Nao Setoguchi

Transient inhibition of CYP3A in rats by star fruit juice

Star fruit juice is a potent in vitro inhibitor of CYP3A; however, few reports are available on the inhibition of CYP3A activities by star fruit juice in vivo. Therefore, in this study, we investigated the CYP3A-mediated star fruit-drug interaction in vivo. The effect of star fruit juice on carbamazepine pharmacokinetics was examined in rats. In comparison with water, the area under the concentration-time curve (AUC) of carbamazepine was approximately 1.3-fold greater when star fruit juice (2 ml) was orally administered 1 h before the oral administration of carbamazepine (50 mg/kg). In contrast, the elimination half-life of carbamazepine and the AUC ratio of carbamazepine 10,11-epoxide to carbamazepine were not altered by the administration of star fruit juice. These results suggest that star fruit juice impairs the function of enteric CYP3A, but not of hepatic CYP3A. In addition, we evaluated the time course of recovery of CYP3A activity that was reduced after the treatment with star fruit juice. The inhibition by star fruit juice was recovered within approximately 24 h. These data suggest that the effect of star fruit juice is mainly reversible and transient. Thus, we discovered that star fruit juice alters the carbamazepine pharmacokinetics in rats.

An Advanced Objective Structured Clinical Examination Using Patient Simulators to Evaluate Pharmacy Students’ Skills in Physical Assessment

Objective. To implement an advanced objective structured clinical examination (OSCE) in the curriculum and to evaluate Japanese pharmacy students’ skills in physical assessment such as measuring pulse and blood pressure, and assessing heart, lung, and intestinal sounds. Design. An advanced OSCE was implemented in a hospital pharmacy seminar as a compulsory subject. We programmed patient simulators with 21 different patient cases in which normal and abnormal physiological conditions were produced. The virtual patients were then used to evaluate the physical assessment skills of fifth-year pharmacy students. Assessment. Significant differences were observed between the average of all the detailed evaluations and the mean results for the following skills: pulse measurement, blood pressure measurement, deflating the cuff at a rate of 2-3 mmHg/sec, listening to heart sounds, and listening to lung sounds. Conclusion. Administering an advanced OSCE using virtual patients was an effective way of assessing pharmacy students’ skills in a realistic setting. Several areas in which pharmacy students require further training were identified.

Change in Drug Concentration in Serum Stored in Sterilized Vacuum Tubes for Serum Separation

We investigated the change in drug concentrations in serum stored in sterilized vacuum tubes for serum separation. The serum concentrations of seven drugs-phenytoin, phenobarbital, carbamazepine, vancomycin, valproate, theophylline and digoxin-were determined after storage in three different vacuum tubes-Vacutainer® SST and SST II (SST, SST II, Becton Dickinson Co. Ltd.) and Neo-Tube® GP-SP 1029 (GP-SP, Nipro Co.). Though there was no change in the serum drug concentrations for any of the tested drugs in GP-SP, the concentrations of phenytoin, phenobarbital and carbamazepine in the serum stored in SST and SST II were significantly decreased due to adsorption onto the serum separator. The degree of adsorption was greater for the SST tube than the SST II tube and for the drugs, the order of adsorption was phenytoin>carbamazepine>phenobarbital. The adsorption of phenytoin onto the separator of SST depended on several storage conditions, such as initial drug concentration, storage temperature and storage volume, while its adsorption onto the SST II separator depended on storage temperature and storage volume. In addition, the change in phenytoin concentration during storage in the SST tube was well correlated with the free fraction of the drug. This indicates that protein binding is an important factor affecting the stability of drug concentrations in serum stored in separation tubes. Overall, the results of our study indicate that for accurate therapeutic drug monitoring, it is necessary to select vacuum serum separation tubes on the basis of drug concentration stability data for them.