There was no relationship between the slight changes in theophylline clearance and the variations in Pa02. However, when the patients were divided into two groups according to their PaC02 values, with 45 mm Hg as the cutoff, it was apparent that subjects with normal PaC02 values (lower than 45 mm Hg), had significantly higher values of theophylline clearance than patients with PaC02 values above 45 (Fig 2). Moreover, when considering the ten patients before and after therapy, the changes in theophylline clearance were inversely correlated (r= —0.5264; p<0.02) with the values of PaC02 (Fig 3). so
The six-hour urinary recoveries of theophylline and its metabolites (3-MX, 1,3-DMU and 1-MU) are depicted in Table 3. As shown, oxygen therapy did not affect the pattern of urinary excretion of theophylline or its metabolites. On the other hand, the urinary recovery of theophylline metabolites was independent of previous treatment with theophylline but appeared weakly related to individual values of Pa02 (r = — 0.53, p<0.02 for 3-MX; r= -0.46, p<0.05 for 1,3-DMU; and r= -0.47, p<0.05 for 1-MU).
The results of this study showed that prior to oxygen therapy, theophylline clearance in our patients was not lower than that reported in healthy volunteers. The average value of theophylline clearance was not significantly decreased if the three exsmokers were excluded, eg, C1T = 0.90 ±0.11 ml/min/kg. On the other hand, after oxygen therapy, the changes in Pa02 in our patients with COLD did not significantly alter the apparent systemic clearance of theophylline, and that was also true when the three exsmokers were excluded, eg, C1T = 0.93 ±0.15 ml/min/kg. Six of our patients showed a theophylline clearance of less than 1 ml/min/kg and after oxygen therapy, only one of them showed an increase; the values of the other five patients remained essentially unchanged. The study of the changes in the amounts of theophylline and its metabolites in urine (Table 3) does confirm that oxygen therapy did not affect the biotransformation of theophylline.
Figure 2. Distribution of individual values of theophylline systemic clearance, estimated in patients with COLD prior and during 02 therapy, according to the patients Pa02 and PaC02.
Figure 3. Relation of theophylline systemic clearance and PaC02 values in patients with COLD prior and during 02 therapy.
Table 3—Mean (± SEM) Recovery of Theophylline and Its Metabolites in a Six Hour Urine Collection, Following a 4 mg/kg TV Dose of Theophylline in Ten Patients with COLD
|Before 02 Therapy||After 02 Therapy|
|Theophylline, mg||20.8±2.2||19.4 ±2.0|
|3-MX, mg||12.6±2.1||10.0± 1.9|
|1,3-DMU, mg||59.1 ±6.5||49.9 ±6.2|
|1-Mu, mg||33.9±4.2||27.3 ±3.4|
|Total, mg||126.5 ±13.3||106.7± 11.0|