Title: Correlation Between the Intravenous Administration of Methemoglobin Formers and in Vitro Monitoring of Methemoglobin Levels
Abstract: Abstract : Direct acting methemoglobin forming compounds, such as the well known sodium nitrite, can be added to whole blood leading to in vitro formation of methemoglobin. In the canine model the rate of formation of methemoglobin in vitro is similar to the rate of methemoglobin formation obtained during rapid intravenous infusion. The in vitro addition of direct acting p- aminopropiophenone derivatives to blood obtained from unanesthetized dogs forms methemoglobin at rates similar to the intravenous infusion of the same compounds in the same dogs. These studies demonstrate that in vitro addition of compounds to whole blood can be used to rapidly obtain an estimate of the rate of formation of methemoglobin and the approximate whole blood concentration of an unknown compound required to induce desired levels of methemoglobin. Since this in vitro system only responds to direct formers of methemoglobin it is possible to determine if a compound which forms methemoglobin in-vivo does so by a direct effect - or if the compound induces methemoglobin through a metabolite. If a series of methemoglobin formers are to be evaluated the in vitro system can be used to identify the most potent and rapid acting of the methemoglobin formers. A comparison of in vitro vs. in-vivo activity may identify differences due to altered formation of methemoglobin or to pharmacokinetic differences. Another in vitro system has been developed which is useful in monitoring the rate of interaction between the cyanide ion and methemoglobin. This additional in vitro system can be used to determine if the methemoglobin which is formed by one of a series of compounds will interact with cyanide at the same rate as methemoglobin which is induced by sodium nitrite.
Publication Year: 1993
Publication Date: 1993-05-13
Language: en
Type: article
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