Abstract:Following intravenous bolus injection of theophylline 2.37.10−4mol kg−1to guinea pigs (administered as aminophylline 52.0 mg kg−1), the elimination of the dose was more rapid in a group of 8 guinea pigs that had received theophylline 2.02 · 10−4mol kg−1(aminophylline 44.3 mg kg−1) intraperitoneally twice daily for 12 days prior to the experiment than in a group of 10 non‐pretreated guinea pigs of the same age. The difference was statistically significant in Student's t‐test (P<0.02). The mean values in the group of pretreated animals were: kel0.00457 min.−1, β 0.00296 min.−1, clearance 2.04 ml kg−1min.−1, Vdβ693 ml kg−1. By way of comparison, the values obtained in non‐pretreated guinea pigs were: kel0.00293 min.−1, β 0.00198 min.−1, clearance 1.50 ml kg−1min.−1, Vdβ757 ml kg−1. This result suggests enzyme induction to occur. The pharmacologically active theophylline metabolite 3‐methylxanthine did not accumulate in the plasma during the long‐term theophylline administration. The general plasma concentration level was 0–1.8.10−8mol ml−1(0–3 μg ml−1). In 5 percent of the samples were detected concentrations in the range 1.8 · 10−8‐7.2 · 10