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

Verfasser / Beitragende:
[Oskar Clewe, Mats Karlsson, Ulrika Simonsson]
Ort, Verlag, Jahr:
2015
Enthalten in:
Journal of Pharmacokinetics and Pharmacodynamics, 42/6(2015-12-01), 699-708
Format:
Artikel (online)
ID: 605533784
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024 7 0 |a 10.1007/s10928-015-9438-9  |2 doi 
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245 0 0 |a Evaluation of optimized bronchoalveolar lavage sampling designs for characterization of pulmonary drug distribution  |h [Elektronische Daten]  |c [Oskar Clewe, Mats Karlsson, Ulrika Simonsson] 
520 3 |a 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. 
540 |a The Author(s), 2015 
690 7 |a Bronchoalveolar lavage  |2 nationallicence 
690 7 |a Pulmonary distribution  |2 nationallicence 
690 7 |a Sampling design  |2 nationallicence 
690 7 |a Pharmacometrics  |2 nationallicence 
700 1 |a Clewe  |D Oskar  |u Department of Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden  |4 aut 
700 1 |a Karlsson  |D Mats  |u Department of Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden  |4 aut 
700 1 |a Simonsson  |D Ulrika  |u Department of Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden  |4 aut 
773 0 |t Journal of Pharmacokinetics and Pharmacodynamics  |d Springer US; http://www.springer-ny.com  |g 42/6(2015-12-01), 699-708  |x 1567-567X  |q 42:6<699  |1 2015  |2 42  |o 10928 
856 4 0 |u https://doi.org/10.1007/s10928-015-9438-9  |q text/html  |z Onlinezugriff via DOI 
898 |a BK010053  |b XK010053  |c XK010000 
900 7 |a Metadata rights reserved  |b Springer special CC-BY-NC licence  |2 nationallicence 
908 |D 1  |a research-article  |2 jats 
949 |B NATIONALLICENCE  |F NATIONALLICENCE  |b NL-springer 
950 |B NATIONALLICENCE  |P 856  |E 40  |u https://doi.org/10.1007/s10928-015-9438-9  |q text/html  |z Onlinezugriff via DOI 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Clewe  |D Oskar  |u Department of Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Karlsson  |D Mats  |u Department of Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Simonsson  |D Ulrika  |u Department of Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden  |4 aut 
950 |B NATIONALLICENCE  |P 773  |E 0-  |t Journal of Pharmacokinetics and Pharmacodynamics  |d Springer US; http://www.springer-ny.com  |g 42/6(2015-12-01), 699-708  |x 1567-567X  |q 42:6<699  |1 2015  |2 42  |o 10928