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Lack of effect of co‐trimoxazole on the pharmacokinetics of orally administered theophylline
Author(s) -
Lo K. F.,
Nation R. L.,
Sansom L. N.
Publication year - 1989
Publication title -
biopharmaceutics and drug disposition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.419
H-Index - 58
eISSN - 1099-081X
pISSN - 0142-2782
DOI - 10.1002/bdd.2510100606
Subject(s) - theophylline , pharmacokinetics , volume of distribution , metabolite , crossover study , chemistry , pharmacology , oral administration , urinary system , area under the curve , absorption (acoustics) , urine , medicine , zoology , biochemistry , physics , alternative medicine , pathology , acoustics , placebo , biology
Eight healthy, male subjects participated in a balanced randomized crossover study to investigate the effect of a course of co‐trimoxazole (CT; combination of sulphamethoxazole 800 mg and trimethoprim 160 mg, twice daily for 5 days) on the pharmacokinetics and urinary metabolite profile of an orally administered dose of theophylline (TH). There were no significant differences ( p > 0·05) between the control and treatment phases with respect to any of the following pharmacokinetic parameters of TH: area under the plasma total TH concentration‐time curve; fraction unbound in plasma; area under the plasma unbound TH concentration‐time curve; terminal half‐life; apparent volume of distribution; apparent total plasma clearance and renal clearance. The urinary recoveries of 1‐methyluric acid, 1,3‐dimethyluric acid and of theophylline were not significantly different ( p > 0·05) between the two study phases. There was a significant difference ( p < 0·05), however, in the urinary recovery of 3‐methylxanthine (11·3 ± 2·6 per cent TH alone versus 13·9 ± 3·6 per cent TH‐CT) and in the total urinary recovery of TH and its metabolites (76·5 ± 8·2 per cent versus 85·3 ± 7·0 per cent), the latter finding suggesting that CT may have caused a small increase in the extent of TH absorption. The results of the study indicated that CT did not inhibit the biotransformation of TH.