Two topical corticosteroids, clobetasol propionate and clobetasone butyrate, have been studied in hairless mice for their effects on DNA synthesis in the epidermis, thymus and spleen. Following topical application, both clobetasol propionate and clobetasone butyrate showed significant activity at the site of application throughout the range of concentrations tested (20 microliters; 0.0001-0.1%; 20 ng to 20 micrograms). However, whereas 20 ng clobetasol propionate also elicited significant effects in the distal (untreated) epidermis and the thymus, more than 2 micrograms of clobetasone butyrate were required to produce similar effects in these tissues. This finding was supported by the results obtained following intravenous administration of equivalent doses (0.01 and 0.001%; 200 microliters dose) of the same two steroids. Only clobetasol propionate showed significant activity in the epidermis and thymus. Clobetasone butyrate showed slight, non-significant effects in the epidermis at the highest concentration (200 microliters; 0.01%), but not in the thymus or spleen. An unexpected finding was that the effects following intravenous injection were generally lower than those following topical application. In conclusion, these results establish that (a) effects on DNA synthesis in the epidermis at a site distal to the application site are indicative of systemic activity from topically applied corticosteroids, (b) the thymus is especially sensitive to corticosteroids eliciting systemic effects and (c) an equivalent dose of a topical corticosteroid administered intravenously produces less inhibition of thymic and epidermal DNA synthesis than the same dose applied topically.

1. The pharmacokinetics and fate of 3H-trospectomycin sulphate, a novel aminocyclitol antibiotic, were examined in male and female rats after intramuscular (i.m.), intravenous (i.v.) and subcutaneous (s.c.) dosing. 2. Total radioactivity levels in plasma were associated with unchanged trospectomycin. Two radioactive components were found in urine, one was indistinguishable from trospectomycin and the other was probably a degradation product formed after excretion or during storage rather than a metabolite. 3. The disappearance of drug from plasma followed a biphasic pattern with half lives of 0.3-0.4 h and 45-80 h and a large distribution volume, which indicated some retention of drug by tissues. Clearance rates were within the normal range for glomerular filtration rate, which indicated that the primary process of elimination is filtration of unchanged drug. 4. Excretion was initially rapid (greater than 40% by 4 h) and mainly into urine (faecal excretion greater than 20%). Urinary excretion was significantly larger in males than females but faecal excretion was significantly smaller, so that there was no significant difference in total excretion. 5. The bioavailability following s.c. dosing was only approximately 75% but there were few other biologically significant differences between the routes of administration. Absorption following i.m. and s.c. dosing was rapid. 6. Clearance rate and volume of distribution were higher in males than females. Over the dose range 50-200 mg/kg the pharmacokinetics appeared to be mostly linear.

Variable amounts of food have been observed in the stomachs of male rats following an overnight fast. The effects of diet and diet type on the amount of residual food left in the stomach and on fat deposition and liver weight in the male rat were investigated. The implications of these results on metabolism and pharmacokinetic studies are discussed.