Pharmacokinetic interaction of acetylsalicylic acid and dipyridamole.

It is often recommended that acetylsalicylic acid (ASA) and dipyridamole should be given together in order to obtain secondary prophylaxis against certain ischaemic diseases. Therefore, the possible pharmacokinetic interactions between these agents were assessed following single-dose exposures in 14 healthy volunteers. The plasma concentrations of ASA, salicylic acid (SA) and dipyridamole were measured by selective h.p.l.c. techniques. It was found that, while dipyridamole kinetics were unaffected by concurrent ASA, concurrent dipyridamole significantly enhanced the peak concentration (24%) and AUC (27%) of ASA. Thus, co-administered dipyridamole might influence the anti-platelet effect of ASA.

Actions and interactions of acetylsalicylic acid, salicylic acid and diflunisal on platelet aggregation.

Acetylsalicylic acid (ASA) is increasingly employed in the secondary prophylaxis of thromboembolic diseases, due to its capacity to inhibit platelet aggregation. The anti-aggregatory effect of ASA on platelets can be inhibited in vitro by a high concentration of salicylic acid (SA). SA is generated in vivo upon ASA administration, and the SA thus formed might impair the antiplatelet effect of ASA. To assess this possibility, the platelet response to ASA was tested in healthy volunteers before and after medication for 1 week with ASA 1 g t.i.d., with SA 1 g t.i.d., and with the SA derivative diflunisal 0.5 g b.i.d. Pre-medication test doses of 1 g ASA always inhibited platelet aggregation in vivo. Neither treatment with SA nor diflunisal, producing plasma steady-state concentrations of about 1.0 and 0.35 mmol/l, respectively, inhibited platelet aggregation. Nor did administration of SA, diflunisal or ASA itself impair the anti-aggregatory effect of a fresh test dose of ASA. ASA inhibited platelet aggregation in vitro at 0.03 mmol/l, whereas SA and diflunisal failed to impair platelet aggregation until concentrations exceeding 2.0 and 0.5 mmol/l, respectively, were reached. These findings make it unlikely that SA formed upon administration of ASA would impair the anti-aggregating capacity of ASA.

Anticoagulant vs anti-platelet therapy as prophylactic against cerebral infarction in transient ischemic attacks.

156 patients with transient ischemic attacks (TIA) or reversible ischemic neurological deficit (RIND) were given prophylactic anticoagulant (AC) treatment against cerebral infarction in a prospective multicenter study from 5 hospitals in southern Sweden. After 2 months of AC treatment, 135 patients remained in the study and were randomized into 2 groups; one continued with AC treatment and one changed to anti-platelet therapy. The patients were followed for 12 months. No significant difference was seen between the 2 groups but 3 completed cerebral infarctions occurred during anti-platelet therapy against one during AC treatment. One cerebral hemorrhage was seen during AC treatment. All completed strokes occurred in men who initially had carotid symptoms. The number of patients with TIA/RIND was somewhat higher in the anti-platelet group whereas myocardial infarctions occurred more often during AC treatment. Compared to the natural history of untreated TIA/RIND both treatments were found to have a prophylactic effect against cerebral infarction.

Once-daily metoprolol in primary hypertension.

The antihypertensive effect of the selective beta-1-adrenoceptor blocker, metoprolol, administered once daily was evaluated in 32 patients with primary hypertension. After a 4-wk placebo period, the patients were treated with either 150 mg or 300 mg of metoprolol, once daily, for 8 wk. Initially and during the treatment periods blood was drawn for analysis of metoprolol in plasma, plasma renin activity (PRA), and electrolytes, and urine was collected for determination of the urinary aldosterone excretion. Metoprolol reduced the blood pressure measured up to 26 hr after the last dose. The percentage of responders to metoprolol (decrease of mean arterial pressure greater than or equal to 10% over placebo) was 40% for patients on 150 mg and 71% for patients on 300 mg. Except in the standing position, heart rates were reduced for 26 hr after a 150-mg dose. There was a correlation between pretreatment PRA levels and antihypertensive effect of metoprolol in patients on 300 mg metoprolol but not in patients on 150 mg. Urinary aldosterone decreased equally during treatment in responders and nonresponders. Antihypertensive effects and side effects did not correlate with plasma metoprolol concentrations.