Biopharmaceutics & Drug Disposition 2008-07-01

Estimation of serum protein binding of compounds metabolized in serum using matrix inhibition.

Takahide Uchimura, Motohiro Kato, Rie Shiokawa, Yoshiaki Nabuchi, Kimitoshi Saito, Haruki Kinoshita

Index: Biopharm. Drug Dispos. 29(5) , 308-10, (2008)

Full Text: HTML

Abstract

It is difficult to evaluate the serum protein binding of compounds that are metabolized in rat serum, even when using ultrafiltration. Protein binding was estimated using matrix inhibition, a method that uses the change in metabolic velocity achieved by changing the free fraction of a compound in the incubation mixture by diluting the serum with phosphate buffered saline. The T(1/2) of phenyl nicotinate, benzyl nicotinate, octyl nicotinate, hexyl nicotinate, butyl nicotinate and [(3)H] compound A were 0.165, 0.780, 2.62, 3.94, 5.22 and 135 min, respectively, with protein binding values of 82.1%, 91.6%, 98.8%, 98.5%, 85.5% and 96.9%. The protein binding value of compound A estimated by ultrafiltration was 93.4%, indicating that the two methods give similar values. The matrix inhibition method is thus applicable for the evaluation of compounds metabolized in serum, and provides a simple, useful method to determine protein binding.

Related Compounds

  • Benzyl nicotinate...

Related Articles:

Effects of water activity and low molecular weight humectants on skin permeability and hydration dynamics - a double-blind, randomized and controlled study.

2014-10-01

[Int. J. Cosmet. Sci. 36(5) , 412-8, (2014)]

[On interactions of drugs on and in the skin/comparative studies on the mutual influences of ethyleneglycol-monosalicylate and benzylnicotinate (author's transl)].

1981-01-01

[Derm. Beruf Umwelt. 29(6) , 161-7, (1981)]

Kinetics of blood flow after topical application of benzyl nicotinate on different anatomic sites.

2006-11-01

[Arch. Dermatol. Res. 298(6) , 291-300, (2006)]

Skin oxygenation after topical application of liposome-entrapped benzyl nicotinate as measured by EPR oximetry in vivo: influence of composition and size.

2003-01-01

[AAPS PharmSci 5(1) , E2, (2003)]

Blood flow enhancement in skin or oral mucosa after the topical application of liposome entrapped rubifacient as measured by EPR oximetry in vivo: the influence of size and liposome composition.

2002-01-01

[Cell Mol. Biol. Lett. 7(2) , 256-8, (2002)]

More Articles...