Organic anion transporting polypeptide 2B1 (OATP2B1) is a widely expressed membrane transporter with diverse substrate specificity. In vitro and clinical studies suggest a role for intestinal OATP2B1 in the oral absorption of medications. Moreover, OATP2B1 is highly expressed in hepatocytes where it is thought to promote liver drug clearance. However, until now, a shortcoming of studies implicating OATP2B1 in drug disposition has been a lack of in vivo models. Here, we report the development of a knockout (KO) mouse model with targeted, global disruption of the Slco2b1 gene to examine the disposition of two confirmed mOATP2B1 substrates, namely, fexofenadine and rosuvastatin. The plasma pharmacokinetics of intravenously administered fexofenadine was not different between KO and wildtype (WT) mice. However, after oral fexofenadine administration, KO mice had 70% and 41% lower maximal plasma concentration (C max) and area under the plasma concentration-time curve (AUC 0-last) than WT mice, respectively. In WT mice, coadministration of fexofenadine with grapefruit juice (GFJ) or apple juice (AJ) was associated with reduced C max by 80% and 88%, respectively, while the AUC 0-last values were lower by 35% and 70%, respectively. In KO mice, AJ coadministration reduced oral fexofenadine C max and AUC 0-last values by 67% and 59%, respectively, while GFJ had no effects. Intravenous and oral rosuvastatin pharmacokinetics were similar among WT and KO mice. We conclude that intestinal OATP2B1 is a determinant of oral fexofenadine absorption, as well as a target for fruit juice interactions. OATP2B1 does not significantly influence rosuvastatin disposition in mice. SIGNIFICANCE STATEMENT A novel mouse model with targeted disruption of the Slco2b1 gene revealed that OATP2B1 is a determinant of oral absorption but not systemic disposition of fexofenadine, as well as a target of fruit juice interactions. Rosuvastatin oral and intravenous pharmacokinetics were not dependent on OATP2B1. These findings support the utility of the Slco2b1 KO mouse model for defining mechanisms of drug disposition at the intersection of in vitro and clinical pharmacology.

There is little known about the impact of nonalcoholic fatty liver disease (NAFLD) on drug metabolism and transport. We examined the pharmacokinetics of oral apixaban (2.5 mg) and rosuvastatin (5 mg) when administered simultaneously in subjects with magnetic resonance imaging-confirmed NAFLD ( = 22) and healthy control subjects ( = 12). The area under the concentration-time curve to the last sampling time (AUC) values for apixaban were not different between control and NAFLD subjects (671 and 545 ng/ml × hour, respectively; = 0.15). Similarly, the AUC values for rosuvastatin did not differ between the control and NAFLD groups (25.4 and 20.1 ng/ml × hour, respectively; = 0.28). Furthermore, hepatic fibrosis in NAFLD subjects was not associated with differences in apixaban or rosuvastatin pharmacokinetics. Decreased systemic exposures for both apixaban and rosuvastatin were associated with increased body weight ( < 0.001 and < 0.05, respectively). In multivariable linear regression analyses, only participant weight but not NAFLD, age, or // genotypes, was associated with apixaban and rosuvastatin AUC ( < 0.001 and = 0.06, respectively). NAFLD does not appear to affect the pharmacokinetics of apixaban or rosuvastatin.

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PURPOSE: The Cannabis Consultation Service (CCS) is an innovative pharmacist-led resource at the Sunnybrook Odette Cancer Centre. Its mandate is to provide education and guide patients through access and appropriate use of high-quality plant-derived cannabinoids (PDCs). Our objective was to describe the CCS, explain its processes, and characterize patient disposition with respect to use of PDCs. METHODS: We retrospectively reviewed the charts of patients referred to the CCS from July 13, 2020, to March 05, 2021. We used descriptive statistics to report on the patient population and service metrics. RESULTS: During the 34-week period, 96 patients accessed the CCS (median age, 61 years). The top reasons for CCS consultation were management of cancer pain, insomnia, and general interest. Medical cannabis was supported as an option in 44/96 patients. Reasons for not supporting PDC use included lack of indication, potential drug interaction/contraindication, or requiring treatment with first-line therapy. Of the 40 patients requiring a medical document, 22 initiated therapy. The most common product used was a 2:50 THC:CBD (Tetrahydrocannabinol:Cannabidiol) cannabis oil. At the date of last contact, few patients remained on therapy because of lack of benefit, patient choice, and/or hesitancy. CONCLUSION: Despite patients with cancer having interest in seeking PDCs for symptom management, only a few initiated and continued therapy. Pharmacists have an opportunity to advise patients and the oncology team on the risks and benefits of PDCs. These results can be used to support the development of medical cannabis programs by oncology centers and focus future research priorities.

Introduction: During the COVID-19 pandemic, clinical sites have closed their doors to student placements, leading to the implementation of remote rotations. The purpose was to determine best practices for distance preceptorship from the student’s perspective. Methods: A survey was sent to the pharmacy students at the Leslie Dan Faculty of Pharmacy who have completed at least one remote rotation. Results: Forty-eight out of 121 students (39%) completed the survey. It was found that 83% of the students were motivated during the start of their rotations, while 48% remained motivated throughout. Students who remained motivated had clear expectations set from the beginning, felt comfortable communicating issues regarding their assigned work with their preceptor, had similar rapport with remote preceptors as with in-person preceptors, had a preceptor who is always available for questions, and had a work environment free of distractions. Discussion:There are numerous best practices students and preceptors can utilise during a remote rotation to help students remain motivated. Preceptors and students should work together so that students remain motivated throughout their rotation. Setting expectations, having good communication, getting to know their preceptor, and having a work environment free of distractions are key factors for conducting a remote rotation.