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Recovery of OATP1B Activity after Living Kidney Transplantation in Patients with End-Stage Renal Disease

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Abstract

Purpose

Recently, several studies have shown that renal failure decreases the metabolic clearance of drugs and the transportation capability of some drug transporters. However, whether organic anion transporting polypeptide (OATP)1B activities decrease in renal failure remains unknown. In this study, we measured plasma concentrations of coproporphyrin-I (CP-I), a specific endogenous OATP1B probe, in patients with end stage renal disease before and after living kidney transplantation and evaluated the effect of renal function on OATP1B activity.

Methods

This prospective study recruited 13 patients with end-stage renal disease. Plasma CP-I concentrations were measured before and 7, 14, 30 and 90 days after living kidney transplantation.

Results

Plasma CP-I concentrations decreased over time after living kidney transplantation and showed significant difference on day 90 compared with before living kidney transplantation [1.12 ± 0.59 vs 0.65 ± 0.27 ng/mL, p < 0.05 (95% CI of difference − 0.927, −0.013)]. A significant negative correlation was observed between estimated glomerular filtration rate and plasma CP-I concentration (r = −0.30, p < 0.05), suggesting recovery of OATP1B activity with improvement in renal function.

Conclusions

OATP1B activity may decrease in renal failure and dose adjustment of OATP1B substrates may be needed in patients with renal failure.

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Abbreviations

ABCG2:

ATP-binding cassette sub-family G member 2

ALT:

alanine aminotransaminase

CKD-EPI:

Chronic Kidney Disease Epidemiology Collaboration

CMPF:

3-carboxy-4-methyl-5-propyl-2-furan-propanoic acid

CP:

coproporphyrin

eGFR:

estimated glomerular filtration rate

EMA:

European Medicines Agency

FDA:

Food and Drug Administration

HMG:

hydroxymethylglutaryl

HSA:

human serum albumin

LLOQ:

lower limit of quantification

MRM:

multiple reaction monitoring

MRP:

multidrug resistance-associated protein

OATP:

organic anion transporting polypeptides

PASW:

Predictive Analysis Software

QC:

quality control

SPE:

solid phase extraction

UPLC-MS/MS:

ultra-performance liquid chromatography with tandem mass spectrometry

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Acknowledgements and Disclosures

The authors thank Kazue Ogata of Department of Clinical Pharmacy, Oita University Hospital, for technical assistance. We have no conflict of interest to disclose.

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Authors and Affiliations

  1. Department of Clinical Pharmacy, Oita University Hospital, 1-1 Hasama-machi, Oita, 879-5593, Japan

    Yosuke Suzuki, Hiroyuki Ono, Ryota Tanaka, Yuhki Sato & Hiroki Itoh

  2. Department of Medication Use Analysis and Clinical Research, Meiji Pharmaceutical University, 2-522-1 Noshio, Kiyose, Tokyo, 204-8588, Japan

    Yosuke Suzuki & Keiko Ohno

  3. Department of Urology, Faculty of Medicine, Oita University, 1-1 Hasama-machi, Oita, 879-5593, Japan

    Fuminori Sato & Hiromitsu Mimata

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  1. Yosuke Suzuki
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Correspondence to Yosuke Suzuki.

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Suzuki, Y., Ono, H., Tanaka, R. et al. Recovery of OATP1B Activity after Living Kidney Transplantation in Patients with End-Stage Renal Disease. Pharm Res 36, 59 (2019). https://doi.org/10.1007/s11095-019-2593-8

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