Organic
anion-transporting polypeptide (OATP) 1A2 and OATP2B1 mediate
the intestinal absorption of drugs. This study aimed to identify fruit
juices or fruit juice components that inhibit OATPs and assess the
risk of associated food–drug interactions. Inhibitory potency
was assessed by examining the uptake of [3H]estrone 3-sulfate
and [3H]fexofenadine into HEK293 cells expressing OATP1A2
or OATP2B1. In vivo experiments were conducted using
mice to evaluate the effects of cranberry juice on the pharmacokinetics
of orally administered fexofenadine. Of eight examined fruit juices,
cranberry juice inhibited the functions of both OATPs most potently.
Avicularin, a component of cranberry juice, was identified as a novel
OATP inhibitor. It exhibited IC50 values of 9.0 and 37
μM for the inhibition of estrone 3-sulfate uptake mediated by
OATP1A2 and OATP2B1, respectively. A pharmacokinetic experiment revealed
that fexofenadine exposure was significantly reduced (by 50%) by cranberry
juice. Cranberry juice may cause drug interactions with OATP substrates.
Background
Irinotecan (CPT-11) is clinically known to cause severe diarrhea and gastrointestinal damage. Recently, we have reported that CPT-11-induced gastrointestinal damage is associated with the upregulation of intestinal P-glycoprotein (P-gp) expression and decreased absorption of its substrate, dabigatran etexilate (DABE), using a rat model. However, the P-gp activity or its contribution to the decreased absorption remains unclear. The aim of this study was to quantitatively evaluate how P-gp activity changes in rats with CPT-11-induced gastrointestinal damage, as assessed by the absorption of digoxin (DGX), a typical P-gp substrate.
Methods
Male Sprague-Dawley rats were intravenously administered CPT-11 at a dose of 60 mg/kg/day for 4 days to induce gastrointestinal damage. Then, the rats were administered DGX orally (40 μg/kg), after some of them were orally administered clarithromycin (CAM; 10 mg/kg), a P-gp inhibitor. DGX (30 μg/kg) was administered intravenously to determine the bioavailability (BA). The rats’ DGX plasma concentration profiles were determined using LC-MS/MS.
Results
CPT-11 treatment decreased the maximum concentration (Cmax) and area under the plasma concentration-time curve (AUCpo) of DGX, which does not contradict to the DABE study. Although in the CPT-11-treated group the BA of DGX was significantly decreased to 40% of the control value, CAM did not affect the BA of DGX in the CPT-11-treated group.
Conclusions
Increased P-gp expression in rats with CPT-11-induced gastrointestinal damage is not necessarily associated with increased P-gp activity or contribution to the drug absorption in vivo. The decreased DGX absorption observed in this study might be attributable to other factors, such as a reduction in the absorptive surface area of the gastrointestinal tract.
Introduction This study aimed to evaluate the participants’ comfort in understanding research papers written in English and discussing such research in English via an Asian online journal club. Methods A self-administered online survey was delivered to seven journal club meeting attendees from July 2020 to July 2021. A customer satisfaction analysis was performed to assess the association between the participants’ perspectives on program logistics and satisfaction. Results The recovery rate was 37.0% (44/119). After participating in the journal club, the median scores of critical appraisal skills, knowledge and/or pharmaceutical care skills in clinical practice, and discussion skills in English (assessed using a seven-point Likert scale) improved significantly (compared to pre-participation median scores) from 4 (interquartile range [IQR]: 3–5) to 5 (IQR: 4–6), 5 (IQR: 4–5) to 5 (IQR: 5–6), and 4 (IQR: 2–5) to 5 (IQR: 3–5), respectively ( P < 0.0001). The respondents also expressed great appreciation for the benefits and overall qualities of the journal club. Additionally, regarding patient care behavior after participation in the journal club, 34 (77.3%), 17 (38.6%), 16 (36.4%), and 14 (31.8%) respondents reported improvement in “drug information services,” “patient assessments,” “patient counseling,” and “multidisciplinary rounds,” respectively. Customer satisfaction analysis revealed that sharing information, mutual discussion, a shift system of presenters and co-chairs, and session duration should be improved as a matter of highest priority. Conclusion The findings suggest that our program could be helpful for Asian pharmacists, pharmacy students, and faculty members of the department of pharmacy.
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