Further Studies to Support the Use of Coproporphyrin I and III as Novel Clinical Biomarkers for Evaluating the Potential for Organic Anion Transporting Polypeptide 1B1 and OATP1B3 Inhibition

Shen, Hong; Christopher, Lisa J.; Lai, Yurong; Gong, Jiachang; Kandoussi, Hamza; Garonzik, Samira M.; Perera, Vidya; Garimella, Tushar; Humphreys, W. Griffith

doi:10.1124/dmd.118.081125

Cited by 46 publications

(68 citation statements)

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“…The baseline AUC of CPI was also compared with data from five recently reported clinical studies (Lai et al, 2016;Kunze et al, 2018;Liu et al, 2018;Shen et al, 2018;Takehara et al, 2018). Mean baseline AUCs were comparable irrespective of gender or ethnicity of subjects, with a weighted mean AUC 0-24 of 18.9 nM×h (n 5 91, CV 24%) ( Table 2).…”

Section: Resultsmentioning

confidence: 99%

“…For the first time, an analogous approach was undertaken here for selected endogenous biomarkers (TDA, HDA, GCA, GDCA, TDCA, and CPIII) ( Table 1) and their utility was evaluated against rosuvastatin and CPI (or in combination with CPI). CPI was considered as a reference OATP1B biomarker based on interaction data published thus far and low inter-and intraindividual variability in its baseline T 0 and plasma concentrations over 24 hours, with no evident postprandial effect (Lai et al, 2016;Barnett et al, 2018;Kunze et al, 2018;Shen et al, 2018). In the current analysis, minor fluctuations in 24-hour baseline were observed for TDA and HDA, suggesting a possible food effect.…”

Section: Discussionmentioning

confidence: 99%

“…For example, a separate analysis was conducted for CPI using recently reported clinical EBI data to assess the variability of its plasma baseline AUC across several studies (data collated from 91 subjects in total). Due to limited availability of individual CPI data reported in those studies, the weighted baseline AUC from time 0 to 24 hours (AUC 0-24 ) and between-study variability were calculated from the mean CPI AUC data reported in five separate studies (Lai et al, 2016;Kunze et al, 2018;Liu et al, 2018;Shen et al, 2018;Takehara et al, 2018). Given that plasma data were only collected for 6 hours in Kunze et al 2018, the AUC for CPI was Fig.…”

Section: Methodsmentioning

confidence: 99%

“…biomarkers in the presence of OATP1B inhibitors; these studies have been done in preclinical species (Chu et al, 2015;Watanabe et al, 2015;Shen et al, 2016;Thakare et al, 2017) and in humans (Lai et al, 2016;Shen et al, 2017Shen et al, , 2018Takehara et al, 2017Takehara et al, , 2018Kunze et al, 2018;Liu et al, 2018). Selectivity, sensitivity, and minimal variability in the baseline condition need to be considered for evaluation of endogenous molecules as potential clinical biomarkers of transporter function in vivo (Chu et al, 2017;Chu et al, 2018;Müller et al, 2018;Rodrigues et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

“…The majority of the currently reported data for endogenous OATP1B biomarkers come from screening studies in healthy subjects following a single dose of rifampicin (Shen et al, 2017;Takehara et al, 2017Takehara et al, , 2018. Recently, a number of studies have monitored coproporphyrin I (CPI) following the administration of weak and moderate OATP1B inhibitors (Kunze et al, 2018;Liu et al, 2018;Shen et al, 2018). The reported studies focused on comparison of the plasma concentration-time area under the curve (AUC) or mean magnitude of DDI [ratio of the AUC (AUCR)] between one of the clinical probes (rosuvastatin, atorvastatin, and pravastatin) and CPI (Lai et al, 2016;Yee et al, 2016;Takehara et al, 2017Takehara et al, , 2018Kunze et al, 2018;Liu et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

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Comprehensive Evaluation of the Utility of 20 Endogenous Molecules as Biomarkers of OATP1B Inhibition Compared with Rosuvastatin and Coproporphyrin I

Barnett

Ogungbenro

Ménochet

et al. 2018

J Pharmacol Exp Ther

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Endogenous biomarkers can be clinically relevant tools for the assessment of transporter function in vivo and corresponding drug-drug interactions (DDIs). The aim of this study was to perform systematic evaluation of plasma data obtained for 20 endogenous molecules in the same healthy subjects (n 5 8-12) in the absence and presence of organic anion transporting polypeptide (OATP) inhibitor rifampicin (600 mg, single dose). The extent of rifampicin DDI magnitude [the ratio of the plasma concentration-time area under the curve (AUCR)], estimated fraction transported (f T), and baseline variability was compared across the biomarkers and relative to rosuvastatin and coproporphyrin I (CPI). Out of the 20 biomarkers investigated tetradecanedioate (TDA), hexadecanedioate (HDA), glycocholic acid, glycodeoxycholic acid (GDCA), taurodeoxycholic acid (TDCA), and coproporphyrin III (CPIII) showed the high AUCR (2.1-8.5) and f T (0.5-0.76) values, indicative of substantial OATP1Bmediated transport. A significant positive correlation was observed between the individual GDCA and TDCA AUCRs and the magnitude of rosuvastatin-rifampicin interaction. The CPI and CPIII AUCRs were significantly correlated, but no clear trend was established with the rosuvastatin AUCR. Moderate interindividual variability (15%-62%) in baseline exposure and AUCR was observed for TDA, HDA, and CPIII. In contrast, bile acids demonstrated high interindividual variability (69%-113%) and significant decreases in baseline plasma concentrations during the first 4 hours. This comprehensive analysis in the same individuals confirms that none of the biomarkers supersede CPI in the evaluation of OATP1Bmediated DDI risk. Monitoring of CPI and GDCA/TDCA may be beneficial for dual OATP1B/sodium-taurocholate cotransporting polypeptide inhibitors with consideration of challenges associated with large inter-and intraindividual variability observed for bile acids. Benefit of monitoring combined biomarkers (CPI, one bile acid and one fatty acid) needs to be confirmed with larger data sets and against multiple OATP1B clinical probes and perpetrators.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Comprehensive Evaluation of the Utility of 20 Endogenous Molecules as Biomarkers of OATP1B Inhibition Compared with Rosuvastatin and Coproporphyrin I

Barnett

Ogungbenro

Ménochet

et al. 2018

J Pharmacol Exp Ther

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Antitubercular Agents

Aldrich¹,

Wallis²,

Hegde³

et al. 2021

Burger's Medicinal Chemistry and Drug Discovery

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Mycobacterium tuberculosis remains the leading cause of death due to infection in humans. Although antibiotics are available to treat drug‐sensitive M. tuberculosis infections, the increasing incidence of drug‐resistant strains is threatening our ability to gain hold of this pandemic. In addition, recent research has highlighted that even the current standard of care antibiotics face multiple obstacles for reaching therapeutic concentrations at the site of infection. In this article, we detail the current standard of care for clinical tuberculosis (TB) disease, the chemistry, mechanisms of action, and mechanisms of resistance for the antibiotics used clinically to treat TB, the growing problem of antibiotic resistance, and other challenges associated with TB treatment, and host‐directed therapies as an additional approach to treatment. This article is meant to serve as the foundation to build from as the field addresses the dire need for continued development of new therapeutic strategies to treat TB.

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