2 S-ketamine oral thin film pharmacokinetics Table 2.2: Peak concentration (CMAX), time of CMAX (TMAX), and areaunder-the time-concentration curve (AUC) of S-ketamine, S-norketamine and Shydroxynorketamine following 50 and 100 mg S-ketamine oral thin film (OTF). 50mg S-ketamine OTF 100mg S-ketamine OTF S-ketamine CMAX (ng/ml) 96 (81 – 111) 144 (127 – 161) CMAX (nM) 420 (360 – 480) 600 (500 – 700) TMAX (min) 18.8 (16.6 – 21.2) 19.1 (17.1 – 21.2) AUC (0-6 h) (ng/ml.min) 8,363 (7,263 – 9,464) 13,347 (11,933 – 14,760) S-norketamine CMAX (ng/ml) 276 (243-308) 426 (362-489) CMAX (nM) 1,130 (970 – 1300) 1,475 (1,122 – 2,237) TMAX (min) 61 (53-68) 78 (66-91) AUC (0-6 h) (ng/ml.min) 38,497 (34,131 – 42,863) 67,959 (60,045 – 75,872) S-hydroxynorketamine CMAX (ng/ml) 101 (89 – 115) 189 (160 – 218) CMAX (nM) 340 (293 – 387) 619 (594 – 644) TMAX (min) 81 (69-92) 109 (89 – 130) AUC (0-6 h) (ng/ml.min) 24,087 (20,694 – 27,480) 44,972 (38,563 – 51,382) Values are mean (±95% confidence interval). Adverse Events Eighteen subjects reported at least one adverse event. In total, there were 97 adverse events. None were serious adverse events. See for the prevalence of events Table 2.3 on page 24. We relate one adverse event (numbness of the tongue) directly to the application of the oral thin film, the remaining events were drug-associated. All subjects experienced dissociative side effects (drug high, changes in internal and external perception) as derived from the Bowdle questionnaire. The accompanying paper on the OTF pharmacodynamic effects presents these data in detail.4 During the first hour after application of the OTF, blood pressure increased with mean arterial pressure 92 ±11 mmHg (mean ± SD), 97 ±7 mmHg and 104 ±6 mmHg at baseline (prior to application) and 10 and 60 min after the application of the 50 mg S-ketamine OTF, respectively, and 95 ±15 mmHg, 97 ±11 mmHg and 108 ±10 mmHg at baseline and 10 and 60 min after the application of the 100 mg S-ketamine OTF. 23
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