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At least 19 recordsLinked to original sources
PubMed1984

Kinetics and bioavailability of N-nitrosodiethanolamine after intravenous and cutaneous administration to rats.

Male CD-COBS rats were given N-nitrosodiethanolamine (NDELA) by intravenous or cutaneous administration at a dose of 5 mg/kg. Blood and liver were analysed for NDELA at various times after administration. The excretion of unchanged NDELA and its acidic metabolite N-(2-hydroxyethyl)-N-carboxymethylnitrosamine (ECMN) was determined in urine for 24 hr after treatment. The semilogarithmic blood concentration-time plot after iv injection showed a triphasic profile indicating that a three-compartment model may adequately describe the kinetics of this compound. After cutaneous application NDELA was rapidly absorbed through the skin, and the absolute bioavailability was calculated to be 27% from blood data, and to be 32% (NDELA + ECMN) from urine data. Hepatic NDELA levels reflected blood levels after both treatments, indicating that this organ does not accumulate NDELA to a significant extent. Urinary excretion of unchanged NDELA after iv and cutaneous administration was 83 and 25% of the administered dose, respectively. ECMN excretion was 4.9 and 2.5% of the administered dose after iv and cutaneous administration, respectively.

Animals↗
PubMed1993

[Tissue and systemic diffusion of idrocilamide after cutaneous administration].

Experimental findings have demonstrated that idrocilamide exhibits antiinflammatory and muscle relaxant properties due at least in part to tissular effects. Percutaneous diffusion of a 10% glycero-alcoholic idrocilamide solution was studied in ten patients scheduled to undergo total knee replacement. Four 200-mg doses of idrocilamide were applied to the suprapatellar area at 12-hour intervals before surgery. Pain was evaluated using a visual analog scale before and after treatment. Surgery was performed 1.75 to 3.5 hours after the last idrocilamide dose. Idrocilamide was assayed using high performance liquid chromatography in tissue, plasma, and joint fluid specimens taken during the surgical procedure. Topical administration of idrocilamide on healthy skin produced significant concentrations of the drug in all the tissue specimens, including subcutaneous fat, muscle, tendon, synovium, and knee capsule. Tissue levels were consistently higher than synovial fluid and plasma levels, indicating that little systemic diffusion occurred. Idrocilamide levels in potential target tissues might influence clinical effects.

Administration, Cutaneous↗
PubMed1995

Disposition and metabolism of acrylic acid in C3H mice and Fischer 344 rats after oral or cutaneous administration.

Acrylic acid (AA) is used in large amounts to produce acrylic esters and polymers. Here we report on the disposition and metabolism of [1-14C]AA in male C3H mice and Fischer 344 (F344) rats after oral (40 and 150) mg/kg) or cutaneous (10 and 40 mg/kg) administration. Although these and other strains of rodents have been used frequently in toxicity studies of AA, results of pharmacokinetic studies are available for only the Sprague-Dawley rat. In the current study, C3H mice rapidly absorbed and metabolized orally administered AA, with about 80% of the dose exhaled as 14CO2 within 24 h. Excretion in urine and feces accounted for approximately 3% and 1% of the dose, respectively. Elimination of 14C from plasma, liver, and kidney was rapid but was slower from fat. The disposition of orally administered AA in F344 rats was similar to the results obtained from mice. After cutaneous administration to C3H mice, about 12% of the dose was absorbed, while the remainder apparently evaporated. Approximately 80% of the absorbed fraction of the dose was metabolized to 14CO2 within 24 h. Excretion in urine and feces each accounted for less than 0.5% of the dose. Elimination of radioactivity from plasma, liver, and kidney was rapid; however, levels in fat were higher at 72 h than at 1 or 8 h. After cutaneous administration to F344 rats, 19-26% of the dose was absorbed, and the rest apparently evaporated. Disposition of the absorbed fraction of the dose was similar to results found in mice. Results from an in vitro experiment with rat skin showed that at least 60% of the applied dose evaporated and about 25% was absorbed, confirming the in vivo results. High-performance liquid chromatography (HPLC) analysis of rat urine and rat and mouse tissues indicated that absorbed AA was rapidly metabolized by the beta-oxidation pathway of propionate catabolism. In summary, rapid detoxification of systemically absorbed AA, as observed here in C3H mice and F344 rats, can explain findings that AA causes minimal systemic toxicity despite its causing irritation at portal-of-entry tissues.

Acrylates↗
PubMed1987

[Plasma levels and tissue concentrations in rabbits following cutaneous administration of an indomethacin solution].

After cutaneous application to rabbits of a solution containing 1% of indomethacin (Elmetacin), concentration-time curves were determined in the skin-layers, in the subcutaneous tissue, in the superficial musculature, in the knee-joint capsule and in plasma. The quantitative assay used on-line fluorimetric detection after separation by HPLC and alkaline hydrolysis. Levels of indomethacin decreased with the depth of the tissue layers at the site of application. Indomethacin concentrations in the examined tissues exceeded plasma concentration at least twice for up to 8 h. Indomethacin was also detectable in the contralateral untreated tissue specimens and in the knee joint capsule.

Administration, Topical↗
PubMed1976

Reversal of experimental essential fatty acid deficiency by cutaneous administration of safflower oil.

The intriguing observation that cutaneous application of essential fatty acid (EFA)-rich oil corrects the biochemical abnormalities of EFA deficiency was evaluated in EFA-deficient rats. Approximately 185 mg of safflower oil (140 mg of linoleic acid) were applied daily for 15 days to the kin of EFA-deficient rats. Before and after treatment with the safflower oil, the fatty acid patterns of plasma and erythrocyte phospholipid as well as of plasma triglyceride and cholesterol ester fractions were determined. The linoleic and arachidonic acid content of both plasma and erythrocyte phospholipid increased, while the eicosatrienoic acid content of both fractions decreased. The linoleic acid content of plasma triglyceride increased with safflower oil treatment, but little change occurred in the almost undetectable pretreatment levels of arachidonic and eicosatrienoic acid. In the plasma cholesterol ester fraction, arachidonic acid increased with treatment and eicosatrienoic acid decreased, but the small increase in the linoleic acid content was not statistically significant. Thus, the study confirms the observation that cutaneous application of EFA-rich oils reverses the plasma biochemical manifestation of EFA deficiency. In addition cutaneously applied EFA-rich oils reversed the biochemical manifestations of EFA deficiency in erythrocytes. Whether or not cutaneous application of such oils will prevent EFA deficiency, however, remains to be proven.

Administration, Oral↗
PubMed1995

[Painless ESWL by cutaneous administration of Vaseline].

In a prospective clinical study we investigated how effective cutaneous Vaseline application was in pain reduction during ESWL. In 150 patients (group 1) Vaseline was applied on a skin area corresponding to the entry site of shockwaves directly before lithotripsy; in 75 patients (group 2) ESWL was performed without Vaseline. Analgesic sedation was needed by 10/150 (6.7%) in group 1 and 27/75 (36.4%) in group 2 (P < 0.001). The median pain score in group 1 was 2.5 +/- 1.05 and that in group 2 was 4.25 +/- 1.13 (P < 0.05). Local Vaseline application significantly reduces pain during ESWL independent of stone location. Most pain results from cavitation at the skin surface and is blocked by Vaseline. Cutaneous Vaseline application to reduce the need for analgesic sedation might be especially useful in outpatient ESWL procedures.

Procedural Sedation↗
PubMed1982

Lipoproteins during oral and cutaneous administration of oestradiol-17 beta to menopausal women.

Thirty-eight post-menopausal women were randomly allocated to substitution treatment with either oestradiol-17 beta orally (2-4 mg) or cutaneously (3 mg). The concentrations of cholesterol (C), triglycerides (TG) and phospholipids were determined in the high density lipoprotein (HDL)-, the low density lipoprotein (LDL)- and the very low density lipoprotein (VLDL)- fractions twice before medication and after 2, 4 and 6 months of treatment. Both treatments gave satisfactory clinical results. Oral doses increased the HDL and decreased the LDL thus raising the HDL-C/LDL-C ratio. The higher oral dose also increased the TG concentration. Cutaneous oestradiol gave only minimal changes of the lipoproteins. The lipoprotein changes observed during treatment with oral oestradiol might reduce the risk for atherosclerotic disease. Therefore, from a lipoprotein point of view, oral oestradiol treatment probably could be considered beneficial. The cutaneous oestradiol treatment had comparable clinical effects without any influence on the lipoprotein pattern.

Administration, Oral↗
PubMed1982

Oestrogens, gonadotrophins and SHBG during oral and cutaneous administration of oestradiol-17 beta to menopausal women.

Thirty-eight post-menopausal women were randomly allocated to 6 months of treatment with either 2-4 mg of micronized oestradiol-17 beta taken orally or 3 mg of oestradiol-17 beta applied cutaneously. The plasma concentrations of oestrone, oestradiol, LH, FSH and sex hormone binding globulin (SHBG) were determined twice before and after 2, 4 and 6 months of treatment. In both groups the clinical effects were satisfactory. During treatment the mean oestradiol levels showed similar increases in the two groups while the oestrone concentration was markedly raised only among those taking oestradiol orally. The mean LH and FSH concentrations were significantly lowered in both groups. SHBG was increased with both treatments although more marked in the group on oral medication. Doubling of the oral dose from 2 mg to 4 mg gave significant changes of the LH, FSH and oestrone concentrations. Thus, in the given doses, the two routes of administration seemed to have similar effects on post-menopausal symptoms and on the plasma concentrations of gonadotrophins and oestradiol. However the plasma oestrone and SHBG levels became significantly higher during the oral than during the cutaneous treatment.

Administration, Oral↗
PubMed1983

High density lipoprotein subfractions during oral and cutaneous administration of 17 beta-estradiol to menopausal women.

Thirty eight women with menopausal vasomotor symptoms were randomly allocated to 6 months treatment with either 2-4 mg micronized estradiol given orally or 3 mg estradiol applied cutaneously. The concentrations of cholesterol (C) and phospholipids (PL) were determined in high density lipoprotein (HDL) and its subfractions HDL2 and HDL3 twice before treatment and after 2, 4, and 6 months of medication. Oral estradiol increased the C and PL concentration in the HDL2 fraction in a dose-dependent way. With 2 mg estradiol orally the HDL3 fraction did not change, whereas 4 mg estradiol orally increased the C and PL concentrations in the HDL3 fraction. Cutaneous treatment with estradiol did not influence the lipid level in HDL or its subfractions. It is concluded that the rise of HDL during estrogen treatment is mainly caused by an elevation of the HDL2 fraction. Furthermore, the route of administration of estrogens has a profound influence on the metabolism of the HDL subfractions.

Administration, Oral↗