title: Stability, blood partition, and protein binding of DA-5018, a new nonnarcotic analgesic.
abstract: The stability of DA-5018, a capsaicin analog as a new non-narcotic analgesic, in plasma, blood, 4% human serum albumin (HSA), and isotonic Sørensen phosphate buffer at pH 7.4 containing dextran to make 3% ('the buffer'), the blood partition of DA-5018 between plasma and blood cells, and the factors influencing the binding of DA-5018 to 4% HSA using an equilibrium dialysis technique were evaluated. DA-5018 was stable in both rat blood and plasma for up to 4 hr storage at 25 degrees C. However, DA-5018 was unstable in both dog blood and plasma; the disappearance half-lives were 1 and 1.67 hr for dog blood and plasma, respectively, when they were kept at 25 degrees C. DA-5018 seemed to be stable in 'the buffer' for up to 24 hr standing at both 25 degrees C and 37 degrees C, and in 4% HSA at 25 degrees C. However, DA-5018 was unstable in 4% HSA at 37 degrees C. DA-5018 reached equilibrium very fast between blood cells and plasma in rat blood; the mean blood cells to plasma concentration ratio was 1.31 +/- 0.0907. Although both blood and plasma concentrations of DA-5018 were unstable after incubation in dog blood, the blood cells to plasma concentration ratio was independent of incubation time; the mean value was 0.857 +/- 0.0502. Binding of DA-5018 to 4% HSA was dependent on DA-5018 concentration, buffer pH, and incubation temperature. The binding was independent of buffers containing various chloride ion concentrations. The binding of DA-5018 was dependent on alpha-1-acid glycoprotein and HSA concentrations.
authors.affiliation: Research Laboratories, Dong-A Pharmaceutical Company, Ltd., Kyunggi-Do, Korea.
authors.forename: H J
authors.initials: HJ
authors.lastname: Shim
authors.forename: J J
authors.initials: JJ
authors.lastname: Lee
authors.forename: S D
authors.initials: SD
authors.lastname: Lee
authors.forename: W B
authors.initials: WB
authors.lastname: Kim
authors.forename: J
authors.initials: J
authors.lastname: Yang
authors.forename: S H
authors.initials: SH
authors.lastname: Kim
authors.forename: M G
authors.initials: MG
authors.lastname: Lee
mesh_terms: D018712:Analgesics, Non-Narcotic / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D001773:Blood Cells / Q000378:metabolism; D001798:Blood Proteins / Q000378:metabolism*; D002211:Capsaicin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D004285:Dogs; D004355:Drug Stability; D006863:Hydrogen-Ion Concentration; D009961:Orosomucoid / Q000378:metabolism; D011485:Protein Binding; D051381:Rats; D012709:Serum Albumin / Q000378:metabolism; D013045:Species Specificity; D013696:Temperature
chemical_list: D018712:Analgesics, Non-Narcotic; D001798:Blood Proteins; D009961:Orosomucoid; D012709:Serum Albumin; C101852:DA 5018; D002211:Capsaicin