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. 2016 Aug;174:140–160.e14. doi: 10.1016/j.trsl.2016.03.015

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© 2016 The Authors

This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

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Fig 3 — Time course interconversion of simvastatin lactone (SVL) and pravastatin lactone (PVL) in human plasma at different pH levels. The lactone forms of simvastatin and pravastatin were incubated with human plasma of modified pH (6.8–7.8) at a concentration of 50 μmol/L for 48 hours at 37°C. The percentages of lactone and hydroxy acid form recovered at different time points are expressed as mean ± standard deviation, (n = 6). Differences between samples of different pH were analyzed by 2-way analysis of variance followed by Bonferroni's post hoc test. Time course interconversion of SVL shows disappearance of SVL (A) and formation of simvastatin hydroxy acid form (B). a = pH 7.0 vs pH 7.6 (P < 0.05); pH 7.4 vs pH 6.8, 7.8 (P < 0.01); pH 6.8 vs pH 7.6, 7.8; pH 7.8 vs pH 7.0, 7.2 (P < 0.001). b = pH 6.8 vs pH 7.0, 7.2, 7.4, 7.6, 7.8; pH 7.0 vs pH 7.2, 7.4, 7.6, 7.8; pH 7.2 vs pH 7.4, 7.6, 7.8; pH 7.4 vs pH 7.6, 7.8; pH 7.6 vs pH 7.8 (P < 0.001). c = pH 6.8 vs pH 7.0, 7.2, 7.4, 7.6, 7.8; pH 7.0 vs pH 7.2, 7.4, 7.6, 7.8; pH 7.2 vs pH 7.4, 7.6, 7.8; pH 7.4 vs pH 7.6, 7.8 (P < 0.001); pH 7.6 vs pH 7.8 (P < 0.05). d = pH 6.8 vs pH 7.0, 7.2, 7.4, 7.6, 7.8; pH 7.0 vs pH 7.2, 7.4, 7.6, 7.8; pH 7.2 vs pH 7.4, 7.6, 7.8 (P < 0.001); pH 7.4 vs pH 7.6 (P < 0.05). e = pH 6.8 vs pH 7.0, 7.2, 7.4, 7.6, 7.8; pH 7.0 vs pH 7.2, 7.4, 7.6, 7.8; pH 7.2 vs pH 7.6, 7.8 (P < 0.001); pH 7.4 vs pH 7.2, 7.8 (P < 0.05). Time course interconversion of PVL shows disappearance of PVL (C) and formation of pravastatin hydroxy acid form (D). a = pH 7.6 vs pH 6.8, 7.4 (P < 0.01); pH 7.8 vs pH 6.8, 7.0, 7.2, 7.4; pH 7.2 vs pH 7.6 (P < 0.001). b = pH 6.8 vs pH 7.2, 7.4, 7.6, 7.8; pH 7.0 vs pH 7.2, 7.4, 7.6, 7.8; pH 7.2 vs pH 7.4, 7.6, 7.8; pH 7.4 vs pH 7.6, 7.8; pH 7.6 vs pH 7.8 (P < 0.001). c = pH 6.8 vs pH 7.0, 7.2, 7.4, 7.6, 7.8; pH 7.0 vs pH 7.2, 7.4, 7.6, 7.8; pH 7.2 vs pH 7.4, 7.6, 7.8; pH 7.4 vs pH 7.6, 7.8 (P < 0.001). d = pH 6.8 vs pH 7.0, 7.2, 7.4, 7.6, 7.8; pH 7.0 vs pH 7.4, 7.6, 7.8 (P < 0.001); pH 7.0 vs pH 7.2 (P < 0.01).