The inactivation of HIV by gamma-radiation was studied in frozen and liquid plasma; a reduction of the virus titer of 5 to 6 logs was achieved at doses of 5 to 10 Mrad at -80 degrees C and 2.5 Mrad at 15 degrees C. The effect of irradiation on the biologic activity of a number of coagulation factors in plasma and in lyophilized concentrates of factor VIII (FVIII) and prothrombin complex was examined. A recovery of 85 percent of the biologic activity of therapeutic components present in frozen plasma and in lyophilized coagulation factor concentrates was reached at radiation doses as low as 1.5 and 0.5 Mrad, respectively. As derived from the first-order radiation inactivation curves, the radiosensitive target size of HIV was estimated to be 1 to 3 MDa; the target size of FVIII was estimated to be 130 to 160 kDa. Gamma radiation must be disregarded as a method for the sterilization of plasma and plasma-derived products, because of the low reduction of virus infectivity at radiation doses that still give acceptable recovery of biologic activity of plasma components.

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The metabolic pattern of dydrogesterone was investigated in the rat, dog, mouse, rabbit and rhesus monkey. The drug was administered orally in 3H-labelled form. Following enzymatic hydrolysis of conjugates the radioactive metabolites were extracted from the urine, and in rat and dog also from bile. The separation method used for the development of the metabolite patterns was reversed-phase high performance liquid chromatography. Dydrogesterone and 4 derivatives, known or suspected to be metabolites, were used as marker substances. In all the species a substantial portion of the urinary or biliary radioactivity was too polar to be extracted, or it was not resolved in the chromatographic system used. The radioactivity which did develop into a pattern coincided with two or more of the marker substances. Only in the monkey, the pattern contained a peak of some substance which did not coincide with any marker. The urinary patterns of rat, dog, and mouse differed substantially, from each other as well as from those of rabbit and monkey. The patterns for the latter two animals showed certain similarities, both to each other and to the human urinary pattern as reconstructed from previous studies. It is concluded that with regard to the metabolic fate of dydrogesterone, the rabbit resembles man more than does any other species.

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