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Absorption of diazepam after its rectal administration in dogs
1995
Papich, M.G. | Alcorn, J.
A cross-over study was performed in 6 healthy mixed-breed dogs and 4 healthy Beagles. Diazepam was administered per rectum to Beagles (0.5 mg/kg of body weight) and mixed-breed dogs (2 mg/kg), and IV (0.5 mg/kg) to both groups of dogs. Each dog received the drug by both routes, with a 1-week washout period between dosages. After diazepam administration, blood samples were collected to measure plasma concentration of diazepam and its active metabolites, desmethyldiazepam and oxazepam, by use of reverse-phase high-performance liquid chromatography (HPLC). Systemic availability was assessed by comparing the area under the curve for diazepam metabolites for each route of administration. Mean (+/- SD) diazepam concentrations in plasma after rectal administration were low in comparison with those obtained after IV administration, with systemic availability of only 7.4 (+/- 5.9) and 2.7 (+/- 3.2)% for the high and low dose, respectively. However, diazepam was converted to its metabolites within minutes after administration. Accounting for the total concentration of benzodiazepines (diazepam plus desmethyldiazepam and oxazepam) in plasma, systemic availability was 79.9 (+/- 20.7) and 66.0 (+/- 23.8)% for the high and low dosage, respectively. After IV administration, diazepam concentration decreased, with a half-life of only 14 to 16 minutes, but desmethyldiazepam and oxazepam concentrations decreased more slowly, with a half-life of 2.2 to 2.8 hours and 3.5 to 5.1 hours, respectively. Each of the metabolites is reported to have anticonvulsant activity. After rectal administration of the high dose, mean total benzodiazepine concentration was above 1.0 micrograms/ml within 10 minutes and was maintained above this concentration for at least 6 hours. We conclude that diazepam is absorbed after rectal administration in dogs, and that the pharmacologic effects are probably caused by the active metabolites, not the parent drug. Samples also were analyzed by use of a nonspecific commercial benzodiazepine fluorescence polarization immunoassay (FPIA). Correlation between the FPLA and HPLC assay was strongest for diazeparn (R2 = 0.84), weak for desmethyldiazepam (R2 = 0.09), and nonexistent for oxazepam. We conclude from a comparison of assays that HPLC is preferred over the FPLA method for measuring benzodiazepines in dogs.
Показать больше [+] Меньше [-]Histologic evaluation of tissue reactivity and absorption in response to a new synthetic fluorescent pigmented polypropylene suture material in rats
1995
Beardsley, S.L. | Smeak, D.D. | Weisbrode, S.E.
The degree and type of tissue reactivity and the absorption of a new suture material was determined by implantation within rat gluteal muscles. Amount and type of tissue inflammatory reaction was compared among the new suture material, polypropylene, and coated polyamide. Histologic evaluation of the tissues in which sutures were implanted indicated that the new suture material, polypropylene, and coated polyamide had similar amounts and types of reaction at 30 days or less after implantation, but differed after 30 days. The new suture material and polypropylene had an inflammatory reaction zone measuring less than 25% of the high-power field after 60 days, but the coated polyamide still induced reaction greater than 45% of the field at 90 days. At 60 and 90 days after implantation, the new suture material and polypropylene induced a mature fibrous reaction; the reaction to coated polyamide was either immature fibrous or granulomatous, depending on whether there was rupture of the suture coat. There was no observable absorption of the new suture material at 90 days. This study indicated that the new suture material is nonabsorbable and is minimally reactive in rat muscle. The tissue reactions induced by this suture material are similar to those of polypropylene and significantly less than those induced by coated polyamide after 30 days following implantation.
Показать больше [+] Меньше [-]Effect of psyllium on plasma concentration of glucose, breath hydrogen concentration, and fecal composition in calves with diarrhea treated orally with electrolyte solutions
1995
Naylor, J.M. | Liebel, T.
We investigated the effect of adding psyllium to a standard electrolyte solution in 10 calves with diarrhea. The calves were tested with the standard solution on one day and standard solution plus psyllium on the alternate day. The order of treatments was randomized. Psyllium converted the solution into mucilage, but did not affect fecal consistency. Mean +/- SEM area under the glucose absorption curve was lower for mucilaginous than for nonmucilaginous solutions, 2.1 +/- 0.62 vs 3.75 +/- 1.18 mmol.h, respectively, but the difference was not significant. The area under the breath hydrogen curve was marginally lower for mucilaginous than nonmucilaginous solutions, 102 +/- 20 and 209 +/- 60 ppm.h, respectively. The usefulness of such decreased bacterial fermentation is doubtful.
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