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Pharmaceutics 2017, 9(4), 42; https://doi.org/10.3390/pharmaceutics9040042

Study of Statin- and Loratadine-Induced Muscle Pain Mechanisms Using Human Skeletal Muscle Cells

1
Faculty of Pharmacy, Université de Montréal, Montreal, QC H2X 0A9, Canada
2
Centre de Recherche du Centre Hospitalier de l’Université de Montréal (CRCHUM), Montreal, QC H2X 0A9, Canada
*
Author to whom correspondence should be addressed.
Received: 31 August 2017 / Revised: 30 September 2017 / Accepted: 1 October 2017 / Published: 10 October 2017
(This article belongs to the Special Issue Pharmacokinetics and Drug Metabolism in Canada: The Current Landscape)
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Abstract

Many drugs can cause unexpected muscle disorders, often necessitating the cessation of an effective medication. Inhibition of monocarboxylate transporters (MCTs) may potentially lead to perturbation of l-lactic acid homeostasis and muscular toxicity. Previous studies have shown that statins and loratadine have the potential to inhibit l-lactic acid efflux by MCTs (MCT1 and 4). The main objective of this study was to confirm the inhibitory potentials of atorvastatin, simvastatin (acid and lactone forms), rosuvastatin, and loratadine on l-lactic acid transport using primary human skeletal muscle cells (SkMC). Loratadine (IC50 31 and 15 µM) and atorvastatin (IC50 ~130 and 210 µM) demonstrated the greatest potency for inhibition of l-lactic acid efflux at pH 7.0 and 7.4, respectively (~2.5-fold l-lactic acid intracellular accumulation). Simvastatin acid exhibited weak inhibitory potency on l-lactic acid efflux with an intracellular lactic acid increase of 25–35%. No l-lactic acid efflux inhibition was observed for simvastatin lactone or rosuvastatin. Pretreatment studies showed no change in inhibitory potential and did not affect lactic acid transport for all tested drugs. In conclusion, we have demonstrated that loratadine and atorvastatin can inhibit the efflux transport of l-lactic acid in SkMC. Inhibition of l-lactic acid efflux may cause an accumulation of intracellular l-lactic acid leading to the reported drug-induced myotoxicity. View Full-Text
Keywords: statins; loratadine; drug-transporters; MCT; monocarboxylate transporters; lactic acid; skeletal muscle cell; drug-induced muscle disorders statins; loratadine; drug-transporters; MCT; monocarboxylate transporters; lactic acid; skeletal muscle cell; drug-induced muscle disorders
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Leung, Y.H.; Turgeon, J.; Michaud, V. Study of Statin- and Loratadine-Induced Muscle Pain Mechanisms Using Human Skeletal Muscle Cells. Pharmaceutics 2017, 9, 42.

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