However, in practice, doseresponse patterns are significantly complicated due to many other interactions with (i) multiple targets (receptors) of different affinities to the active compound, (ii) other regulatory proteins or mediators in the networks involved in the adaptive stress response, (iii) feedback down regulations in the molecular signaling pathways, and/or (iv) metabolic transformation of active ligands into metabolites, a secondary ligand, which have different affinities to various receptors of the adaptive stress response [69]
The differing toxicities of ionizable organic compounds at different pH values can be attributed to the distinct permeabilities of the existing species (i.e., neutral and ionized forms) because neutral species can permeate biomembranes and become trapped in cells faster than the corresponding charged species, resulting in distinct differences in the internal concentrations
The schedule skips missed doses instead of doubling the next injection
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The escalation schedules are similar through the first three tiers but diverge at the higher doses
Inflammopharmacology 14:214221 Sikiric P, Seiwerth S, Brcic L et al (2010) Revised Roberts cytoprotection and adaptive cytoprotection and stable gastric pentadecapeptide BPC 157
