Absorption, Distribution and Excretion of Pentaerythritol and Pentaerythritol Tetranitrate by Mice

Abstract

PENTAERYTHRITOL AND PETN METABOLISM 311 tin. The quantitative precipitin curves obtained with rabbit anti-ferritin and ferritin are characterized by a sharp rise in N precipitated by increasing addition of N in the antibody excess zone, and a very slow decline in N precipitated in the region of increasing antigen excess. This type of curve, previously described(2) and confirmed in these experiments, makes determination of the zone of equivalence more difficult. The quantitative isotope precipitin curve provides an advantageous method of antibody determination with chicken or rabbit anti-ferritin systems since the anti-ferritin content of a serum can be expressed as pg N of antigen precipitated per ml of antiserum.Chicken anti-ferritin contains 3 immunoglobulins which react with ferritin in precipitin arcs, demonstrated by iron staining or P I F autoradiography. This heterogeneity of chicken antisera has been previously described (8) in the chicken anti-insulin system. Attempts to separate these antibodies for further characterization are in progress. The use of iron staining of complexes of antiferritin immunoglobulins and ferritin provides a method of study of antibodies similar to autoradiographic immunoelec trophoresis without involving the use of radioactive labeled antigens or antibodies.Summary. Gel filtration was used to obtain a preparation of horse spleen ferritin apparently free of antigenic contaminants. The purified ferritin was labeled with P1. Quantitative isotope precipitin curves with rabbit and chicken anti-ferritin are described. ?"he staining of ferritin iron in ferritin reacting with immunoglobulins of electrophoretic p r e p arations was used to show the heterogeneity of chicken antibodies in the primary and secondary response against ferritin.Although pentaerythritol tetranitrate (PETN) has been used extensively for many years to prevent angina pectoris, there is a dearth of information about its metabolism. One of the difficulties has been the lack of assay methods for the intact PETN molecule. Previous investigators demonstrated PETN absorption by the difference between the dose administered to rats and the subsequent nitrate content of the gastrointestinal tract (1) and by nitrate and nitrite assays of the blood of humans who ingested the drug (2,3,4). Since these approaches omit the intermediary metabolism of PETN, they preclude furtherance of our interest in elucidating the mechanism of action of this drug.at UNIV CALIFORNIA SAN DIEGO on June 7, 2015 ebm.sagepub.com Downloaded from

Perspectives on Pentaerythritol Tetranitrate (PETN) Decomposition

“…Although thermal decomposition studies do not readily identify PE and its nitrated congeners, a number of pharmacokinetic studies identify these species as the primary biological metabolites of PETN. 43,44,45 The hydrolysis pathway (Eq. 4), which involves chemical attack of the ester oxygen and thereby forming an alcohol end group, has been shown to occur under acidic, neutral, and basic conditions.…”

“…4), which involves chemical attack of the ester oxygen and thereby forming an alcohol end group, has been shown to occur under acidic, neutral, and basic conditions. 43,46 An in vitro method to produce PETN hydrolysis products has been demonstrated by Basch et al 17 Their procedure involved dissolving PETN in a dioxane-water (82:18) solution and adding 1% by volume concentrated HCl, which was then refluxed for 6 h. This solution was neutralized with Ca(OH) 2 and dioxane solution, dried, and then the PE congeners were extracted using ethanol. Scission of the O-NO 2 bond is reported to have an E A as low as 35 kcal/mole under nearambient conditions.…”