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Enantiospecific disposition of pranoprofen in beagle dogs and rats
Author(s) -
Imai Teruko,
Nomura Tadayuki,
Aso Mayumi,
Otagiri Masaki
Publication year - 2003
Publication title -
chirality
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.43
H-Index - 77
eISSN - 1520-636X
pISSN - 0899-0042
DOI - 10.1002/chir.10207
Subject(s) - beagle , chemistry , enantiomer , pharmacokinetics , urine , bioavailability , oral administration , pharmacology , chirality (physics) , metabolism , glucuronide , stereochemistry , medicine , biochemistry , nambu–jona lasinio model , chiral symmetry breaking , physics , quantum mechanics , quark
The pharmacokinetic characteristics of pranoprofen enantiomer were examined and compared with the disposition of the corresponding isomer after the administration of racemic pranoprofen to beagle dogs and rats. The plasma levels of (+)‐(S)‐isomer were significantly higher than those of (–)‐(R)‐isomer in dogs and rats by either intravenous or oral administration. Although the oral bioavailability and absorption rate constant between the (–)‐(R)‐ and (+)‐(S)‐form was the same, the elimination rate constant of the (+)‐(S)‐form was significantly lower than that of the (–)‐(R)‐form in both dogs and rats. This discrepancy can be explained on the basis of differences in protein binding and the metabolism of the two enantiomers. The (–)‐(R)‐isomer was predominantly conjugated depending on its higher free plasma level and its faster metabolic rate than the (+)‐(S)‐form, and thus was excreted more rapidly in the urine and bile in the form of pranoprofen glucuronide. Furthermore, a (–)‐(R)‐ to (+)‐(S)‐inversion occurred to the extent of 14% in beagle dogs, but not in rats. This chiral inversion might be an important factor in the slow elimination of the (+)‐(S)‐form in dogs. The most efficient organ for chiral inversion was the liver, followed by kidney and intestine. Chirality 15:312–317, 2003. © 2003 Wiley‐Liss, Inc.