2000 IMS Health Hospital Pharmacy Review: Leading Dollar Volume Pharmaceuticals

Roman, Kathleen M

doi:10.1177/001857870103600702

Hosp Pharm

2001

DOI: 10.1177/001857870103600702

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2000 IMS Health Hospital Pharmacy Review: Leading Dollar Volume Pharmaceuticals

Kathleen M Roman¹

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Blood Acylpeptide Hydrolase Activity Is a Sensitive Marker for Exposure to Some Organophosphate Toxicants

Quistad

Klintenberg

Casida

2005

Toxicological Sciences

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Acylpeptide hydrolase (APH) unblocks N-acetyl peptides. It is a major serine hydrolase in rat blood, brain, and liver detected by derivatization with (3)H-diisopropyl fluorophosphate (DFP) or a biotinylated fluorophosphonate. Although APH does not appear to be a primary target of acute poisoning by organophosphorus (OP) compounds, the inhibitor specificity of this secondary target is largely unknown. This study fills the gap and emphasizes blood APH as a potential marker of OP exposure. The most potent in vitro inhibitors for human erythrocyte and mouse brain APH are DFP (IC(50) 11-17 nM), chlorpyrifos oxon (IC(50) 21-71 nM), dichlorvos (IC(50) 230-560 nM), naled (IC(50) 370-870 nM), and their analogs with modified alkyl substituents. (3)H-diisopropyl fluorophosphate is a potent inhibitor of mouse blood and brain APH in vivo (ED(50) 0.09-0.2 mg/kg and 0.02-0.03 mg/l for ip and vapor exposure, respectively). Mouse blood and brain APH and blood butyrylcholinesterase (BChE) are of similar sensitivity to DFP in vitro and in vivo (ip and vapor exposure), but APH inhibition is much more persistent in vivo (still >80% inhibition after 4 days). The inhibitory potency of OP pesticides in vivo in mice varies from APH selective (dichlorvos, naled, and trichlorfon), to APH and BChE selective (profenofos and tribufos), to ChE selective or nonselective (many commercial insecticides). Sarin administered ip at a lethal dose to guinea pigs inhibits blood acetylcholinesterase and BChE completely but erythrocyte APH only partially. Blood APH activity is therefore a sensitive marker for exposure to some but not all OP pesticides and chemical warfare agents.

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Blood Acylpeptide Hydrolase Activity Is a Sensitive Marker for Exposure to Some Organophosphate Toxicants

Quistad

Klintenberg

Casida

2005

Toxicological Sciences

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show abstract

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2000 IMS Health Hospital Pharmacy Review: Leading Dollar Volume Pharmaceuticals

Cited by 1 publication

References 0 publications

Blood Acylpeptide Hydrolase Activity Is a Sensitive Marker for Exposure to Some Organophosphate Toxicants

Blood Acylpeptide Hydrolase Activity Is a Sensitive Marker for Exposure to Some Organophosphate Toxicants

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