin.…”

Section: Discussionmentioning

confidence: 99%

“…Saliva/serum ratios of around 2 were reported, lower than the ratio of 3 observed in our study. However, no data were presented comparing results from the analysis of clarithromycin concentrations in serum and in oral fluid, since that study aimed to describe kinetics and not to clinically validate the analysis of oral fluid (15). Another study described pharmacokinetics of clarithromycin in saliva and serum after a single dose of 500 mg clarithromycin (16).…”

Section: Discussionmentioning

confidence: 99%

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Clinical Validation of the Analysis of Linezolid and Clarithromycin in Oral Fluid of Patients with Multidrug-Resistant Tuberculosis

Bolhuis

Altena

Hateren

et al. 2013

Antimicrob Agents Chemother

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dLinezolid plays an increasingly important role in the treatment of multidrug-resistant tuberculosis (MDR-TB). However, patients should be carefully monitored due to time-and dose-dependent toxicity. Clarithromycin plays a more modest role. Therapeutic drug monitoring may contribute to assessment of treatment regimens, helping to reduce toxicity while maintaining adequate drug exposure. Oral fluid sampling could provide a welcome alternative in cases where conventional plasma sampling is not possible or desirable. The aim of this study was to clinically validate the analysis of linezolid and clarithromycin and its metabolite hydroxyclarithromycin in oral fluid of patients with multidrug-resistant tuberculosis. Serum and oral fluid samples were simultaneously obtained and analyzed by using validated methods, after extensive cross-validation between the two matrices. Passing-Bablok regressions and Bland-Altman analysis showed that oral fluid analysis of linezolid and clarithromycin appeared to be suitable for therapeutic drug monitoring in MDR-TB patients. No correction factor is needed for the interpretation of linezolid oral fluid concentrations with a ratio of the linezolid concentration in serum to that in oral fluid of 0.97 (95% confidence interval [CI], 0.92 to 1.02). However, the clarithromycin concentration serum/clarithromycin concentration in oral fluid ratio is 3.07 (95% CI, 2.45 to 3.69). Analysis of hydroxyclarithromycin in oral fluid was not possible in this study due to a nonlinear relationship between the concentration in serum and that in oral fluid. In conclusion, the analysis of linezolid (no correction factor) and clarithromycin (correction factor of 3) in oral fluid is applicable for therapeutic drug monitoring in cases of multidrug-resistant tuberculosis as an alternative to conventional serum sampling. Easy sampling using a noninvasive technique may facilitate therapeutic drug monitoring for specific patient categories. T uberculosis (TB) is a mostly curable and preventable infectious disease caused by Mycobacterium tuberculosis. Approximately 3.7% of new tuberculosis patients and 20% of previously treated patients are infected with multidrug-resistant strains that are resistant to at least rifampin and isoniazid (1). Treatment regimens of multidrug-resistant tuberculosis (MDR-TB) should consist of at least four anti-TB drugs to which the bacterium is susceptible (2).The oxazolidinone linezolid is effective against M. tuberculosis and is increasingly used as a part of treatment regimens in patients with multidrug-resistant or extensively drug-resistant tuberculosis (3). However, patients should be carefully monitored due to the time-and dose-dependent serious toxicity of linezolid, such as myelosuppression and polyneuropathy (4).Clarithromycin has a less pronounced place in MDR-TB treatment regimens due to serum concentrations that usually do not reach MICs (5). Nevertheless, sufficiently high local clarithromycin concentrations are reached in epithelial lining fluid and alveolar cells (6, 7...

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“…A significantly higher ciprofloxacin AUC 0-∞ has been observed in Nigerian and Chinese compared with German subjects as well when administered intravenously (139,141,142). Interethnic PK differences have not been described for levofloxacin, gatifloxacin and moxifloxacin (161,(283)(284)(285)(286)(287).…”

Section: Fluoroquinolones -Ciprofloxacin Is Moderately Lipophilic Andmentioning

confidence: 99%

Improving antibiotic dosing in critically ill Australian Indigenous patients with severe sepsis

Tsai¹

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Sepsis is a major health issue in the Australian Indigenous population. Unfortunately, the high rates of mortality and morbidity caused by sepsis or severe sepsis in this population have not significantly reduced over recent decades. Research into the role of optimisation of antibiotic therapy for improving patient outcomes is certainly an important area of need. In other patient populations, there is increasing evidence of an improvement of clinical cure rates and survival in patients with severe sepsis when antibiotic dosing results in therapeutic concentrations, that is, achieves pharmacokinetic/pharmacodynamic (PK/PD) targets. However, numerous PK changes caused by the altered physiology associated with critical illness may reduce the likelihood of such effective dosing.Previous studies have identified a number of physiological characteristics in the Australian Indigenous population which suggest that interethnic PK differences are likely in comparison with the non-Indigenous. As most PK data of antibiotics were obtained from healthy Caucasian volunteers, whether these data can be extrapolated to the critically ill Indigenous patients requires investigation.The aims of this thesis are to describe the PK of meropenem, ceftriaxone, vancomycin and piperacillin in severely septic Indigenous patients; compare the PK with existing data from nonIndigenous patients; design optimised dosing regimens for each of the study antibiotics; and quantify the variation in renal function of critically ill Indigenous patients. This thesis consists of nine Chapters:Chapter one provides an overview of the current clinical challenges encountered in antibiotic dosing in critically ill patients. It also discusses specific physiological characteristics of Australian Indigenous patients which may lead to different PK compared with non-Indigenous comparators.Chapter two comprises of a narrative review which discusses the PK/PD factors that should be considered when prescribing antibiotics to critically ill patients. This Chapter summarises data which describe an improvement in clinical outcome when antibiotics achieve PK/PD targets. ThisChapter concludes to support an individualised approach to dosing antibiotics as opposed to the 'one dose fits all' approach that is common to clinical practice.ii Chapter three incorporates a systematic review which investigates the published data describing differences in antibiotic PK between different ethnic groups. No reports on PK in Indigenous Australians were found. The predominant data described differences in PK between the Asian and Caucasian ethnicities. Typically, Asian subjects manifested higher antibiotic concentrations for antibiotics that have significant hepatic metabolism, are substrates to p-glycoprotein or other forms of active transport and/or have high alpha-1-acid glycoprotein binding.Chapter four incorporates a study which described the renal function of critically ill Australian Indigenous patients. This study found a numerically higher incidence of augmented renal clea...

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Single- and Multiple-dose Pharmacokinetics of Oral Moxifloxacin and Clarithromycin, and Concentrations in Serum, Saliva and Faeces

Cited by 42 publications

References 17 publications

Pharmacokinetics of Single- and Multiple-Dose Oral Clarithromycin in Soft Tissues Determined by Microdialysis

Pharmacokinetics of Single- and Multiple-Dose Oral Clarithromycin in Soft Tissues Determined by Microdialysis

Clinical Validation of the Analysis of Linezolid and Clarithromycin in Oral Fluid of Patients with Multidrug-Resistant Tuberculosis

Improving antibiotic dosing in critically ill Australian Indigenous patients with severe sepsis

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