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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Human pharmacokinetics and tolerability of L-365,260, a novel cholecystokinin-B antagonist.

A study was conducted to examine the tolerability and pharmacokinetics of single and multiple oral doses of L-365,260, a novel antagonist for type B cholecystokinin (CCK) receptors and to quantify effects of selective blockade of type B CCK receptors through treatment with L-365,260 on measures of anxiety, hunger, and cognitive performance. Healthy volunteers were given single oral doses of up to 50 mg of L-365,260 and multiple oral doses of up to 25 mg every 6 hours for 10 days. Plasma concentrations of L-365,260 were quantified by means of high-performance liquid chromatography. Anxiety and hunger were assessed by visual analog scale and the Spielberger State Anxiety Index. Cognitive testing was used to evaluate attention level and short-term memory. L-365,260 was rapidly absorbed and a biphasic pattern of elimination was demonstrated with a terminal half-life (t1/2) of 8 to 12 hours. The mean (n = 6) values for peak plasma concentration (C(max)) and time to peak concentration (t(max)) of L-365,260 were 503 ng/mL and 1.25 hours, respectively, after a single 50-mg oral dose. Accumulation of L-365,260 plasma concentrations was seen after the prescribed multiple-dose regimens. Steady state was achieved after 3 days of oral administration. L-365,260 had an acceptable tolerability profile after oral administration. No changes in measures of anxiety, hunger, or short-term memory were observed at doses of L-365,260 shown to have antagonist activity at the CCK-B receptor.[1]


  1. Human pharmacokinetics and tolerability of L-365,260, a novel cholecystokinin-B antagonist. Grasing, K., Murphy, M.G., Lin, J., Swigar, M., Freedholm, D., Clarke, L., Zhang, J., Wolkowitz, O.M., Weingartner, H., Putnam, K., Seibold, J.R. Journal of clinical pharmacology. (1996) [Pubmed]
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