Half-life of compound

Figure 3.29 Effect of chronic dosing with a foreign compound on its plasma level. Half-life of compound is one hour. Upper curve shows the effect of dosing every 30 minutes and lower curve the effect of a dosage interval of two hours.

By far the greatest number of reports have referred to the anti-inflammatory activity found for a variety of 1,2-benzothiazines.15 An initial report by Lombardino et al.9 indicated that potent anti-inflammatory activity was present in a series of 4-hydroxy-2H-l,2-benzothiazine-3-carboxanilide 1,1-dioxides. Antiedema activity in a rat model indicated that carboxanilide 132 (CP-14, 304) was twice as potent as the standard anti-inflammatory agent phenylbutazone. This observation on compound 132 was later confirmed and extended by others.17,85 Studies of the metabolism of compound 132 in animals indicated that a major metabolite resulted from hydroxylation of the carboxanilide moiety.86 The plasma half-life of compound 132 was found to be 21 hours in man.86... 

Fig. 38. Chemiluminescence properties of the phenolic anions of two substituted adamantyl naphthyl dioxetanes. The emission wavelength and half-life of compound (a) are 550 nm and 23 min, respectively, while the corresponding values for compound (b) are 459 nm and 9 sec. These data are taken from Edwards et at. (El).

Thirty isotopes are recognized. Only one stable isotope, 1271 is found in nature. The artificial radioisotope 1311, with a half-life of 8 days, has been used in treating the thyroid gland. The most common compounds are the iodides of sodium and potassium (KI) and the iodates (KIOs). Lack of iodine is the cause of goiter. 

Evidence from the viscosities, densities, refractive indices and measurements of the vapour pressure of these mixtures also supports the above conclusions. Acetyl nitrate has been prepared from a mixture of acetic anhydride and dinitrogen pentoxide, and characterised, showing that the equilibria discussed do lead to the formation of that compound. The initial reaction between nitric acid and acetic anhydride is rapid at room temperature nitric acid (0-05 mol 1 ) is reported to be converted into acetyl nitrate with a half-life of about i minute. This observation is consistent with the results of some preparative experiments, in which it was found that nitric acid could be precipitated quantitatively with urea from solutions of it in acetic anhydride at —10 °C, whereas similar solutions prepared at room temperature and cooled rapidly to — 10 °C yielded only a part of their nitric acid ( 5.3.2). The following equilibrium has been investigated in detail ... 

The existence of the XeCHg [34176-86-8] cation has been estabtished ia the gas phase. The Xe—C bond energy of the XeCHg cation has been estimated to be 180 A 33 kJ/mol (112) and more recently, 231 A 10 kJ/mol (113) by ion cyclotron resonance. The compound Xe(CF3)2 [72599-34-9] is reported to be a waxy white sotid having a half-life of ca 30 min at room temperature (114). The synthesis iavolved the addition of XeF2 to a tritiuoromethyl plasma, but the characterization of this compound is limited and has not been iadependently confirmed. 

Alkyl mercury compounds in the blood stream are found mainly in the blood cehs, and only to a smah extent in the plasma. This is probably the result of the greater stabhity of the alkyl mercuric compounds, as well as their pecuflar solubiUty characteristics. Alkyl mercury compounds affect the central nervous system and accumulate in the brain (17,18). Elimination of alkyl mercury compounds from the body is somewhat slower than that of inorganic mercury compounds and the aryl and alkoxy mercurials. Methylmercury is eliminated from humans at a rate indicating a half-life of 50—60 d (19) inorganic mercurials leave the body according to a half-life pattern of 30—60 d (20). Elimination rates are dependent not only on the nature of the compound but also on the dosage, method of intake, and the rate of intake (21,22). 

Decay products of the principal radionuclides used in tracer technology (see Table 1) are not themselves radioactive. Therefore, the primary decomposition events of isotopes in molecules labeled with only one radionuclide / molecule result in unlabeled impurities at a rate proportional to the half-life of the isotope. Eor and H, impurities arising from the decay process are in relatively small amounts. Eor the shorter half-life isotopes the relative amounts of these impurities caused by primary decomposition are larger, but usually not problematic because they are not radioactive and do not interfere with the application of the tracer compounds. Eor multilabeled tritiated compounds the rate of accumulation of labeled impurities owing to tritium decay can be significant. This increases with the number of radioactive atoms per molecule. 

Sotalol is rapidly and almost completely (>90%) absorbed. Bioavahabhity of absorbed dmg is 89—100%. Peak plasma levels are achieved in 2—4 h. Sotalol is 50% bound to plasma proteins. Plasma half-life of the compound is about 5.2 h. No metabolites of sotalol have been identified indicating littie metabolism. The dmg is excreted mainly by the kidneys (80—90%) and about 10% is eliminated in the feces. The plasma half-life is prolonged in patients having renal failure. Kinetics of the compound are not affected by changes in liver function (1,2). Sotalol has ah the adverse effects of -adrenoceptor blockers including myocardial depression, bradycardia, transient hypotension, and proarrhythmic effects (1,2). 

Discrimination between exposed and unexposed areas in this process requires the selection of thia zolidine compounds that do not readily undergo alkaline hydrolysis in the absence of silver ions. In a study of model compounds, the rates of hydrolysis of model /V-methyl thia zolidine and A/-octadecyl thiazolidine compounds were compared (47). An alkaline hydrolysis half-life of 33 min was reported for the /V-methyl compound, a half-life of 5525 min (3.8 days) was reported for the corresponding V/-octadecyl compound. Other factors affecting the kinetics include the particular silver ligand chosen and its concentration (48). Polaroid Spectra film introduced silver-assisted thiazolidine cleavage to produce the yellow dye image (49), a system subsequentiy used in 600 Plus and Polacolor Pro 100 films. 

Dmgs, such as opiates, may undergo metabolism both in the intestinal wall and in the fiver (first-pass metabolism). The metabolism may be extensive and considerably reduce the amount of dmg reaching the systemic circulation. Alternatively, the metabolite may be metabofically active and contribute significantly to the action of the parent dmg. Some compounds undergo enterohepatic circulation in which they are secreted into the GI tract in the bile and are subsequently reabsorbed. Enterohepatic circulation prolongs the half-life of a dmg. 

Dihydropyridazines are known as labile intermediates, and lose nitrogen at -78 °C with a half-life of 30 seconds or less. On the other hand, the corresponding 2-oxides are stable compounds which lose N2O only at 300 °C or above (77JA8505). 

This compound is less stable than 5 and reverts to benzene with a half-life of about 2 days at 25°C, with AH = 23 kcal/mol. The observed kinetic stability of Dewar benzene is surprisingly high when one considers that its conversion to benzene is exothermic by 71 kcal/mol. The stability of Dewar benzene is intimately related to the orbital symmetry requirements for concerted electrocyclic transformations. The concerted thermal pathway should be conrotatory, since the reaction is the ring opening of a cyclobutene and therefore leads not to benzene, but to a highly strained Z,Z, -cyclohexatriene. A disrotatory process, which would lead directly to benzene, is forbidden. ... 

Another important storage depot for toxic compounds is the skeleton. In particular, cadmium and lead bind and accumulate in the bone tissue from which they are released very slowly. The half-life of elimination of cadmium is several years, the half-life of lead is several months. 

In addition to the elimination rate constant, the half-life (T/i) another important parameter that characterizes the time-course of chemical compounds in the body. The elimination half-life (t-1/2) is the time to reduce the concentration of a chemical in plasma to half of its original level. The relationship of half-life to the elimination rate constant is ti/2 = 0.693/ki,i and, therefore, the half-life of a chemical compound can be determined after the determination of k j from the slope of the line. The half-life can also be determined through visual inspection from the log C versus time plot (Fig. 5.40). For compounds that are eliminated through first-order kinetics, the time required for the plasma concentration to be decreased by one half is constant. It is impottant to understand that the half-life of chemicals that are eliminated by first-order kinetics is independent of dose. ... 

These small-molecule thiols serve to transfer NO from erythrocytes to endothelial receptors, where it acts to relax vascular tension. NO itself is a reactive free-radical compound whose biological half-life is very short (1-5 sec). S-nitrosoglutathione has a half-life of several hours. 

The compound is thermally unstable, and decomposes with a half-life of about 25 s at room temperature ... 

Fewer compounds with Xe-C bonds have been characterized. The first to be claimed was synthesized by the plasma reaction of XeF2 with CF3 radicals the volatile waxy white solid produced, Xe(CF3)2, decomposed at room temperature with a half-life of about 30 min. " ... 

Almost all types of cell can be used to convert an added compound into another compound, involving many forms of enzymatic reaction including dehydration, oxidation, hydroxyla-tion, animation, isomerisation, etc. These types of conversion have advantages over chemical processes in that the reaction can be very specific, and produced at moderate temperatures. Examples of transformations using enzymes include the production of steroids, conversion of antibiotics and prostaglandins. Industrial transformation requires the production of large quantities of enzyme, but the half-life of enzymes can be improved by immobilisation and extraction simplified by the use of whole cells. 

The effects of leukotrienes can be blocked at several levels. Inhibitors of FLAP or 5-LO inhibit LT synthesis at all levels. However, FLAP antagonists developed to date have been too hepatotoxic for human use. Zileuton, a 5-LO synthase inhibiting drug, also demonstrated some hepatotoxicity in a small percentage of patients, which was nonetheless entirely reversible. However, the short half-life of this compound requires four times daily... 

Diugs with metabolic interactions that can enhance the half-life of active compounds. An example of this regimen is the interaction between azole- and vitamin D-deiivatives that inhibit the metabolism of retinoids in skin cells leading to increased intracellular amounts of active RA-isomers. Further study and the identification of novel interactions of this type ofdtug interaction is of great clinical interest since they may decrease the dose of retinoids required for efficacy thereby also reducing the risk of side effects of the retinoids. 

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