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

The effects of co-administration of benzhexol on the peripheral pharmacokinetics of oral levodopa in young volunteers.

1. The effects of benzhexol on the absorption and pharmacokinetics of an oral dose of levodopa have been studied in 10 young healthy volunteers. Subjects were given a suspension of levodopa (250 mg) 90 min after either benzhexol (5 mg) or placebo in a randomized cross over design with doses separated by at least 1 week; on each occasion carbidopa was given 1 h before and 5 h after the dose of levodopa. Soluble paracetamol and radiolabelled DTPA were given with the levodopa as markers of gastric emptying. 2. Most subjects showed two peaks in the levodopa plasma concentration-time curve on the placebo day, with the second minor peak occurring 1-2 h after the dose. After benzhexol administration all subjects showed two or more peak levodopa concentrations in plasma. Benzhexol administration caused a significant decrease in the maximum concentration (43%; P < 0.05) of the initial peak and an increase (22%; P < 0.1) in the maximum concentration of the second peak. This change in absorption profile caused by benzhexol significantly altered the ratios of the second peak compared with the initial peak for both the maximum concentrations (P < 0.02) and for the AUC values (P < 0.05). Benzhexol administration did not affect the total AUC of levodopa (7.30 +/- 1.09 vs 7.19 +/- 1.26 micrograms ml-1 h; means +/- s.d.). 3. The plasma concentration-time curves for paracetamol showed similar profiles to those for levodopa and the ratios of the peak concentrations and AUC values for the second peak compared with the initial peak were increased significantly by benzhexol administration (P < 0.05). The total AUC of paracetamol was not affected by benzhexol administration (39.4 +/- 8.2 vs 40.0 +/- 8.9 micrograms ml-1 h; mean +/- s.d.) 4. Benzhexol altered the gastric emptying profile, shown by gamma-scintigraphy, with a reduced extent of initial emptying prior to the establishment of the plateau which is characteristic of levodopa administration in the fasting state. In consequence the ratio of the second to the initial phase of emptying was significantly higher (P < 0.01) following benzhexol treatment. 5. Benzhexol reduces the initial phase of gastric emptying after a dose of levodopa so that there is a decrease in the initial peak and a greater proportion of the dose is absorbed subsequently following the second phase of gastric emptying which occurs approximately 1 h later. Theoretically, this altered concentration-time profile could be an advantage for some patients with Parkinson's disease.[1]


  1. The effects of co-administration of benzhexol on the peripheral pharmacokinetics of oral levodopa in young volunteers. Roberts, J., Waller, D.G., von Renwick, A.G., O'Shea, N., Macklin, B.S., Bulling, M. British journal of clinical pharmacology. (1996) [Pubmed]
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