In vitro binding and intrinsic elimination clearance for the model cationic drugs in a microsomal protein preparation (mean ± S.D., n = 4) No significant differences before and after treatment were found to exist for drug fraction unbound by microsomal protein, calculated microsomal association constant and internal elimination clearance for the three drugs (p > 0.05).
log Papp | pKa | Drug Fraction Unbound by Microsomal Protein | Microsomal Kb (ml-1 mg) | Microsomal CLint (ml min-1 g-1 liver) | |||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Control | Treatment | Control | Treatment | Control | Treatment | ||||||
| log Papp | pKa | ||||||||||
| Atenolol | 0.14 | 9.60 | 0.91 ± 0.06 | 0.91 ± 0.07 | 0.43 ± 0.09 | 0.46 ± 0.09 | 1.08 ± 0.35 | 1.11 ± 0.24 | |||
| Antipyrine | 0.33 | 1.45 | 1.00 ± 0.09 | 0.98 ± 0.07 | 0.61 ± 0.04 | 0.60 ± 0.06 | 0.75 ± 0.28 | 0.68 ± 0.13 | |||
| Propranolol | 3.10 | 9.45 | 0.49 ± 0.05 | 0.47 ± 0.02 | 5.93 ± 0.71 | 5.07 ± 0.89 | 9.44 ± 1.14 | 9.46 ± 0.73 | |||
log Papp, log octanol/water partition coefficient; pKa, negative logarithm of the ionization constant; microsomal Kb, calculated association constant for the microsomal protein preparation; microsomal CLint, intrinsic elimination clearance for the microsomal protein preparation.