Overall pharmacokinetics of CP are apparently not affected during eightfold dose escalation. However, there is a shift in the relative contribution of different clearances to systemic CP clearance in favor of inactivating elimination pathways, thereby indicating saturation of bioactivating enzymes during dose escalation. Besides individual enzyme capacity, hydration and concomitant medication with dexamethasone modulated CP disposition.
Elderly patients are more sensitive to the sedative action of midazolam than young patients, and the sensitivity is caused by age-dependent pharmacodynamic alterations. The age-adjusted doses used are both effective (for sedative amnesia) and safe (in terms of arterial oxygen saturation, heart rate, and blood pressure.
Following dose escalation of CP, dividing the high dose over 2 days instead of one single infusion may favorably impact the metabolism of CP in terms of bioactivation. In addition, on day 2 of a split regimen, renal elimination of CP is decreased, which implies that more drug is available for metabolism.
Chemical shifts and long‐range 13C, 1H coupling constants to the two carbonyl C atoms were determined for a series of ethyl 2‐acyloxy‐2‐alkenoates. The 3J(C,H) coupling constant across the double bond is 9.5–10.1 Hz for the E‐ and 2.9–3.8 Hz for the Z‐isomer. 3J(C,H) values, therefore, may be used as a criterion for E/Z differentiation even if only one isomer is available. 13C chemical shift data, in contrast, cannot be employed for a straightforward differentiation.
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