title: Albumin Supplement Affects the Metabolism and Metabolism-Related Drug-Drug Interaction of Fenoprofen Enantiomers.
abstract: The influence of albumin towards the metabolism behavior of fenoprofen enantiomers and relevant drug-drug interaction was investigated in the present study. The metabolic behavior of fenoprofen enantiomers was compared in a phase II metabolic incubation system with and without bovine serum albumin (BSA). BSA supplement increased the binding affinity parameter (Km) of (R)-fenoprofen towards human liver microsomes (HLMs) from 148.3 to 214.4 μM. In contrast, BSA supplement decreased the Km of (S)-fenoprofen towards HLMs from 218.2 to 123.5 μM. For maximum reaction velocity (Vmax), the addition of BSA increased the Vmax of (R)-fenoprofen from 1.3 to 1.6 nmol/min/mg protein. In the contrast, BSA supplement decreased the Vmax value from 3.3 to 1.5 nmol/min/mg protein. Andrographolide-fenoprofen interaction was used as an example to investigate the influence of BSA supplement towards fenoprofen-relevant drug-drug interaction. The addition of 0.2% BSA in the incubation system significantly decreased the inhibition potential of andrographolide towards (R)-fenoprofen metabolism (P < 0.001). Different from (R)-fenoprofen, the addition of BSA significantly increased the inhibition potential of andrographolide towards the metabolism of (S)-fenoprofen. BSA supplement also changed the inhibition kinetic type and parameter of andrographolide towards the metabolism of (S)-fenoprofen. In conclusion, albumin supplement changes the metabolic behavior of fenoprofen enantiomers and the fenoprofen-andrographolide interaction.
authors.affiliation: Department of Emergency, First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
authors.forename: Nan
authors.initials: N
authors.lastname: Wang
authors.affiliation: Department of Orthopaedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital.
authors.forename: Feng
authors.initials: F
authors.lastname: Wang
authors.affiliation: Department of Emergency, First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Meng
authors.affiliation: Department of Emergency, First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
authors.forename: Guo-Hui
authors.initials: GH
authors.lastname: Yang
authors.affiliation: Department of Emergency, First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
authors.forename: Ju-Wu
authors.initials: JW
authors.lastname: Chen
authors.affiliation: Department of Pediatric Surgery, First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
authors.forename: Jia-Xiang
authors.initials: JX
authors.lastname: Wang
mesh_terms: D004224:Diterpenes / Q000378:metabolism / Q000493:pharmacokinetics; D004347:Drug Interactions; D005279:Fenoprofen / Q000737:chemistry* / Q000378:metabolism / Q000493:pharmacokinetics*; D006801:Humans; D007700:Kinetics; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism; D012710:Serum Albumin, Bovine / Q000378:metabolism*; D013237:Stereoisomerism
chemical_list: D004224:Diterpenes; D012710:Serum Albumin, Bovine; C030419:andrographolide; D005279:Fenoprofen
keywords: UDP-glucuronosyltransferase (UGT); albumin; andrographolide; chirality; fenoprofen