Dose‐response relationship for disoprofol (ICI 35868; Diprivan)

The duration of sleep following intravenous administration of three doses of disoprofol (1.2 and 3 mg/kg) was compared with that following methohexione 1 or 2 mg/kg. Disoprofol and methohexitone were shown to be approximately equipotent. Side-effects were dose-related for both drugs, but the incidence was significantly less following disoprofol than methohexitone 2 mg/kg. The most frequent side-effects were pain on injection, myoclonia and hiccup. Studies of blood concentrations of disoprofol show that the profile is dose-independent and conforms to a two-compartment model with a very short distribution phase (about 2 minutes) and short elimination phase (about 70 minutes). Waking blood levels gave no indication of acute tolerance. Disoprofol would appear to be particularly useful for induction of a short period of sleep using a small dose given quickly, or for maintenance of sleep by continuous infusion.