Doxapram

The principal pharmacological action of doxapram is an increase in minute volume produced primarily by an increase in tidal volume and to a lesser extent by changes in respiratory rate.

Pharmacodynamic effects

Neuropharmacological studies have shown that the primary sites of action of doxapram are the peripheral carotid chemoreceptors. It is considered that this site of action of doxapram is responsible for its relative specificity of action; it is only following large doses of doxapram that non-specific central nervous system stimulation occurs.

Following an I.V. bolus injection of 1.5mg/kg doxapram, the plasma concentration of doxapram declined in a multi-exponential manner. The mean half-life from 4–12 hours was 3.4 hours (range 2.4–4.1 hours). The mean apparent volume of distribution was 1.5 litres/kg and the whole body clearance was 370ml/min. Renal clearance was not related to urine flow or pH, but increased progressively with time over the first 12 hours. The mean 0–24 hour renal clearance values for individual volunteers ranged from 1.1 to 14.1ml/min. The rate of decline of plasma concentration appeared to decrease after 12 hours. Doxapram was extensively metabolised, and less than 5% of an I.V. dose was excreted unchanged in the urine in 24 hours.

Reproduction studies have been performed in rats at doses up to 1.6 times the human dose and have revealed no evidence of impaired fertility or harm to the foetus associated with the use of doxapram. Acute toxicity studies in several animal species suggest impairment of the central nervous system at high doses.