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Biomedical subjects

L G Brookes

Publications and source records attributed to L G Brookes.

At least 19 recordsLinked to original sources
PubMed1996

Food intake and dosage level, but not tablet vs solution dosage form, affect the absorption of metformin HCl in man.

The pharmacokinetics of four single-dose treatments of the metformin administered orally (as the HCl salt) were compared in 24 healthy subjects: 500 mg and 850 mg tablets and 850 mg solution fasting and 850 mg tablet with food. Solution and tablet formulations are bioequivalent. Bioavailability of a 500 mg tablet is 14% greater than that of an 850 mg tablet. Compared with the fasting state, bioavailability is 24% lower, and the peak concentration delayed about 37 min when an 850 mg tablet is administered with food.

Adult↗
PubMed1981

The effects of topical and systemic glucocorticosteroids on DNA synthesis in different tissues of the hairless mouse.

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.

Administration, Topical↗
PubMed1979

The effects on epidermal DNA synthesis of topically applied cycloheximide.

An animal model for investigating topically applied epidermal cytotoxic drugs to determine optimum therapeutic doses and schedules is described. It is used here to examine the effects of cycloheximide on epidermal DNA synthesis, as measured by 3H-thymidine incorporation in vivo, in terms of dose/response and activity/time profiles and potential systemic toxicity.

Administration, Topical↗
PubMed1979

Relative effects of different surfactants on intestinal absorption and the release of proteins and phospholipids from the tissue.

The actions of anionic, cationic and non-ionic surfactants on the absorptive capability of rat jejunal tissue in vivo were compared with their effects on the amounts of protein and phospholipid released from the mucosal surface under the same conditions. Release of a comparatively small amount of protein was accompanied by large increases in the absorption rates of both L-valine and salicylate, whereas much larger quantities of phospholipid were released before any increase in absorption were observed. Much of the released material appeared to be derived from mucus which was partly degraded after exposure to the higher concentrations of surfactants. The liberation of cholesterol by high concentrations of anionic surfactants suggested that some disruption of the mucosal membrane occurred under those conditions. The relative potency of the surfactants in stimulating both absorption of the solutes and the release of polypeptides and lipids followed the order: anionic greater than non-ionic greater than cationic. The possible pharmaceutical relevance of these findings is discussed.

Animals↗
PubMed1979

Serum and peritoneal fluid concentrations of clindamycin and lincomycin in the mouse.

Serum concentrations of drug were obtained at various times after intramuscular dosing of healthy mice with either clindamycin or lincomycin hydrochlorides. Washings from the peritoneal cavity were taken at the same time as the serum samples. Changes in drug concentration in the peritoneal fluid with time mimic those for the serum, but concentrations in peritoneal fluid are much greater than the corresponding serum concentrations. The total volume of peritoneal fluid was estimated to be 0.05 ml.

Animals↗
PubMed1978

An animal model for evaluating the local and systemic effects of topically applied corticosteroids on epidermal DNA synthesis.

A simple animal model for studying topically applied glucocorticosteroids for their effect on epidermal DNA synthesis is described. It is designed so that their potential for systemic side effects may be predicted and its usefulness in this respect is illustrated by the results obtained with two of the steroids investigated. One, a new formulation Temetex, is predicted to have considerable systemic potential. The other, Molivate, is remarkable for having moderate local, without demonstrable systemic activity.

Administration, Topical↗