Simvastatin and lovastatin, but not pravastatin, interact with MDR1

T. Sakaeda, K. Takara, M. Kakumoto, N. Ohmoto, T. Nakamura, K. Iwaki, Yusuke Tanigawara, K. Okumura

Research output: Contribution to journalArticle

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Abstract

The 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, pravastatin, was compared with simvastatin and lovastatin from the viewpoint of susceptibility to interaction with or via the multidrug transporter, MDR1 (P-glycoprotein). This was carried out using the MDR1-overexpressing cell line LLC-GA5-COL150, established by transfection of MDR1 cDNA into porcine kidney epithelial LLC-PK1 cells, and [3H]digoxin, which is a well-documented substrate for MDR1. Pravastatin, at 25-100 μM, had no effect on the transcellular transport of [3H]digoxin whereas simvastatin and lovastatin suppressed the basal-to-apical transport of [3H]digoxin and increased the apical-to-basal transport. It was suggested that recognition by MDR1 was due to the hydrophobicity. In conclusion, simvastatin and lovastatin are susceptible to interaction with or via MDR1, but pravastatin is not. This is important information when selecting the HMG-CoA reductase inhibitors for patients taking drugs that are MDR1 substrates.

Original languageEnglish
Pages (from-to)419-423
Number of pages5
JournalJournal of Pharmacy and Pharmacology
Volume54
Issue number3
DOIs
Publication statusPublished - 2002

Fingerprint

Pravastatin
Lovastatin
Simvastatin
Digoxin
Oxidoreductases
LLC-PK1 Cells
Transcytosis
P-Glycoprotein
Hydrophobic and Hydrophilic Interactions
Transfection
Swine
Complementary DNA
Epithelial Cells
Kidney
Cell Line
Pharmaceutical Preparations
3-hydroxy-3-methylglutaryl-coenzyme A

ASJC Scopus subject areas

  • Pharmacology
  • Pharmaceutical Science

Cite this

Sakaeda, T., Takara, K., Kakumoto, M., Ohmoto, N., Nakamura, T., Iwaki, K., ... Okumura, K. (2002). Simvastatin and lovastatin, but not pravastatin, interact with MDR1. Journal of Pharmacy and Pharmacology, 54(3), 419-423. https://doi.org/10.1211/0022357021778493

Simvastatin and lovastatin, but not pravastatin, interact with MDR1. / Sakaeda, T.; Takara, K.; Kakumoto, M.; Ohmoto, N.; Nakamura, T.; Iwaki, K.; Tanigawara, Yusuke; Okumura, K.

In: Journal of Pharmacy and Pharmacology, Vol. 54, No. 3, 2002, p. 419-423.

Research output: Contribution to journalArticle

Sakaeda, T, Takara, K, Kakumoto, M, Ohmoto, N, Nakamura, T, Iwaki, K, Tanigawara, Y & Okumura, K 2002, 'Simvastatin and lovastatin, but not pravastatin, interact with MDR1', Journal of Pharmacy and Pharmacology, vol. 54, no. 3, pp. 419-423. https://doi.org/10.1211/0022357021778493
Sakaeda, T. ; Takara, K. ; Kakumoto, M. ; Ohmoto, N. ; Nakamura, T. ; Iwaki, K. ; Tanigawara, Yusuke ; Okumura, K. / Simvastatin and lovastatin, but not pravastatin, interact with MDR1. In: Journal of Pharmacy and Pharmacology. 2002 ; Vol. 54, No. 3. pp. 419-423.
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