INVESTIGATION OF POLAR SURFACE AREA AS A NOVEL PARAMETER AFFECTING ORAL BIOAVAILABILITY OF DRUGS | ||||
| Bulletin of Pharmaceutical Sciences Assiut University | ||||
| Article 5, Volume 27, Issue 2, December 2004, Page 223-235 PDF (393.51 K) | ||||
| Document Type: Original Article | ||||
| DOI: 10.21608/bfsa.2004.65451 | ||||
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| Authors | ||||
| Mohammed A. Osman1; Gamal M. El Maghraby* 1; Mohsen A. Hedaya2 | ||||
| 1Department of Pharmaceutical Technology | ||||
| 2Department of Clinical Pharmacy, College of Pharmacy,Tanta University, Tanta, Egypt | ||||
| Abstract | ||||
| Fast and reliable prediction of intestinal absorption is a key factor in drug design. New parameters for this prediction have been introduced recently. These included the hydrogen bonding capacity and the polar surface area (PSA). High PSA accounted for poor oral absorption and vice versa. Here we are investigating the significance of PSA in intestinal absorption of a series of lipophilic steroidal model drugs. These included; Betamethason valerate (BMV), Betamethasone (BM), prednisone (PD) and methyltestosterone (MT), with PSA values of 100.9, 94.83, 91.67 and 37.3 Å, respectively. An in situ intestinal perfusion technique was employed using the rabbit as model animal. The study investigated drug absorption from the jejunoileum and ascending colon. The results revealed good absorption from both segments for all tested drugs except PD which was absorbed from the jejunoileum only. Poor correlation was evident between the absorptive clearance and the net water flux in both segments suggesting mainly a trans-cellular absorption of these compounds. The percentage fraction absorbed (%Fa) was in the order of BMV > MT > BM > PD with the later showing negligible absorption from the ascending colon. These results did not correlate with the calculated PSA values. Accordingly, the octanol/water partition coefficient (log P) was considered. The log P values were, 3.6, 3.36, 1.94 and 1.46 for BMV, MT, BM and PD, respectively. These values correlated with the %Fa values. However, it should be noted that the recorded colonic absorption is against expectation for such lipophilic drugs. In conclusion PSA failed to correlate with the oral absorption of the lipophilic steroids. Although log P correlated well with the absorption of these compounds especially with jejunoileum segment it is advisable not to rely on single factor for predicting oral bioavailability. | ||||
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