Plasma substitutes physicochemical properties

Benzoic acids substituted with a basic side chain also are also of interest as pro-moieties whose physicochemical properties and rates of enzymatic hydrolysis can readily be modulated. A number of drugs have been converted to prodrugs with this type of pro-moiety, e.g., hydrocortisone, prednisolone, acyclovir, chloramphenicol, and paracetamol [148] [149], These prodrugs appear well suited as parenteral formulations, being water-soluble, stable in slightly acidic solution, and readily hydrolyzed enzymatically. As examples, we consider here the hydrolysis in human plasma of a number of (aminomethyl)ben-zoates of metronidazole (8.109-8.115, Sect. 8.5.5.1, Table 8.9) [138], These prodrugs are very rapidly activated, which may be beneficial for parenteral administration. However, this type of pro-moiety may be cleaved too rapidly after oral administration to be of interest for poorly absorbed drugs. 

The pathomechanism of HES-induced anaphylactoid reactions is unknown. Since HES has been in general clinical use for a comparatively short time, only a few data are available for critical evaluation of the triggering mechanisms of adverse reactions. From the physicochemical properties of HES a few possible mechanisms may, however, be visualized. Comparing the occurrence in humans of preformed antibodies reactive with plasma substitutes, it is evident that both titers and frequency are highest for gelatin, intermediate for dextran, and lowest for HES. In this connection, it is interesting to note that upon rapid infusion of HES into hu-... 

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