PHARMACOKINETICS AND PHARMACODYNAMICS OF TUCARESOL, AN ANTISICKLING AGENT, IN HEALTHY-VOLUNTEERS

1 Tucaresol is an orally administered antisickling agent which increases the oxygen affinity of haemoglobin. 2 The pharmacokinetics, effects on moderate graded exercise and psychometric performance of tucaresol were examined in a double-blind, placebo-controlled, parallel groups study in 12 healthy men. 3 Three doses of tucaresol were given at 48 h intervals intended to modify 15, 25 and 32.5% of a subject's haemoglobin to a high affinity form (%MOD). 4 Mean peak %MOD was 34%. Mean C-max values in plasma and erythrocytes were 81.4 and 1459 mu g ml(-1), respectively. 5 Heart rate, compared with baseline, increased in the tucaresol group with the greatest changes at the highest %MOD and workload. There were no differences between groups in psychometric test performance. 6 Three volunteers on active drug developed fever, rash and tender cervical lymphadenopathy with onset 7-10 days from the start of dosing, suggesting an immune mechanism. 7 The acute increase in oxygen affinity with tucaresol is physiologically well-tolerated, but the utility of tucaresol in the management of sickle cell disease will depend on the identification of a dosing regimen with a lower incidence of drug allergy.