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The Effect of Ethanol on the Hydrolysis of Ester-Type Drugs by Human Serum Albumin.
- Source :
-
Biological & pharmaceutical bulletin [Biol Pharm Bull] 2018 Feb 01; Vol. 41 (2), pp. 277-280. Date of Electronic Publication: 2017 Nov 27. - Publication Year :
- 2018
-
Abstract
- Human serum albumin (HSA) has two major ligand-binding sites, sites I and II, and hydrolyzes compounds at both sites. Although the hydrolytic interaction of ester-type drugs with other drugs by HSA has been reported, there are only a few studies concerning the effect of pharmaceutical excipients on the hydrolysis of ester-type drugs by HSA. In the present study, we investigated the effect of ethanol (2 vol%; 345 mM) on the hydrolysis of aspirin, p-nitrophenyl acetate, and olmesartan medoxomil, which are ester-type drugs, with 4 different lots of HSA preparations. The hydrolysis activities of HSA toward aspirin, p-nitrophenyl acetate, and olmesartan medoxomil were measured from the pseudo-first-order degradation rate constant (k <subscript>obs</subscript> ) of salicylic acid, p-nitrophenol, and olmesartan, respectively, which are the HSA-hydrolyzed products. Ethanol inhibited hydrolysis of aspirin by HSA containing low levels of fatty acids, but not by fatty acid-free HSA. Ethanol inhibited hydrolysis of p-nitrophenyl acetate by both fatty acid-free HSA and HSA containing low levels of fatty acids. In contrast, the hydrolysis of olmesartan medoxomil by HSA was insignificantly inhibited by ethanol, but inhibited not only by warfarin and indomethacin but also by naproxen, which are site I binding drugs and a site II binding drug, respectively. These results suggest that the inhibitory action of ethanol on the hydrolysis of ester-type drugs by HSA differs between site I binding drugs and site II binding drugs.
- Subjects :
- Anti-Inflammatory Agents, Non-Steroidal chemistry
Anti-Inflammatory Agents, Non-Steroidal metabolism
Anti-Inflammatory Agents, Non-Steroidal pharmacology
Anticoagulants chemistry
Anticoagulants metabolism
Anticoagulants pharmacology
Antihypertensive Agents chemistry
Antihypertensive Agents metabolism
Aspirin chemistry
Binding Sites drug effects
Drug Stability
Fatty Acids, Nonesterified chemistry
Fatty Acids, Nonesterified metabolism
Humans
Hydrolysis drug effects
Indomethacin chemistry
Indomethacin metabolism
Indomethacin pharmacology
Kinetics
Ligands
Naproxen chemistry
Naproxen metabolism
Naproxen pharmacology
Nitrophenols chemistry
Olmesartan Medoxomil chemistry
Serum Albumin, Human antagonists & inhibitors
Serum Albumin, Human chemistry
Warfarin chemistry
Warfarin metabolism
Warfarin pharmacology
Aspirin metabolism
Ethanol pharmacology
Excipients pharmacology
Nitrophenols metabolism
Olmesartan Medoxomil metabolism
Preservatives, Pharmaceutical pharmacology
Serum Albumin, Human metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1347-5215
- Volume :
- 41
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Biological & pharmaceutical bulletin
- Publication Type :
- Academic Journal
- Accession number :
- 29176265
- Full Text :
- https://doi.org/10.1248/bpb.b17-00680