caa a22 4500 477125956 CHVBK 20180405111649.0 cr unu---uuuuu 170330e19970901xx s 000 0 eng 10.1023/A:1012134219095 doi (NATIONALLICENCE)springer-10.1023/A:1012134219095 Human Intestinal Permeability of Piroxicam, Propranolol, Phenylalanine, and PEG 400 Determined by Jejunal Perfusion [Elektronische Daten] [Narushi Takamatsu, Lynda Welage, Nasir Idkaidek, Dong-Yue Liu, Peter Lee, Yayoi Hayashi, Julie Rhie, Hans Lennernäs, Jeffrey Barnett, Vinod Shah, Lawrence Lesko, Gordon Amidon] Purpose. To determine the human jejunal permeabilities of compounds utilizing different transport mechanisms using a regional perfusion approach and to establish a standard procedure for determining drug permeability class to be used for the establishment of drug product bioequivalence standards. Methods. Six healthy male volunteers participated in this study. A multi-lumen perfusion tube was inserted orally and positioned in the proximal region of the jejunum. A solution containing piroxicam, phenylalanine, propranolol, PEG 400 and PEG 4000 was perfused through the intestinal segment at a rate of 3.0 ml/min. Perfusate samples were quantitatively collected every 10 minutes for two 100 minute periods with an intermediate wash out period to determine intra and intersubject variation. Results. The mean Peff (±SD) of piroxicam, phenylalanine, propranolol, and PEG 400 were 10.40 ± 5.93, 6.67 ± 3.42, 3.59 ± 1.60, 0.80 ± 0.46 × 10−4 cm/sec, respectively. The coefficient of variation for the intersubject variability, first and second perfusion periods were: piroxicam, 60.5% and 57.1%; phenylalanine, 52.8% and 57.8%: propranolol, 62.1 % and 44.6%; and PEG 400, 81.7% and 42.3%, indicating a slightly lower CV for the second perfusion period in the same subject. The intrasubject CV's between the two perfusion periods were: 19.4%, 21.3%, 23.6% and 41.0% respectively, indicating a smaller intraindividual variation for all compounds studied. Conclusions. Piroxicam, a nonpolar drug exhibited the highest permeability of the compounds studied. The intrasubject CV was lower than the intersubject CV, indicating consistent permeability estimation within subjects. The methodology is useful for permeability estimation regardless of absorption mechanism and can be used to establish a consistent data base of human permeabilities for estimation of human drug absorption and for establishing the biopharmaceutic permeability class of drugs. Plenum Publishing Corporation, 1997 intestinal permeability nationallicence drug absorption nationallicence piroxicam nationallicence propranolol nationallicence biopharmaceutic classification scheme nationallicence Takamatsu Narushi Yamanouchi Pharmaceutical Co. Ltd., Shizuoka, Japan aut Welage Lynda College of Pharmacy, The University of Michigan, Ann Arbor, Michigan aut Idkaidek Nasir Faculty of Pharmacy, Jordan University of Science and Technology, Irbid, Jordan aut Liu Dong-Yue Biopharmaceutical Computing Center, Beijing Medical University, Beijing, China aut Lee Peter Janssen Research Foundation, Titusville, New Jersey aut Hayashi Yayoi Nagoya City University, Nagoya, Japan aut Rhie Julie FDA/CBER, 1401 Rockville Pike (HFM-515), 20852-1448, Rockville, Maryland aut Lennernäs Hans School of Pharmacy, Uppsala University, Uppsala, Sweden aut Barnett Jeffrey Department of Internal Medicine, Division of Gastroenterology University of Michigan Medical Center, Ann Arbor, Michigan aut Shah Vinod Food and Drug Administration, 20857, Rockville, Maryland aut Lesko Lawrence Food and Drug Administration, 20857, Rockville, Maryland aut Amidon Gordon College of Pharmacy, The University of Michigan, Ann Arbor, Michigan aut Pharmaceutical Research Kluwer Academic Publishers-Plenum Publishers 14/9(1997-09-01), 1127-1132 0724-8741 14:9<1127 1997 14 11095 https://doi.org/10.1023/A:1012134219095 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1023/A:1012134219095 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Takamatsu Narushi Yamanouchi Pharmaceutical Co. Ltd., Shizuoka, Japan aut NATIONALLICENCE 700 1- Welage Lynda College of Pharmacy, The University of Michigan, Ann Arbor, Michigan aut NATIONALLICENCE 700 1- Idkaidek Nasir Faculty of Pharmacy, Jordan University of Science and Technology, Irbid, Jordan aut NATIONALLICENCE 700 1- Liu Dong-Yue Biopharmaceutical Computing Center, Beijing Medical University, Beijing, China aut NATIONALLICENCE 700 1- Lee Peter Janssen Research Foundation, Titusville, New Jersey aut NATIONALLICENCE 700 1- Hayashi Yayoi Nagoya City University, Nagoya, Japan aut NATIONALLICENCE 700 1- Rhie Julie FDA/CBER, 1401 Rockville Pike (HFM-515), 20852-1448, Rockville, Maryland aut NATIONALLICENCE 700 1- Lennernäs Hans School of Pharmacy, Uppsala University, Uppsala, Sweden aut NATIONALLICENCE 700 1- Barnett Jeffrey Department of Internal Medicine, Division of Gastroenterology University of Michigan Medical Center, Ann Arbor, Michigan aut NATIONALLICENCE 700 1- Shah Vinod Food and Drug Administration, 20857, Rockville, Maryland aut NATIONALLICENCE 700 1- Lesko Lawrence Food and Drug Administration, 20857, Rockville, Maryland aut NATIONALLICENCE 700 1- Amidon Gordon College of Pharmacy, The University of Michigan, Ann Arbor, Michigan aut NATIONALLICENCE 773 0- Pharmaceutical Research Kluwer Academic Publishers-Plenum Publishers 14/9(1997-09-01), 1127-1132 0724-8741 14:9<1127 1997 14 11095 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer