1 The possibility that in vivo 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.
2 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.
3 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.
4 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.
5 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.
6 Uptake of D by platelets approached saturation with increasing plasma D concentrations.
7 After chronic D therapy in patients the fall in standing diastolic bp was more closely correlated with plasma D concentration (r = -0.88; P < 0.001) than with platelet D concentration (r = -0.65; P < 0.05).
8 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.