Binding of pyridostigmine bromide, N,N-diethyl-m-toluamide and permethrin, alone and in combinations, to human serum albumin.
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 microg/ml PB, DEET and permethrin, alone or in combination, were incubated with HSA at 37 degrees 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.
Abu-Qare
Aqel W
AW
Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC 27710, USA.
Abou-Donia
Mohamed B
MB
D000704:Analysis of Variance; D002800:Cholinesterase Inhibitors / Q000737:chemistry; D002851:Chromatography, High Pressure Liquid; D003671:DEET / Q000737:chemistry*; D006801:Humans; D007302:Insect Repellents / Q000737:chemistry; D007306:Insecticides / Q000737:chemistry; D026023:Permethrin / Q000737:chemistry*; D011485:Protein Binding; D011729:Pyridostigmine Bromide / Q000737:chemistry*; D012709:Serum Albumin / Q000737:chemistry*
D002800:Cholinesterase Inhibitors; D007302:Insect Repellents; D007306:Insecticides; D012709:Serum Albumin; D003671:DEET; D026023:Permethrin; D011729:Pyridostigmine Bromide