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Pharmacokinetic Significance of Renal OAT3 (SLC22A8) for Anionic Drug Elimination in Patients with Mesangial Proliferative Glomerulonephritis

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Purpose

Our previous studies showed that the mRNA level of human organic anion transporter (hOAT) 3 in the kidney was correlated with the rate of elimination of an anionic antibiotic cefazolin. However, the correlation coefficient was not so high. In the present study, therefore, we enrolled more patients to examine whether additional factors were responsible for the correlation.

Methods

hOAT mRNA levels in renal biopsy specimens were quantified using the real-time polymerase chain reaction method. The elimination rates for the free fraction of cefazolin were determined in patients with various renal diseases.

Results

In the present study, the coefficient of correlation between the hOAT3 mRNA level and the elimination rates for the free fraction of cefazolin was not so high in the patients overall as in our previous study (r = 0.536). However, following the classification of renal diseases, a better correlation was obtained in patients with mesangial proliferative glomerulonephritis (r = 0.723). In contrast, multiple regression analyses including gender, age, and liver function did not result in any improvements in the correlation coefficients.

Conclusions

These results suggest that the hOAT3 mRNA level is a significant marker of pharmacokinetics with which to predict the rate of elimination of cefazolin in patients with mesangial proliferative glomerulonephritis.

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Acknowledgments

This work was supported by a grant-in-aid for Comprehensive Research on Aging and Health from the Ministry ofHealth and Welfare of Japan (H15-Choju-006), by a grant-in-aid for Scientific Research from the Ministry of Education,Culture, Sports, Science, and Technology of Japan, by agrant-in-aid from the Japan Research Foundation for Clinical Pharmacology, and by the 21st Century COE program“KnowledgeInformation Infrastructure for Genome Science.”

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Authors and Affiliations

  1. Department of Pharmacy, Kyoto University Hospital, Faculty of Medicine, Kyoto University, Sakyo-ku, Kyoto, Japan

    Yuji Sakurai, Hideyuki Motohashi, Ken Ogasawara, Tomohiro Terada, Satohiro Masuda, Toshiya Katsura & Ken-ichi Inui

  2. Department of Nephrology, Shizuoka Prefectural Hospital, Shizuoka, Japan

    Noriko Mori

  3. Department of Clinical Biology and Medicine, Course of Biological Medicine, School of Medicine, University of Tokushima, Tokushima, Japan

    Motokazu Matsuura & Toshio Doi

  4. Division of Artificial Kidneys, Kyoto University Hospital, Faculty of Medicine, Kyoto University, Kyoto, Japan

    Atsushi Fukatsu

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  1. Yuji Sakurai
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Correspondence to Ken-ichi Inui.

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Sakurai, Y., Motohashi, H., Ogasawara, K. et al. Pharmacokinetic Significance of Renal OAT3 (SLC22A8) for Anionic Drug Elimination in Patients with Mesangial Proliferative Glomerulonephritis. Pharm Res 22, 2016–2022 (2005). https://doi.org/10.1007/s11095-005-8383-5

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