Pharmacokinetic parameters were calculated using conventional model independent methods by means of a nonlinear regression curve-fitting program. In order to calculate the apparent volume of distribution (Vd) and the apparent systemic clearance (C1T), we subtracted the area under theophylline plasma concentrations curve function of time (AUC) corresponding to the decline of theophylline plasma concentration at time 0 (calculated as from the total value of theophylline AUC (AUQmJ. Theophylline renal clearance (Cl*) was calculated by dividing the amount recovered in urine for six hours by the AUC©*. Theophylline metabolic clearance (C1M) was estimated from the equation CIT-C1R. this
The comparison of the effects of the two experimental conditions was carried out using a one-way analysis of variance. The minimal level of significance was p = 0.05.
As shown in Table 1, patients presented severe hypoxia and a mild hypercapnia secondary to obstructive lung disease. These showed considerable reduction in both the FEVi and the FVC, as well as in the FEV1/FVC percentage. After 48 hours of oxygen therapy, PaOz increased significantly; while PaCOz increased only slightly and the indices of ventilatory function showed no change at all.
Theophylline plasma concentrations showed a similar pattern before and after oxygen therapy in all subjects, whether they exhibited a low (n = 2) or a high (n = 8) level of theophylline at the beginning of the experiment. For convenience, the two groups were pooled (Fig 1). The AUC^ of theophylline was not modified by oxygen therapy (Table 2) and theophylline apparent volume of distribution remained constant. Theophylline systemic clearance increased in only four of the ten patients which resulted in only a slight increase in the average value. This finding was secondary to a slight increase in theophylline metabolic clearance, as renal clearance did not change with oxygen therapy. Theophylline half life was not affected by oxygen therapy.
Figure 1. Mean plasma concentrations of theophylline function of time, following a 4 mg/kg dosage, in patients with COLD. Vertical bars are SEM.
Table 2—Mean (± SEM) Distribution and Elimination Kinetic Parameters Following 4 mg/kg TV Dose of Theophylline in Ten Fatients with COLD
|Before 02 Therapy||After O, Therapy|
|AUCo*, |xg. min/ml||2709 ±410||2607 ±347|
|C1H, ml/min/kg||0.13 ±0.01||0.13 ±0.02|
|C1M, ml/min/kg||0.90 ±0.10||1.00±0.15|
|11/2, h||5.90 ±0.59||5.81 ±0.75|