Stereoselective, competitive, and nonlinear plasma protein binding of ibuprofen enantiomers as determined in vivo in healthy subjects
dc.contributor.author | Dunn-Kucharski, Valerie A. | en_US |
dc.contributor.author | Cox, Steven R. | en_US |
dc.contributor.author | Paliwal, Jyoti K. | en_US |
dc.contributor.author | Smith, David E. | en_US |
dc.contributor.author | Berardi, Rosemary R. | en_US |
dc.contributor.author | Elta, Grace H. | en_US |
dc.date.accessioned | 2006-09-11T15:36:39Z | |
dc.date.available | 2006-09-11T15:36:39Z | |
dc.date.issued | 1993-04 | en_US |
dc.identifier.citation | Paliwal, Jyoti K.; Smith, David E.; Cox, Steven R.; Berardi, Rosemary R.; Dunn-Kucharski, Valerie A.; Elta, Grace H.; (1993). "Stereoselective, competitive, and nonlinear plasma protein binding of ibuprofen enantiomers as determined in vivo in healthy subjects." Journal of Pharmacokinetics and Biopharmaceutics 21(2): 145-161. <http://hdl.handle.net/2027.42/45048> | en_US |
dc.identifier.issn | 0090-466X | en_US |
dc.identifier.issn | 1573-8744 | en_US |
dc.identifier.uri | https://hdl.handle.net/2027.42/45048 | |
dc.identifier.uri | http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=retrieve&db=pubmed&list_uids=8229677&dopt=citation | en_US |
dc.description.abstract | The plasma protein binding and competitive inhibition parameters of R(−)- and S(+)-ibuprofen were determined in vivo in 12 healthy subjects. Subjects participated in a 4×4 Latin square design in which oral solutions of drug were administered as 300 mg R (−)-ibuprofen, 300 mg S (+)-ibuprofen, 300 mg R (−)-+300 mg S (+)-ibuprofen, and 300 mg R(−)-+600 mg S (+)-ibuprofen. Unlabeled ibuprofen enantiomers were quantitated using a stereospecific reversed-phase HPLC assay, and plasma protein binding experiments were performed using radiolabeled 14 C-enantiomers and an ultrafiltration method at 37C. At therapeutic drug concentrations, the protein binding of each enantiomer was greater than 99%. Furthermore, the binding of ibuprofen enantiomers was Stereoselective and mutually competitive, as well as nonlinear. The bound-free data were fitted to a model in which the non-linearity of plasma protein binding and competition between enantiomers for binding sites could be accommodated. There were substantial differences in the affinity of ibuprofen enantiomers for protein binding sites (RP2=0.358±0.185 vs. SP2=0.979 ±0.501 μg/ml; X±SD) but no differences in their binding capacity (RP1=160±86 vs. SP1=161 ±63 μg/ml). Although statistically significant, the differences in competitive inhibition parameters were more modest (SKI=0.661 ±0.363 vs. RKI=0.436 ±0.210 μg/ml). As a result, the intrinsic binding (i.e.), P1/P2J of R(−)-ibuprofen was greater than S(±)-ibuprofen, and the unbound fraction was significantly greater for S-enantiomer vs. R-enantiomer after a given dose of R-ibuprofen or racemate. | en_US |
dc.format.extent | 894690 bytes | |
dc.format.extent | 3115 bytes | |
dc.format.mimetype | application/pdf | |
dc.format.mimetype | text/plain | |
dc.language.iso | en_US | |
dc.publisher | Kluwer Academic Publishers-Plenum Publishers; Plenum Publishing Corporation ; Springer Science+Business Media | en_US |
dc.subject.other | Ibuprofen Enantiomers | en_US |
dc.subject.other | Stereoselectivity | en_US |
dc.subject.other | Biochemistry, General | en_US |
dc.subject.other | Pharmacy | en_US |
dc.subject.other | Nonlinearity | en_US |
dc.subject.other | Biomedicine | en_US |
dc.subject.other | Pharmacology/Toxicology | en_US |
dc.subject.other | Veterinary Medicine | en_US |
dc.subject.other | Biomedical Engineering | en_US |
dc.subject.other | Plasma Protein Binding | en_US |
dc.subject.other | Competitive Inhibition | en_US |
dc.subject.other | Ultrafiltration | en_US |
dc.title | Stereoselective, competitive, and nonlinear plasma protein binding of ibuprofen enantiomers as determined in vivo in healthy subjects | en_US |
dc.type | Article | en_US |
dc.subject.hlbsecondlevel | Pharmacy and Pharmacology | en_US |
dc.subject.hlbtoplevel | Health Sciences | en_US |
dc.description.peerreviewed | Peer Reviewed | en_US |
dc.contributor.affiliationum | College of Pharmacy, The University of Michigan, 48109-1065, Ann Arbor, Michigan; Upjohn Center for Clinical Pharmacology, Medical School, The University of Michigan, Ann Arbor, Michigan | en_US |
dc.contributor.affiliationum | College of Pharmacy, The University of Michigan, 48109-1065, Ann Arbor, Michigan; Upjohn Center for Clinical Pharmacology, Medical School, The University of Michigan, Ann Arbor, Michigan | en_US |
dc.contributor.affiliationum | College of Pharmacy, The University of Michigan, 48109-1065, Ann Arbor, Michigan | en_US |
dc.contributor.affiliationum | College of Pharmacy, The University of Michigan, 48109-1065, Ann Arbor, Michigan | en_US |
dc.contributor.affiliationum | Department of Internal Medicine, Medical School, The University of Michigan, Ann Arbor, Michigan | en_US |
dc.contributor.affiliationother | Clinical Pharmacokinetics Research Unit, The Upjohn Company, Kalamazoo, Michigan | en_US |
dc.contributor.affiliationumcampus | Ann Arbor | en_US |
dc.identifier.pmid | 8229677 | en_US |
dc.description.bitstreamurl | http://deepblue.lib.umich.edu/bitstream/2027.42/45048/1/10928_2005_Article_BF01059767.pdf | en_US |
dc.identifier.doi | http://dx.doi.org/10.1007/BF01059767 | en_US |
dc.identifier.source | Journal of Pharmacokinetics and Biopharmaceutics | en_US |
dc.owningcollname | Interdisciplinary and Peer-Reviewed |
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