caa a22 4500 605533784 CHVBK 20210128100839.0 cr unu---uuuuu 210128e20151201xx s 000 0 eng 10.1007/s10928-015-9438-9 doi (NATIONALLICENCE)springer-10.1007/s10928-015-9438-9 Evaluation of optimized bronchoalveolar lavage sampling designs for characterization of pulmonary drug distribution [Elektronische Daten] [Oskar Clewe, Mats Karlsson, Ulrika Simonsson] 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. The Author(s), 2015 Bronchoalveolar lavage nationallicence Pulmonary distribution nationallicence Sampling design nationallicence Pharmacometrics nationallicence Clewe Oskar Department of Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden aut Karlsson Mats Department of Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden aut Simonsson Ulrika Department of Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden aut Journal of Pharmacokinetics and Pharmacodynamics Springer US; http://www.springer-ny.com 42/6(2015-12-01), 699-708 1567-567X 42:6<699 2015 42 10928 https://doi.org/10.1007/s10928-015-9438-9 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s10928-015-9438-9 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Clewe Oskar Department of Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden aut NATIONALLICENCE 700 1- Karlsson Mats Department of Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden aut NATIONALLICENCE 700 1- Simonsson Ulrika Department of Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden aut NATIONALLICENCE 773 0- Journal of Pharmacokinetics and Pharmacodynamics Springer US; http://www.springer-ny.com 42/6(2015-12-01), 699-708 1567-567X 42:6<699 2015 42 10928