Drug therapy had been used in these patients prior to the study. This included oral theophylline (eight patients), salbutamol (two patients), amoxacillin (two patients), almitrine (two patients), cysteine derivatives (five patients) and furosemide, K+ supplements, oxitropium and occasionally nitrates (one patient). Only four patients received theophylline between the two experiments. In all cases, theophylline was interrupted 24 hours prior the experiment. Prior and during the study, the patients drank the same amount of coffee (one to two cups per day) and none of them ate chocolate. Eight of the subjects were occasional wine drinkers (one to three cups per day). website
All subjects had normal hepatic function tests. Renal function was appropriate for their age group as creatinine clearance was 97 ± 7 ml/min, prior to oxygen therapy.
Once full clinical and laboratory examination was completed, the candidates were asked to empty their bladders prior to receiving 4 mg/kg of theophylline infused intravenously over a period of 20 minutes with a syringe pump. Blood samples were drawn prior to and 0.5, 1, 1.5, 2, 4, and 6 hours after the administration of theophylline. Urine was collected for the six-hour period. Following this first phase, the patients received oxygen through a nasal cannula at a rate of 1.5 to 2 L/min to obtain a Pa02 of at least 65 mm Hg. After 48 hours, and still on oxygen, theophylline kinetics were reassessed following the same protocol as described above.
Theophylline in plasma was assayed by HPLC as described elsewhere. Theophylline and its three major metabolites in urine, 1,3-dimethyluric acid (1,3-DMU), 3-methylxantine (3-MX) and 1-methyluric acid (1-MU), were assayed by HPLC as described by St. Pierre et al.
Theophylline plasma concentrations-time curve was best described by a two compartment model, with first order distribution and elimination.