Accumulation of debrisoquine by platelets in vivo: a model of events at the peripheral adrenergic neurone.

The possibility that uptake of D by human platelets might reflect its accumulation in the post-ganglionic adrenergic neurone, and hence be a useful predictor of hypotensive response, was investigated. During chronic oral dosage of D in three hypertensive patients average concentrations of the drug in blood fractions relative to plasma were: platelet rich plasma, 2.93; whole blood, 2.23; red cells plus granulocytes, 0.75. These findings indicate extensive uptake of D by platelets but not by other cells. After single oral doses of 30 mg debrisoquine to four healthy volunteers platelets continued to accumulate the drug over at least 24 h. Although platelet D concentrations varied between subjects their platelet/plasma drug concentration ratios were similar. Amitriptyline (75 mg p.o.) given 2 h before a single 30 mg oral dose of D inhibited platelet uptake of the latter by 40 ± 14 s.d.% over a 24 h period. Platelets accumulated D but not its inactive 4-hydroxy metabolite. During chronic dosage of D in 10 patients the mean pre-dose platelet/plasma D concentration ratio was 8.52 ± 429 s.d. Within a 12 h dosing interval the concentration of D was constant in platelets but varied two-fold in plasma. Uptake of D by platelets approached saturation with increasing plasma D concentrations. After chronic D therapy in patients the fall in standing diastolic bp was more closely correlated with plasma D concentration ( = -0.88; < 0.001) than with platelet D concentration ( = -0.65; < 0.05). In relation to the therapeutic response to D, observations 3-5 but not 7 are consistent with a view of the platelet as a useful model of the peripheral adrenergic neurone.