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

ABSTRACT: 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.

SUBMITTER: Clewe O

PROVIDER: S-EPMC4624821 | biostudies-literature | 2015 Dec

REPOSITORIES: biostudies-literature

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

Clewe Oskar O Karlsson Mats O MO Simonsson Ulrika S H US

Journal of pharmacokinetics and pharmacodynamics 20150828 6

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 ...[more]

PMID: 26316105

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Project description:BackgroundThe provision of guidance in ventilator therapy by continuous monitoring of regional lung ventilation, aeration and respiratory system mechanics is the main clinical benefit of electrical impedance tomography (EIT). A new application was recently described in critically ill patients undergoing diagnostic bronchoalveolar lavage (BAL) with the intention of using EIT to identify the region where sampling was performed. Increased electrical bioimpedance was reported after fluid instillation. To verify the accuracy of these findings, contradicting the current EIT knowledge, we have systematically analysed chest EIT data acquired under controlled experimental conditions in animals undergoing a large number of BAL procedures.MethodsOne hundred thirteen BAL procedures were performed in 13 newborn piglets positioned both supine and prone. EIT data was obtained at 13 images before, during and after each BAL. The data was analysed at three time points: (1) after disconnection from the ventilator before the fluid instillation and by the ends of fluid (2) instillation and (3) recovery by suction and compared with the baseline measurements before the procedure. Functional EIT images were generated, and changes in pixel electrical bioimpedance were calculated relative to baseline. The data was examined in the whole image and in three (ventral, middle, dorsal) regions-of-interest per lung.ResultsCompared with the baseline phase, chest electrical bioimpedance fell after the disconnection from the ventilator in all animals in both postures during all procedures. The fluid instillation further decreased electrical bioimpedance. During fluid recovery, electrical bioimpedance increased, but not to baseline values. All effects were highly significant (p <?0.001). The fractional changes in individual regions-of-interest were posture-dependent. The regional fall in electrical bioimpedance was smaller in the ventral and larger in the dorsal regions after the fluid instillation than after the initial disconnection to ambient pressure in supine animals (p <?0.001) whereas these changes were of comparable amplitude in prone position.ConclusionsThe results of this study show a regionally dissimilar initial fall in electrical bioimpedance caused by non-uniform aeration loss at the beginning of the BAL procedure. They also confirm a further pronounced fall in bioimpedance during fluid instillation, incomplete recovery after suction and a posture-dependent distribution pattern of these effects.

Dataset Information

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

Publications

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

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