Background: We analyzed the pharmacokinetic-pharmacodynamic relationship of vancomycin to determine the drug exposure parameters that correlate with the efficacy and nephrotoxicity of vancomycin in patients with methicillin-resistant Staphylococcus aureus pneumonia and evaluated the need to use peak concentration in therapeutic drug monitoring (TDM). Methods: Serum drug concentrations of 31 hospitalized patients treated with vancomycin for methicillin-resistant S. aureus pneumonia were collected. Results: Significant differences in trough concentration (C_min)/minimum inhibitory concentration (MIC) and area under the serum concentration-time curve (AUC_0–24)/MIC were observed between the response and non-response groups. Significant differences in C_min and AUC_0–24 were observed between the nephrotoxicity and non-nephrotoxicity groups. Receiver operating characteristic curves revealed high predictive values of C_min/MIC and AUC_0–24/MIC for efficacy and of C_min and AUC_0–24 for safety of vancomycin. Conclusions: These results suggest little need to use peak concentration in vancomycin TDM because C_min/MIC and C_min are sufficient to predict the efficacy and safety of vancomycin.

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To identify the active components in Mori Cortex (Chinese medicine), Mori Cortex extracts were administered orally to rats, and then blood plasma, urine, and bile were analyzed. The results showed only a few remaining metabolites of mulberroside A. Consequently, to clarify the transitional properties of mulberroside A derivatives to tissues and the in vivo abundance ratio of mulberroside A compounds, the pharmacokinetics of mulberroside A derivatives were investigated in this study. When Mori Cortex extracts were administered orally, mulberroside A was only detected in small quantities in the plasma, and its bioavailability was about 1%. This is due to the first pass effect, by which most mulberroside A was converted into oxyresveratrol and transported into the circulating blood, and its absorption ratio was estimated at about 50%. Oxyresveratrol was found to be transported to tissues at high rates. As a result, when analyzing the pharmacological activity of the Mori Cortex in vitro, it is more useful to study oxyresveratrol than mulberroside A.

Several studies have shown that renal failure decreases CYP3A activity and that uremic toxins may play a role via transcriptional or translational modifications of cytochrome P450 (P450) enzymes and direct inhibition of P450-mediated metabolism. In this study, we evaluated the relationship between CYP3A activity (using plasma concentration of 4b-hydroxycholesterol as a biomarker) and clinical characteristics including plasma concentrations of indoxyl sulfate (3-INDS) and indole-3-acetic acid (3-IAA) in stable kidney transplant recipients. Forty-five Japanese kidney transplant recipients who underwent transplantation more than 90 days prior to the study were included. Morning blood samples were collected and plasma concentrations of 4b-hydroxycholesterol, 3-INDS, and 3-IAA were measured. Plasma concentrations of 4b-hydroxycholesterol were 57.1 6 11.2, 42.1 6 11.8, and 34.5 6 7.3 ng/ml in recipients with CYP3A5*1/*1 (n = 5), *1/*3 (n = 15), and *3/*3 (n = 25) genotypes, respectively, with significant differences between three genotypes. A significant correlation was observed between plasma concentrations of 4b-hydroxycholesterol and 3-INDS but not 3-IAA. Multiple regression analysis identified the number of CYP3A5*3 alleles in genotype, plasma concentration of 3-INDS, and body weight as independent variables associated with plasma concentration of 4b-hydroxycholesterol. In conclusion, these results suggest that CYP3A5 polymorphism and plasma concentration of 3-INDS may account for the interindividual variability of CYP3A activity, and that plasma concentration of 3-INDS may partially explain the gap in CYP3A activity that cannot be explained by genetic contribution in patients with renal failure.

A novel stilbene glucoside was isolated from the root bark of Morus alba L. (Moraceae), along with mulberroside A, cis-mulberroside A, oxyresveratrol. The structure of the novel stilbene glucoside was determined as oxyresveratrol 3'-O-beta-glucopyranoside.