11 research outputs found
Investigation of in vitro transdermal absorption of fentanyl from patches placed on skin samples obtained from various anatomic regions of dogs
Objective-To investigate in vitro transdermal absorption of fentanyl from patches through skin samples obtained from various anatomic regions of dogs. Sample Population-Skin samples from 5 Greyhounds. Procedure-Skin samples from the dogs' thoracic, neck, and groin regions were collected postmortem and frozen. After samples were thawed, circular sections were cut and placed in Franz-type diffusion cells in a water bath (32degreesC). A commercial fentanyl patch, attached to an acetate strip with a circular hole, was applied to each skin sample. Cellulose strips were used as control membranes. Samples of receptor fluid in the diffusion cells were collected at intervals for 48 hours, and fentanyl concentrations were analyzed by use of high-performance liquid chromatography. Results-Mean +/- SD release rate of fentanyl from the patch, defined by its absorption rate through the non-rate-limiting cellulose membrane, was linear during the first 8 hours (2.01 +/- 0.05 pg/cm(2) of cellulose membrane/h) and then decreased. Fentanyl passed through skin from the groin region at a faster rate and with a significantly shorter lag time, compared with findings in neck or thoracic skin samples. Conclusions and Clinical Relevance-In vitro, fentanyl from a patch was absorbed more quickly and to a greater extent through skin collected from the groin region of dogs, compared with skin samples from the thoracic and neck regions. Placement of fentanyl patches in the groin region of dogs may decrease the lag time to achieve analgesia perioperatively; however, in vivo studies are necessary to confirm these findings
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The role of serum and tissue pharmacology studies in the design and interpretation of chemoprevention trials.
The design and interpretation of chemoprevention trials are challenging tasks. Innovative methodological approaches to these investigations are in initial stages of development. Important pharmacologic issues should be addressed as early as possible in these trials to facilitate the optimal design of large, Phase III, randomized trials. These include determining the optimal dose of the compound and the toxicity profile. Other key areas involve the use of serum concentrations to monitor subject compliance, the evaluation of concentration of the chemopreventive agent in the target tissue, adequate assessment of the drug delivery systems, and the evaluation of the relationship between the dose administered and the serum or tissue concentrations achieved. Whenever possible the investigation of the relationship between serum or tissue concentrations of a chemopreventive agent vs its biologic activity should be determined. Specific examples involving the retinoids and carotenoids are presented