2 S-ketamine oral thin film pharmacokinetics Simulations In-silico simulations were performed to determine the effect of changes in the duration that the 50 mg S-ketamine oral thin film stayed sublingually (before the subjects was allowed to swallow) on plasma concentrations of S-ketamine and its metabolites. To that end, factor D1 was either increased or decreased by a factor (F) of 2, F1 was adjusted assuming it converges to 1 exponentially with D1 (i.e. F1 approaches 1 in case the OTF remains sublingually and is not swallowed), F2 was adjusted so that total bioavailability remains constant, and changes in D2 followed changes in D1 assuming D2 is the sum of D1 and gastrointestinal lag times. D1 is the duration of absorption, D2 is the duration of absorption from the gastrointestinal tract. F1 and F2 are the S-ketamine bioavailability from the oral mucosa and gastrointestinal tract, respectively. 19
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