Solubility in vivo

Avizafone, the peptide between the open form of diazepam (Valium ) and L-lysine bears two primary amino functions which can be salified (by HCl) and thus render the compound freely water soluble. In vivo generation of... 

Bass L A, Lanahan M V, Duncan J R, et al. (1998). Identification of the soluble in vivo metabolites of indium-lll-diethylenetriaminepentaacetic acid-D-Phe -octreotide. Bioconjug. Chem. 9 192-200. 

It has been proposed that, when the solubility of the parent compound is less than Img/mL in its unionized form (intrinsic aqueous solubility), in vivo absorption may be poor. Where the intrinsic solubility is between 1 mg/ mL and lOmg/mL, salt formation may sometimes be desirable to ensure good absorption. Salts are rarely required when the aqueous solubility is 10 mg/mL or greater, unless other physical properties are poor. 

Active substances that are dissolved in water are, if they remain in solution, immediately available for absorption after taking on an empty stomach. If they precipitate in the acidic environment of the empty stomach the precipitation will often be so fine that it easily passes the closed pylorus and re-dissolves, after which rapid absorption is still possible. The pharmaceutical availability (actually the dissolution rate of the solid substance) of suspensions for oral use depends on many factors including solubility in vivo, the crystal modification and the particle size and the viscosity of the suspension. In practice it occurs that an active substance (such as phenobarbital) may be formulated as a suspension in water or as a solution in a lipophilic solvent such as acetem (see Sect. 23.3.6). Beware that changing from a suspension into a solution may cause a great increase in absorption rate and thus cause a change in pharmacodynamics. 

LynestrenoL Lynestrenol (73) has been used in oral contraceptives and to treat menstrual disorders. It is converted in vivo to its active metabohte norethindrone (102,103). It can be recrystallized from methanol, and is soluble in ethanol, ether, chloroform, and acetone, and insoluble in water (102). The crystal stmcture (104) and other spectral and analytical data have been reported for lynestrenol (62). 

The thiol form (12) is susceptible to oxidation (see Fig. 2). Iodine treatment regenerates thiamine in good yield. Heating an aqueous solution at pH 8 in air gives rise to thiamine disulfide [67-16-3] (21), thiochrome (14), and other products (22). The disulfide is readily reduced to thiamine in vivo and is as biologically active. Other mixed disulfides, of interest as fat-soluble forms, are formed from thiamine, possibly via oxidative coupling to the thiol form (12). 

Because of the increasing emphasis on monitoring of environmental cadmium the detemiination of extremely low concentrations of cadmium ion has been developed. Table 2 Hsts the most prevalent analytical techniques and the detection limits. In general, for soluble cadmium species, atomic absorption is the method of choice for detection of very low concentrations. Mobile prompt gamma in vivo activation analysis has been developed for the nondestmctive sampling of cadmium in biological samples (18). 

Recently, water-soluble protein fractions, isolated from extracts of bone matrix, were incorporated into a collagen matrix and shown to induce bone (67,68) and cartilage formation both in vitro and in vivo (69,70). In the latter studies, in the absence of the collajgen delivery system, the proteins were incapable of inducing cartilage formation in vivo when implanted intramuscularly into mice. The success of this approach appears to depend on delivering the active agents at an effective dose over an extended time period. 

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