Aim: To quantitatively evaluate in vivo first-pass intestinal extraction of omeprazole and to investigate the possible involvement of cytochrome P450 3A4 (CYP3A4) and P-glycoprotein (P-gp) in this process in rabbits. Methods: Pharmacokinetic parameters were examined after intraduodenal (id), intraportal venous (ipv), and intravenous (iv) administration of omeprazole at various doses to intestinal and vascular access-ported rabbits. Extraction ratios in the liver and intestinal tract were determined from the area under the plasma concentration-time curve (AUC). In addition, omeprazole was administered by id or iv to rabbits alone or 30 min after the id administration of CYP3A4 or P-gp inhibitors (ketoconazole or verapamil, respectively). Results: Pharmacokinetic parameters of omeprazole were dose-dependent after id, ipv, and iv administration at various doses. After id administration of 3 mg/kg omeprazole, the hepatic and intestinal extraction ratio was 57.18%±2.73% and 54.94%±1.85%, while the value was 59.29%±3.14% and 54.20%±1.53% after given 6 mg/kg, respectively. Compared with the control group, the presence of ketoconazole (60 mg/kg) or verapamil (9 mg/kg) significantly increased the area under the plasma concentration time curve (AUC) and the peak concentration (C max ) of id-administered omeprazole, while it had no significant effect on omeprazole administered by iv. Conclusion: Oral omeprazole undergoes marked extraction in the small intestine, and increased bioavailability of the drug after id administration of ketoconazole and verapamil suggests that this increase results from inhibition of CYP3A4 and P-gp function in the intestine rather than the liver.

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Increased intestinal permeability induced by diclofenac can be attenuated by rebamipide, which partially contributed to the protection of mitochondrial function.

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Under the flight maneuvering of an aircraft, the maneuvering load on the rotor is generated, which may induce the change of dynamic behavior of aeroengine rotor system. To study the influence on the rotor dynamic behavior of constant maneuvering overload, a nonlinear dynamic model of bearing-rotor system under arbitrary maneuver flight conditions is presented by finite element method. The numerical integral method is used to investigate the dynamic characteristics of the rotor model under constant maneuvering overload, and the simulation results are verified by experimental works. Based on this, the dynamic characteristics of a complex intermediate bearing-squeeze film dampers- (SFD-) rotor system during maneuvering flight are analyzed. The simulation results indicate that the subharmonic components are amplified under constant maneuvering overload. The amplitude of the combined frequency components induced by the coupling of the inner and outer rotors is weakened. The static displacements of the rotor caused by the additional excitation force are observed. Besides, the period stability of the movement of the rotor deteriorates during maneuver flight. The design of counterrotation of the inner and outer rotors can effectively reduce the amplitude of subharmonic under constant maneuvering overload.