The aim is to investigate the influence of the antidiabetic drug gliclazide on the ileal permeation of the semisynthetic bile acid, MKC, in tissues from healthy and diabetic rats. Sixteen Wistar rats (350 +/- 50 g) were randomly allocated into four groups (4 rats per group, 8 chambers per rat, i.e., n=32) two of which were made diabetic (given alloxan i.v. 30 mg/kg). Group 1 was used to measure the permeation of MKC (50 microg/ml) alone (control) while group 2 to measure MKC permeation in the presence of gliclazide (200 microg/ml). The diabetic groups 3 (gliclazide) and 4 (MKC+gliclazide) were treated in the same way. Rats were sacrificed and tissues were mounted into the Ussing chamber for the measurement of MKC mucosal to serosal (absorptive) and serosal to mucosal (secretory) fluxes. In healthy tissues, gliclazide reduced MKC absorptive flux (p < 0.01) and increased its secretory flux (p < 0.01). In diabetic tissues, gliclazide had no effect on either the absorptive or the secretory fluxes of MKC. The lack of effect of gliclazide on MKC permeation in diabetic tissues suggests the absence or suppressed drug transporters. Furthermore, gliclazide inhibition of MKC absorptive flux and induction of MKC secretory flux in healthy tissues may result from the selective inhibition of an efflux drug transporter.
Methacrylates serve as bases for acrylic resins which are used in prosthetics. Methyl methacrylate as a small molecular acrylate can permeate thin protective disposable gloves. Using adequate personal protective equipment, like nitrile rubber gloves, is the most important preventive measure in this occupation. Health practitioners should recognize possible occupational hazards in dentistry and implement appropriate preventive measures to protect health of workers.
The aim of ths study was to investigate the pharmacokinetics of cefotaxime sodium (CEF) pharmacokinetics after oral application in the form of sodium 3alpha,7alpha-dihydroxy-12-keto-5beta-cholanate (MKC) microvesicles (MV) in rat. Thirty Male Wister rats were divided into six groups (n=5 per group). Groups were treated orally with: (i) CEF (15 mg/kg) saline solution (15 mg/kg); (ii) CEF (15 mg/kg) saline solution with MKC (2 mg/kg); (iii) CEF saline solution mixed with blank microvesicles; (iv) CEF (15 mg/kg) encapsulated in microvesicles with saline solution; (v) CEF saline solution (15 mg/kg) mixed with blank MKC microvesicules; (vi) CEF (15 mg/kg) encapsulated in MKC microvesicules with saline solution. Data were analyzed using noncompartmental model. CEF oral bioavailability was increased twofold when coadministered with MKC and when encapsulated in microvesicles and ninefold when encapsulated in MKC microvesicles compared to the same CEF dose administered orally as saline solution. The increased bioavailability of CEF resulting from CEF encapsulation in microvesicules with MKC suggests that this formulation can extend the application of CEF from parenteral only to oral application.
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