THE EFFECT OF HYPOXEMIA ON DRUG DISPOSITION IN CHRONIC RESPIRATORY-FAILURE

Objective: The influence of hypoxaemia on the disposition of two commo n drugs has been examined in ten adults with stable chronic respirator y failure. Methods: There were two experimental periods in this cross- over study: during these periods supplemental oxygen was either withhe ld or administered to impose clinical hypoxaemia or maintain normoxaem ia, respectively. Each participant received either oral (40 mg) or int ravenous (20 mg) frusemide combined with oral paracetamol (500 mg) on consecutive days of the two experimental periods. Results: The total ( bound plus unbound) plasma clearance of frusemide during hypoxaemia (a rterial oxygen tension, PaO2 less than or equal to 50 Torr) was not si gnificantly different from the value during normoxaemia (PaO2 greater than or equal to 60 Torr) [76.9 and 62.4 ml . min(-1)]. The volume of distribution was not affected by acute hypoxaemia (121 ml . kg(-1) wit hout and 109 ml . kg(-1) with oxygen; P > 0.05). Renal and non-renal c learances of frusemide were similar during the period of hypoxaemia (3 1 and 38 ml . min(-1), respectively) compared to respective values dur ing supplemental oxygen delivery (29 and 32 ml . min(-1)). The absolut e bioavailability of frusemide during hypoxaemia (0.62) was not differ ent to that obtained during normoxaemia (0.56). The combined sodium an d potassium excretion rate (expressed as a function of the frusemide e xcretion rate) was not altered by changing the oxygen tension. The pha rmacokinetics of paracetamol were unaffected by hyperaemia.