Objectives: Study of the acute and chronic effects of low-dose almitrine therapy in stable hypoxaemic patients with chronic bronchitis and emphysema.
Methods: A low daily dose of 75 mg almitrine bismesylate was administered for six months in 23 patients with chronic bronchitis and emphysema. Nine patients (group 1) were placed on oral almitrine bismesylate 25 mg t.i.d. after they had received a single intravenous dose of 60 mg almitrine three months earlier. Fourteen additional patients, seven receiving almitrine (group 2) and seven placebo (group 3) were randomized for a 6 month double-blind evaluation of both acute and chronic effects of 75 mg almitrine on pulmonary gas exchange and on pulmonary haemodynamics. All patients were followed-up with regular measurements of blood gases, body plethysmography and with evaluation of peripheral nerve function.
Results: Acute effects of almitrine were a significant increase in arterial oxygen tension by 14 mmHg after intravenous (p < 0.001) and by 15 mmHg after oral administration (p < 0.001), amelioration of hypercapnia, a slight transient increase in mean pulmonary artery pressure from 26 +/- 7 to 29 +/- 6 mmHg (NS) and a decrease of shunt due to improvement in ventilation/perfusion mismatching. In contrast, no acute changes in blood gases and pulmonary pressures were seen in the placebo group. A combination of almitrine with oxygen (8-10 L/min) was most effective in amelioration of hypoxaemia and shunt. With chronic almitrine therapy, the improvements in gas exchange persisted without elevation of pulmonary artery pressure (26 +/- 8 mmHg), whereas a negative trend in change of blood gases and pulmonary artery pressure occurred in the placebo treated group (NS). No significant changes in external ventilation, other spirometric parameters or adverse effects concerning peripheral nerve function were seen after almitrine or placebo treatment. The elimination of almitrine was fitted to a three compartment model and the terminal half-life in the patient population was found to be 32 +/- 29 days after intravenous dosing.
Conclusion: Acute and six-month almitrine bismesylate therapy at a low daily dose of 75 mg is found to be safe, even in severely compromised patients, with regard to pulmonary haemodynamics and peripheral nerve function. The agent is beneficial to pulmonary gas exchange, with reduction of hypercapnia, of intrapulmonary shunt and also with regard to sustained elevation of arterial oxygen tension. A combination with inhaled oxygen seems especially efficacious.