No abstract

In adult patients after living‐donor liver transplantation, postoperative days and the cytochrome P450 3A5 (CYP3A5) genotype are known to affect tacrolimus pharmacokinetics. In this study, we constructed a physiologically‐based pharmacokinetic model adapted to the clinical data and evaluated the contribution of liver regeneration as well as hepatic and intestine CYP 3A5 genotypes on tacrolimus pharmacokinetics. As a result, liver function recovered immediately and affected the total body clearance of tacrolimus only during a limited period after living‐donor liver transplantation . The clearance was about 1.35‐fold higher in the recipients who had a liver with the CYP 3A5*1 allele than in those with the CYP 3A5*3/*3 genotype, whereas bioavailability was ~0.7‐fold higher in the recipients who had intestines with the CYP3A5*1 allele than those with CYP 3A5*3/*3 . In conclusion, the constructed physiologically‐based pharmacokinetic model clarified that the oral clearance of tacrolimus was affected by the CYP 3A5 genotypes in both the liver and intestine to the same extent.

No abstract

Vancomycin (VCM) is a first-line antibiotic used for methicillin-resistant Staphylococcus aureus (MRSA), and therapeutic drug monitoring (TDM) is recommended to minimize the risk of nephrotoxicity and ensure successful therapeutic outcomes. In Kyoto University Hospital, we have developed a new approach of pharmacist intervention in the medication with VCM, which is named "Protocol-Based Pharmacotherapy Management (PBPM)." PBPM is based on a protocol approved in a hospital committee, which mentioned that pharmacists could order TDM and propose the most appropriate treatment plans with VCM to surgeons. From April 2011 to September 2014 in Kyoto University Hospital, a total of 54 patients hospitalized for cardiovascular surgeries received VCM without the treatment of hemodialysis. Twenty-nine patients before introducing PBPM were the control group. The VCM treatment according to PBPM was applied to 25 patients (protocol group). The incidence of acute kidney injury (AKI) due to VCM therapy, the retention rates of VCM blood concentration maintained in the therapeutic range (10-20 µg/mL) and in the toxic range (over 20 µg/mL) were retrospectively surveyed. The incidence of AKI was significantly lower in the protocol group than that in the control group (8.0％ vs 31.0％, P < 0.05). The retention rates maintained in the therapeutic blood concentration range and in the toxic blood concentration range were significantly different between the control group and the protocol group. These results demonstrate that pharmaceutical intervention based on PBPM for MRSA treatment is effective for maintaining VCM blood concentration in the therapeutic range, resulting in a reduction of adverse drug reactions.