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  • animal studies  (1)
  • bladder wall  (1)
  • 1
    Electronic Resource
    Electronic Resource
    Extensive Absorption of 2′,3′-Dideoxyinosine by Intratracheal Administration in Rats (1995)
    Springer
    Pharmaceutical research 12 (1995), S. 1901-1906 
    Details
    ISSN: 1573-904X
    Keywords: drug therapy ; AIDS ; intratracheal intubation ; biological availability ; animal studies ; 2′,3′-dideoxyinosine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. To evaluate the intratracheal route of administration as an alternative to oral administration for 2′,3′-dideoxyinosine (ddI). Methods. A ddI dose (40 mg/kg/300 µl or 6.5 mg/kg/50 µl) was instilled into the trachea in female Fisher rats and an intravenous tracer dose (9 µg/kg) of 3H-ddI was administered concomitantly to determine the drug clearance. Plasma concentrations were analyzed for the rate and extent of absorption. Results. ddI was rapidly absorbed from the lungs, with a bioavailability of 63% at 40 mg/kg and 101% at 6.5 mg/kg. By comparison, our previous data showed an oral bioavailability of about 15% (Pharm Res., 9:822, 1992). The distribution of a dye solution instilled intratracheally showed that a fraction of the 300 µL dose spilled over to the gastrointestinal tract, where the entire 50 µL dose was retained in the lungs. The different distribution of the two doses/volumes likely contributed to the different bioavailability, with a fraction of the higher dose/volume degraded in the gastrointestinal tract after the spillover. Absorption of ddI from the airspace of the lung was biexponential, suggesting two absorption processes. Conclusions. These data indicate significantly higher and less variable bioavailability of ddI by the intratracheal route of delivery compared to the oral route. Furthermore, the complete bioavailability at the lower dose/volume indicates no significant pulmonary first pass elimination for ddI.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1016283604540
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  • 2
    Electronic Resource
    Electronic Resource
    A Method to Study Drug Concentration–Depth Profiles in Tissues: Mitomycin C in Dog Bladder Wall (1991)
    Springer
    Pharmaceutical research 8 (1991), S. 168-173 
    Details
    ISSN: 1573-904X
    Keywords: tissue concentration profile ; bladder wall ; dog ; mitomycin C
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Determination of the depth of penetration of locally applied drug therapy and evaluation of possible mechanisms of drug transport require knowledge of drug concentration-versus-tissues depth profiles. A method to determine the drug concentration–depth profile is needed. We have devised such a method and used it to determine the penetration of mitomycin C (MMC) in the dog bladder wall after intravesical drug instillation. This method is based on sectioning of frozen tissue into 40-µm segments, followed by drug extraction and high-pressure liquid chromatography analysis. Tissue concentrations could be detected with a sensitivity of 1 ng/sample, or 20 ng/g for tissue samples of approximately 2 × 2 cm. This sensitivity was sufficient to describe the penetration of MMC in the bladder wall of dogs, using an identical instillation technique, dwell time, and MMC concentration as in human patients. Tissue concentrations were expressed relative to tissue weight or tissue protein contents. For MMC, standardization to tissue weight yielded a better mathematical fit of the concentration-versus-depth profiles than standardization to protein content. The time interval between tissue harvesting and freezing was critical. The MMC concentration at the urothelial side of dog bladders was 2- to 10-fold higher in samples processed immediately after harvesting, compared to samples processed after 1 hr or longer. This significant decrease was not due to drug metabolism in situ. In separate in vitro experiments, we found that the degradation of MMC in 8% tissue homogenate was relatively slow, with only a 30% decline in concentration over 24 hr. We speculate that the decrease in concentration was due to passive diffusion of MMC, away from the urothelial side. In summary, the present study demonstrates that determination of drug penetration into tissues in vivo is feasible.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1015827700904
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