Accumulation of pefloxacin in the lower respiratory tract demonstrated by bronchoalveolar lavage

Panteix, G.; Harf, R; Jf, Desnottes; Gosselet, H; Leclercq, M.; Diallo, N.; Couprie, N; Desbos, Agnès; M, Perrin Fayolle; Ballereau, M

doi:10.1093/jac/33.5.979

Cited by 17 publications

(2 citation statements)

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“…Bronchoalveolar lavage (BAL) is used in both drug research and in clinical practice as a way to quantify drug concentrations from epithelial lining fluid (ELF) [ 6 , 10 ] and alveolar cells (AC) [ 6 , 11 ]. Information about the extent of distribution, often parameterized as ELF/plasma and AC/plasma concentration ratios, is of great value in order to assess whether sufficient drug concentrations are achieved at extracellular (ELF) and intracellular (AC) sites.…”

Section: Introductionmentioning

confidence: 99%

A pharmacometric pulmonary model predicting the extent and rate of distribution from plasma to epithelial lining fluid and alveolar cells—using rifampicin as an example

Clewe

Goutelle

Conte

et al. 2015

Eur J Clin Pharmacol

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PurposeThe purpose of the study was to develop a drug-unspecific approach to pharmacometric modeling for predicting the rate and extent of distribution from plasma to epithelial lining fluid (ELF) and alveolar cells (AC) for data emanating from studies involving bronchoalveolar lavage (BAL) sampling, using rifampicin (RIF) as an example.MethodsData consisting of RIF plasma concentrations sampled at approximately 2 and 4 h postdose and ELF and AC concentrations quantified from one BAL sample, taken at approximately 4 h postdose, in 40 adult subjects without tuberculosis was used as an example for model development.ResultsThis study emphasized the usage of drug-specific plasma pharmacokinetics (PK) for a correct characterization of plasma to pulmonary distribution. As such, RIF PK was described using absorption transit compartments and a one compartment distribution model coupled with an enzyme turn-over model. The ELF and AC distribution model consisted of characterization of the rate of distribution of drug from plasma to ELF and AC by two distribution rate constant, kELF and kAC, respectively. The extent of distribution to ELF and AC was described by unbound ELF/plasma concentration ratio (RELF/unbound-plasma) and unbound AC/plasma concentration ratio (RAC/unbound-plasma) which typical values were predicted to be 1.28 and 5.5, respectively.ConclusionsThe model together with a drug-specific plasma PK description provides a tool for handling data from both single and multiple BAL sampling designs and directly predicts the rate and extent of distribution from plasma to ELF and AC. The model can be further used to investigate design aspects of optimized BAL studies.

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Section: Introductionmentioning

confidence: 99%

A pharmacometric pulmonary model predicting the extent and rate of distribution from plasma to epithelial lining fluid and alveolar cells—using rifampicin as an example

Clewe

Goutelle

Conte

et al. 2015

Eur J Clin Pharmacol

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“…Bronchoalveolar lavage (BAL) is a semi-invasive method used in both research and clinical practice as a way of quantifying drug concentrations from epithelial lining fluid (ELF) and alveolar cells (AC) [ 1 – 5 ]. For pulmonary infections, concentrations of antibiotics in ELF for extracellular pathogens and alveolar macrophage (AM) cells for intracellular pathogens have for example been proposed to reflect antibiotic activity in pneumonia [ 4 ].…”

Section: Introductionmentioning

confidence: 99%

Evaluation of optimized bronchoalveolar lavage sampling designs for characterization of pulmonary drug distribution

Clewe

Karlsson

Simonsson

2015

J Pharmacokinet Pharmacodyn

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Bronchoalveolar lavage (BAL) is a pulmonary sampling technique for characterization of drug concentrations in epithelial lining fluid and alveolar cells. Two hypothetical drugs with different pulmonary distribution rates (fast and slow) were considered. An optimized BAL sampling design was generated assuming no previous information regarding the pulmonary distribution (rate and extent) and with a maximum of two samples per subject. Simulations were performed to evaluate the impact of the number of samples per subject (1 or 2) and the sample size on the relative bias and relative root mean square error of the parameter estimates (rate and extent of pulmonary distribution). The optimized BAL sampling design depends on a characterized plasma concentration time profile, a population plasma pharmacokinetic model, the limit of quantification (LOQ) of the BAL method and involves only two BAL sample time points, one early and one late. The early sample should be taken as early as possible, where concentrations in the BAL fluid ≥ LOQ. The second sample should be taken at a time point in the declining part of the plasma curve, where the plasma concentration is equivalent to the plasma concentration in the early sample. Using a previously described general pulmonary distribution model linked to a plasma population pharmacokinetic model, simulated data using the final BAL sampling design enabled characterization of both the rate and extent of pulmonary distribution. The optimized BAL sampling design enables characterization of both the rate and extent of the pulmonary distribution for both fast and slowly equilibrating drugs.Electronic supplementary materialThe online version of this article (doi:10.1007/s10928-015-9438-9) contains supplementary material, which is available to authorized users.

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Microdialysis in Lung Tissue: Monitoring of Exogenous and Endogenous Compounds

Feurstein

Zeitlinger

2011

Applications of Microdialysis in Pharmaceutical Science

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Accumulation of pefloxacin in the lower respiratory tract demonstrated by bronchoalveolar lavage

Cited by 17 publications

References 0 publications

A pharmacometric pulmonary model predicting the extent and rate of distribution from plasma to epithelial lining fluid and alveolar cells—using rifampicin as an example

A pharmacometric pulmonary model predicting the extent and rate of distribution from plasma to epithelial lining fluid and alveolar cells—using rifampicin as an example

Evaluation of optimized bronchoalveolar lavage sampling designs for characterization of pulmonary drug distribution

Microdialysis in Lung Tissue: Monitoring of Exogenous and Endogenous Compounds

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