The effects in volunteers of BW12C, a compound designed to left-shift the blood-oxygen saturation curve

BW12C, a potent left-shifting anti-sickling compound in vitro, was administered to normal healthy male Caucasian volunteers. Doses of 2-20 mg kg-1 given by intravenous infusion over 1 h caused a dose-dependent left-shift of the blood-oxygen saturation curve and at the highest dose some 16% of the haemoglobin existed in a high affinity form. Peak left-shift was observed at the end of infusion and decayed thereafter with a mean half-life of approximately 3 h. There were no adverse systemic effects, either clinical, biochemical or haematological, but there was some local irritation at the intravenous infusion site if the infusion was too concentrated. Pharmacokinetic measurements indicated uptake into erythrocytes, low levels in plasma and a volume of distribution not appreciably greater than the blood volume. A pilot radiolabel study indicated extensive metabolism with elimination into the urine.