Kinetics of methaemoglobin and serum nitrogen oxide production during inhalation of nitric oxide in volunteers

Inhaled nitric oxide is used increasingly to treat pulmonary hypertension and ventilation/perfusion mismatching in seriously ill patients, but little is known of the pharmacokinetics of its two principal metabolites, methaemoglobin and nitrogen oxides (nitrates and nitrites). We have studied the changes in these metabolites in six healthy volunteers during and after 3 h inhalation of 100 volumes per million of nitric oxide. Mean nitric oxide uptake was 0.49 (SD 0.08) ml min-1at standard temperature and pressure, corresponding to 74% of the inhaled dose. During inhalation, methaemoglobin increased monoexponentially with a time constant of 45.6 (11.1) min by 1.77 (0.47)% of total haemoglobin. Serum nitrogen oxides increased from 36.7 (7.6) to 124 (17) μmol litre-1, with a time constant of 172 (91.4) min and a volume of distribution of 331 (104) ml kg-1. The volume of distribution for methaemoglobin calculated from nitric oxide uptake and the increase in methaemoglobin, was, on average, 14.3% less than predicted blood volume, suggesting that most of the absorbed nitric oxide initially forms methaemoglobin. Serum nitrogen oxides declined initially after inhalation ceased but then increased to a second peak between 45 and 180 min later. The cause of the second peak was not determined.