Trial of a new water soluble intravenous anaesthetic

Volunteer subjects will be given an intravenous injection of the test anaesthetic, PHAX001 or propofol in a subject and observer blinded randomised manner. Each subject will receive only one dose of one of the anaesthetic drugs. Doses will be increased or decreased from one subject to the next according to response. Twenty four subjects will be allocated randomly to receive either propofol or PHAX001; n = 12 per group. Two anaesthetists will be involved, one to care for the patient and the other, the drug administering anaesthetist. The drug administering anaesthetist will break the code for each subject in turn from a computer program after all preparations are made for drug injection i.e., after an individual subject and the caring anaesthetist have been screened by a curtain between them and the drug administering anaesthetist; the code will allocate the drug treatment randomly to that subject - propofol or PHAX001. For the first subject randomised to receive the drug they will be given propofol 2 mg/kg or PHAX001 0.55 mg/kg. The observations and measurements listed below will be made. That subject will not receive any more propofol or PHAX001. The dosing for the next subject to receive a particular drug will be determined by the response of the first subject given that drug. If the first subject did not achieve a bispectral index reading on the EEG monitor (BIS) of 50 or less, then for propofol the dose would be 3 mg/kg in the second subject randomised to receive propofol or PHAX001 0.75 mg/kg in the case of the second subject randomised to receive PHAX001. If the first subject did achieve a BIS of 50 or less, then for propofol the dose would be 1 mg/kg and for PHAX001 0.25 mg/kg. Thereafter the dosing will be: 1) a decrease of dose of 25% if all subjects so far treated with that drug achieved a BIS below 49 or, 2) an increase of dose of 25% if none of the subjects so far treated with that drug had achieved a BIS of 50 or less, or, 3) in the case that there have been some subjects treated with this drug that have achieved BIS values of 50 or less than 50 and others with BIS values of greater than 50 then either: a) if the last subject's response was a BIS of 50 or less, then the dose of drug for the next subject to receive this drug will be mid way between that subject's dose and the dose given to the most recent previous subject given that drug and who achieved a BIS of 50 or above. b) In the case of the last response being a BIS of 50 or greater, then the dose of drug for the next subject to receive this drug will be mid way between the dose for that subject and the dose given to the most recent previous subject given that drug who achieved a BIS of 49 or below. 4) The latter will be repeated for each drug series until the dose range variations have become small and five or six subjects have achieved a BIS value of 50 or less having received the same dose +/- 10% of drug. These 6 doses achieving anaesthetic levels of BIS (50 or less) will be combined to calculate the mean +/- sem induction dose. Time for induction of anaesthesia and recovery will be measured using clinical observations and BIS monitoring. Effects on blood pressure, heart rate and respiration will also be measured.