SLCO2B1 (Solute Carrier Organic Anion Transporter Family Member 2B1)

Conclusion Both extrinsic factors (tumor-associated bacterial communities, tumor immune contexture and air pollution) and intrinsic factors predict EC recurrence. The complexity of tumor and host factors influencing cancer relapses underscore the need for more individualized prediction models of disease outcomes.

PBPK model simulations predicted no major change in rosuvastatin, a substrate for OATPs and BCRP, pharmacokinetics when co-administered with dicloxacillin or flucloxacillin. Simulations with dicloxacillin and P-gp substrates dabigatran or digoxin also predicted limited inhibition of P-gp transport.

The review also highlights the pharmacokinetic implications of, e.g., tacrolimus, digoxin, and metformin. Potential therapeutic interventions are also covered (diet, pre-/probiotics, fecal microbiota transplantation, modulation of PXR/FXR/AhR pathways). Considering the microbiota as a "second genome" enables more accurate prediction of drug exposure, reduction in toxicity, and optimization of dosing for orally administered preparations.

The phenotypic alterations in Oatp2b1-deficient mice occurred without substantial changes in measures of systemic exposure to the parent drug, SN-38, or its glucuronide conjugate. Collectively, our study indicates that plasma concentrations of SN-38 are a poor predictive biomarker of CPT-11-induced gastrointestinal toxicity and provides an incentive for the future development of intervention strategies aimed at increasing the tolerance to this clinically important drug with the use of OATP2B1 inhibitors.

Genetic variation in SULT2A1 may be useful to inform personalized dosing of abiraterone. ClinicalTrials.gov Identifier: NCT01949337.

PBPK model simulations predicted no major change in rosuvastatin, a substrate for OATPs and BCRP, pharmacokinetics, when co-administered with dicloxacillin or flucloxacillin. Simulations with dicloxacillin and P-gp substrates dabigatran or digoxin also predicted limited inhibition of P-gp transport.

Our study suggests a prognostic impact of statin use in the PFS in patients receiving abiraterone or enzalutamide for mCRPC. This may be related to the enhancement of the antitumor activity of the ADT drugs, but also to the cardioprotective effects associated with statin use.

At low concentrations, E23G and E23S17βG are selectively transported by OATP2B1 and OATP1B1, respectively. The findings in this study unveil the underlying molecular mechanisms for the hepatic disposition of estradiol glucuronides E23G and E23S17βG.

None of the selected food additives showed any effect on sulfasalazine permeability. These results suggest that the selected food additives are inhibitors of the studied transporters but are unlikely to cause clinically significant intestinal transporter-mediated drug interactions.

In HCC patients, the downregulation of SLCO1B1, SLCO1B3, and SLCO2B1 expression has been observed. SLCO genes such as SLCO1B1, SLCO1B3, and SLCO2B1 expression levels may also serve as prognostic predictive markers in HCC patients.

The bile acids accumulated by liver injury inhibited the uptake of BG by OATPs, especially that by OATP2B1. Hepatic impairment reduced BG hydrolysis by intestinal microflora and inhibited its transporter-mediated biliary excretion, which synergistically led to the attenuation of the enterohepatic circulation of BG, which altered its pharmacokinetics.

The inhibition of OATP1B1 and OATP2B1 was studied in vitro and by molecular docking to get an insight on the possible location and mode of binding of these HQ derivatives. Except for the homoproline derivative, the amino acid conjugates were found to be weak inhibitors of these transporters.