Pharmacodynamic and pharmacokinetic interactions of almitrine bismesylate.

Repeated administration of almitrine bismesylate, 50 mg b.i.d., to six healthy volunteers for 14 days did not alter any of the kinetic parameters of antipyrine, a test compound which measures the hydroxylating capacity of hepatic drug metabolising enzymes. Similarly, almitrine has no effect on the absorption, distribution or elimination of either erythromycin or digoxin, thus, it is unlikely that drug-kinetic interactions are likely to be important in clinical practice. Arterial oxygen tension (PaO2) is significantly increased (p less than 0.05) in 34 chronic bronchitic patients administrated almitrine bismesylate, 50 mg b.i.d. for 3 months. This improvement in hypoxia (9%) is negatively related to the initial PaO2 (p less than 0.01) and positively related to almitrine plasma concentrations (p less than 0.05). Thus, for each 100 ng X ml-1 increase in drug levels, there is an approximate 2 mmHg increase in PaO2, but there is a suggestion that levels greater than 800 ng X ml-1 may reduce or inhibit activity. The results suggest that the hypoxic state of the individual may modulate the activity of almitrine and influence the drug levels, but further work is required to substantiate these preliminary findings.