KINETICS OF METHEMOGLOBIN AND SERUM NITROGEN-OXIDE PRODUCTION DURING INHALATION OF NITRIC-OXIDE IN VOLUNTEERS

Inhaled nitric oxide is used increasingly to treat pulmonary hypertens ion and ventilation/perfusion mismatching in seriously ill patients, b ut little is known of the pharmacokinetics of its two principal metabo lites, methaemoglobin and nitrogen oxides (nitrates and nitrites). We have studied the changes in these metabolites in six healthy volunteer s 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(-1) at stan dard temperature and pressure, corresponding to 74% of the inhaled dos e. During inhalation, methaemoglobin increased monoexponentially with a time constant of 45.6 (11.1) min by 1.77 (0.47)% of total haemoglobi n. Serum nitrogen oxides increased from 36.7 (7.6) to 124 (17) mu mol litre(-1), with a time constant of 172 (91.4) min and a volume of dist ribution of 331 (104) ml kg(-1). The volume of distribution for methae moglobin calculated from nitric oxide uptake and the increase in metha emoglobin, was, on average, 14.3% less than predicted blood volume, su ggesting that most of the absorbed nitric oxide initially forms methae moglobin. Serum nitro gen oxides declined initially after inhalation c eased but then increased to a second peak between 45 and 180 min later . The cause of the second peak was not determined.