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

Noninvasive assessment of portal-systemic shunting: evaluation of a method to investigate systemic availability of oral glyceryl trinitrate by digital plethysmography.

The systemic availability of oral glyceryl trinitrate may be a measure of the fraction of portal blood bypassing the hepatocytes through portal-systemic shunts. In order to test this hypothesis without the need for blood sampling, measurements of drug concentrations in plasma were replaced by assessments of pharmacologic effects by using digital plethysmography. Dose-response curves resulting from graded intravenous infusions of glyceryl trinitrate (8 and 25 microgram/min) were used as standard of comparison for the pharmacologic response resulting from an oral dose of 800 microgram. In 9 normal volunteers, systemic availability of oral glyceryl trinitrate was 2 +/- 4% SD. In 7 patients with end-to-side portacaval shunts it was 94 +/- 18%, in 3 patients with distal splenorenal shunts 57 +/- 11%, and in 10 patients with cirrhosis of the liver it varied between 15% and 85%. Systemic availability of glyceryl trinitrate was negatively correlated with the initial plasma disappearance rate of sulfobromophthalein (r = -0.72, p less than 0.01). No significant correlation was found with the galactose elimination capacity (r = -0.12, n = 17). The lack of systemic availability of glyceryl trinitrate in healthy volunteers together with an availability close to 100% after end-to-side shunts is compatible with a very high hepatic extraction of the test compound by the normal liver, and with the idea that the systemic availability of of oral glyceryl trinitrate comes close to representing portal-systemic shunting. The procedure is rapid, essentially noninvasive, and well tolerated by patients.[1]


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