[Download] "Suramin Pharmacokinetics After Regional or Systemic Administration" by Leijun Hu " eBook PDF Kindle ePub Free
eBook details
- Title: Suramin Pharmacokinetics After Regional or Systemic Administration
- Author : Leijun Hu
- Release Date : January 18, 2013
- Genre: Medical,Books,Professional & Technical,
- Pages : * pages
- Size : 15770 KB
Description
Suramin as chemosensitizer is concentration dependent, where tissue concentration might be more critical than plasma concentration. The present thesis investigated suramin tissue distribution in bladder wall and other important organs after regional or systemic administration. Although suramin is a highly hydrophilic compound, its penetration through urothelium and W1/2 are comparable with many other relatively more lipophilic drugs, such as doxorubicin. No drug-drug interaction was found between Mitomycin C and suramin in regard to the bladder wall penetration ability. Possible dose-dependent suramin penetration through the urothelium was observed, where suramin at higher concentration (20 mg/ml) can pass through the urothelium more easily than at low concentration (6 mg/ml). This phenomenon makes the prediction of suramin concentration in bladder wall difficult. Further experiments exploring suramin penetration at other dose levels might help the tissue concentration prediction. The distributed model successfully described the suramin concentration profiles in the bladder wall. The bladder wall distribution of fluorescent compound, however, reveals that the assumption of the distributed model for bladder is not valid, where bladder wall can only be considered a well capillary perfused tissue in lamina propria. After systemic administration, suramin retains in multiple tissues which might determines its long terminal half-life in plasma. Suramin distribution in several organs is likely dose dependent, predominantly in kidney. In order to correctly predict suramin tissue concentration after systemic administration, a whole body PBPK model was developed. Three local models, considering saturable tissue binding, rate-limiting membrane transport, with or without deep tissue binding pool, were tested and used for appropriate organs. The final model not only correctly depicted experimentally obtained tissue concentration and plasma concentration data but also successfully predicted plasma concentration profiles in human patients who received systemic single or split dose(s) of suramin.
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