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      "text": "Pitolisant pilot study, first published in 2007, indicates massive plasma level variability",
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      "text": "The omission of pharmacokinetic tables is a striking red flag – and the paper used a crude trick by saying “greater than” versus stating how high the levels spiked, much less showing a distribution.",
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      "text": "plasma levels: 100.6 ng/ml",
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      "text": "Tiprolisant dosages were performed at the end of the treatment period with a median sampling time at 3.75 h after the last drug intake. The plasma level average was 100.6±78.1 ng/ml (n=17). Elevated plasma levels (> 150 ng/ml) were observed in 5 patients, in some cases related to the experience of adverse events occurring a few hours after drug intake.",
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      "text": "The first patient data was published in 2007, when the drug was still known as tiprolisant. Bioprojet conducted a phase 2 sequential two-week single arm study for EDS in narcoleptic patients – 22 adults, with a week of placebo then 40 mg/day for the second week. The first danger signal is that plasma levels were highly elevated and variable – a stark contrast to claims in later trials which conceal the risk given the drug’s CYP2D6 liability. Plasma levels after a week averaged 101 ng/ml – a level significantly higher than that listed in the FDA clinical review, based on trials that tried to downplay the hERG and QT prolongation risk. Moreover, the standard deviation was 78 ng/ml, indicating massive variability across patients. Five of the patients had plasma levels greater “>150 ng/ml.” The omission of pharmacokinetic tables is a striking red flag – and the paper used a crude trick by saying “greater than” versus stating how high the levels spiked, much less showing a distribution.",
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      "text": "An inverse agonist of the histamine H3 receptor improves wakefulness in narcolepsy: Studies in orexin-/- mice and patients",
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      "text": "The plasma level average was 100.6±78.1 ng/ml (n=17). Elevated plasma levels (> 150 ng/ml) were observed in 5 patients, in some cases related to the experience of adverse events occurring a few hours after drug intake. — An inverse agonist of the histamine H3 receptor improves wakefulness in narcolepsy: Studies in orexin-/- mice and patients",
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