Binding of pyridostigmine bromide, N,N-diethyl-m-toluamide and permethrin, alone and in combinations, to human serum albumin

Abstract.

In this study we examined the interaction of the anti-nerve agent drug pyridostigmine bromide (PB, 3,3-dimethylaminocarbonyloxy-N-methylpyridiniyum bromide), the insect repellent DEET (N,N-diethyl-m-toluamide), and the insecticide permethrin [3-(2,2-dichloroethyl)-2,2-dimethylcyclopropanecarboxylic acid (3-phenoxyphenyl)methyl ester] in binding to human serum albumin (HSA). Concentrations between 500 ng/ml and 10 µg/ml PB, DEET and permethrin, alone or in combination, were incubated with HSA at 37°C for 60 min. Concentrations of PB, DEET and permethrin were determined using high performance liquid chromatography (HPLC). The results showed that 81.2±4.2%, and 84.6±2.5% of the initial concentration of PB was bound to HSA when incubated alone or in combination with DEET or permethrin, respectively. DEET and permethrin did not significantly interact with HSA after 1 h of incubation. Incubation of combinations of two or three compounds did not significantly alter the binding pattern of any of the compounds with HSA. These results showed that PB is highly bound to albumin protein, while the competition between PB, DEET and permethrin on binding sites of HSA as a possible site of interaction following combined administration in vivo is not likely.