These results suggest that direct bilirubin, GCDCA-S, and coproporphyrin I are promising surrogate probes for the quantitative assessment of potential OATP1B-mediated DDI.
The DDI study clarified the rate-determining processes of OATP/CYP3A substrates. Our analyses provide valuable information for predicting complex drug-drug interactions involving multiple processes.
Objective: To retrospectively investigate the effect of ward rounds to check swallowing function (hereafter, swallowing rounds) on the outcome of dysphagic patients. Methods: Upon requests from ward nurses or clinical departments in our hospital, a full-time certified nurse specialist in dysphagia examines the general condition of patients and performs screening for dysphagia. For patients who require detailed investigations, a transdisciplinary dysphagia care team conducts ward rounds and evaluates these patients in principle by videoendoscopic evaluation of swallowing. We reviewed the records of patients in whom swallowing rounds were conducted between September 2006 and March 2010, and analyzed the food texture and eating status scale (ESS) scores at the first intervention, after the first intervention and at the last observation; dysphagia severity scale (DSS) scores at the first intervention and at the last observation; and onset of pneumonia during intervention. Results: Among 1,330 patients suspected of dysphagia, 998 were judged to require detailed investigations and swallowing rounds were conducted. As a result of intervention, significant improvements in food texture, ESS score, and DSS score were observed. The incidence of pneumonia was 3.7%. Discussion: Improvements in food texture, ESS score, and DSS score were achieved by conducting swallowing rounds.
There was a miscalculation of coproporphyrin I AUC 0-24h in the published article (Volume 35, Number 7). After the correction of AUC 0-24h , AUC ratio and R-square were recalculated. Then, following corrections were made in the abstract, the body, Fig. 3, Fig. 4 and Table 2 in this article. The interpretation of data in this article was not influenced.The corrected sentences are below. Page 1. Abstract line 20: coproporphyrin I (r 2 = 0.78). line 23: (r 2 = 0.48-0.70).
Page 5.Effect of Rifampicin on the Plasma Concentrations of Coproporphyrin I. line 4: 2.3-and 3.5-times higher.Correlations between the AUC 0-24h of Endogenous OATP1B Substrates, and of these with the AUC 0-24h of Atorvastatin. line 6: coproporphyrin I (r 2 = 0.78). line 8: atorvastatin (r 2 of 0.65, 0.70 and 0.48, respectively).Issey Takehara and Takashi Yoshikado contributed equally to this work.The online version of the original article can be found at https://doi.org/10.
To identify oral drugs that likely display nonlinear pharmacokinetics due to saturable metabolism by intestinal CYP3A, our previous report using CYP3A substrate drugs proposed an approach using thresholds for the linear index number (LIN3A ¼ dose/K m ; K m , Michaelis-Menten constant for CYP3A) and the intestinal availability (F a F g ). Here, we aimed to extend the validity of the previous approach using both CYP3A substrate and non-substrate drugs and to devise a decision tree suited for early drug candidates using in vitro metabolic intrinsic clearance (CL int, vitro ) instead of F a F g . Out of 152 oral drugs (including 136 drugs approved in Japan, US or both), type I nonlinearity (in which systemic drug exposure increases in a more than dose-proportional manner) was noted with 82 drugs (54%), among which 58 drugs were identified as CYP3A substrates based on public information. Based on practical feasibility, 41 drugs were selected from CYP3A substrates and subjected to in-house metabolic assessment. The results were used to determine the thresholds for CL int, vitro (0.45 mL/min/pmol CYP3A4) and LIN3A (1.0 L). For four drugs incorrectly predicted, potential mechanisms were looked up. Overall, our proposed decision tree may aid in the identification of early drug candidates with intestinal CYP3Aderived type I nonlinearity.
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