Pharmacokinetics of digoxin were investigated in six healthy volunteers following one week of digoxin monotherapy 0.25 mg b.i.d., and during coadministration of metoclopramide 10 mg t.i.d. or cisapride 10 mg t.i.d.. Metoclopramide reduced the peak plasma concentration of digoxin from 1.5 +/- 0.2 ng/ml to 1.1 +/- 0.1 ng/ml (mean +/- SEM) (p = 0.05), cisapride lowered the peak concentration to 1.3 +/- 0.1 ng/ml (p = 0.14). Metoclopramide prolonged the time required to reach the peak concentration of digoxin from 2 hr to 2.7 hr (p = 0.17), cisapride did not. Digoxin AUC0-12 (743 +/- 79 ng/ml.min) was reduced by 12% on coadministration of cisapride (653 +/- 38 ng/ml.min, p = 0.22) and by 19% on coadministration of metoclopramide (605 +/- 34 ng/ml.min, p = 0.06). It is concluded that the gastrointestinal absorption of digoxin is reduced by both substances. Monitoring of the patient's clinical status should be recommended when metoclopramide and cisapride are coadministered.

1 In a placebo controlled double-blind study including 10 patients with heart failure the nisoldipine/digoxin interaction was studied. 2 Nisoldipine was shown to elevate digoxin plasma concentrations significantly by about 15% (trough levels). 3 During chronic combination therapy with nisoldipine trough levels and plasma concentrations 4 h after the morning dose of digoxin were 1.35 ± 0.14 and 1.92 ± 0.16 ng ml-' respectively, whereas they averaged to 1.16 ± 0.14 and 1.52 + 0.16 ng ml-1 with digoxin and placebo (P < 0.05; mean + s.e. mean). 4 Systolic time intervals were significantly altered by nisoldipine co-administration compared with digoxin plus placebo. 5 In certain patients the elevation of digoxin plasma levels due to nisoldipine coadministration could be of clinical relevance.

The effect of two different doses of nitrendipine on plasma digoxin levels, urinary recovery and systolic time intervals was investigated in 8 healthy volunteers. Following a loading dose, digoxin 0.25 mg b.d.p.o. was given alone for 2 weeks. Then 0.25 mg digoxin b.d. was administered for two 1-week periods combined with nitrendipine 10 mg or 20 mg once daily. The study was completed with another digoxin monotherapy phase lasting 7 days. Nitrendipine 20 mg daily led to a significant increase in plasma digoxin levels and in its area under the plasma concentration-time curve AUC (0-12) was 9.7 ng ml-1h when digoxin alone was given and 11.2 ng ml-1h on co-administration of the calcium antagonist. Urinary recovery and renal clearance of digoxin were slightly but not significantly increased by nitrendipine. Nitrendipine 10 mg once daily caused a small, insignificant tendency to elevate the plasma digoxin level. Nitrendipine co-administration (10 and 20 mg once daily) did not significantly alter systolic time intervals, as non-invasively measured haemodynamic parameters, compared to digoxin treatment alone. Thus, nitrendipine 20 mg daily caused a significant increase in plasma digoxin concentrations and in its AUC, which would rarely be of clinical relevance.

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