Theophylline‐terbutaline, a steady state study on possible pharmacokinetic interactions with special reference to chronopharmacokinetic aspects.

Abstract

1 The pharmacokinetic interaction of terbutaline and theophylline and chronopharmacokinetics of both drugs were studied in a three-way crossover study with repeated administration of terbutaline (Bricanyl Depot®) 7.5 mg twice daily, theophylline (TheoDurg) 300 mg twice daily alone or the combination of both for 7 days to 12 healthy volunteers (six male and six female). 2 After the morning dose on day 7, blood and urine were sampled for 12 h, and after the evening dose on day 7, blood and urine were sampled for 48 h. Theophylline concentrations in plasma and concentrations of unchanged drug and metabolites in urine were determined by two selective high performance liquid chromatography methods. Terbutaline concentrations in plasma and urine were measured with a gas chromatography-mass spectrometry method. Area under the plasma concentration-time curve, fluctuations in plasma concentration, mean residence time, elimination half-life, renal clearance as well as maximal, minimal and average plasma concentration at steady state were evaluated. 3 The addition of terbutaline to the repeated administration of theophylline lowered the relative bioavailability of theophylline by approximately 11% during the night interval, The rate of elimination of theophylline and mean residence time were influenced accordingly. No significant changes in excretion of the theophylline metabolites were observed, but the excretion of 3-methylxanthine was slightly reduced by the concomitant terbutaline administration. None of the observed changes should be of any clinical importance.4 The addition of theophylline did not influence any of the calculated pharmacokinetic parameters of terbutaline. 5 It can be concluded that no dosage adjustment is necessary when terbutaline and theophylline are given together. 6 Significant differences between the rates of absorption at day-time and at night-time were observed, both for theophylline and for terbutaline. The extent of absorption, however, was not different.

The novel combination of theophylline and bambuterol as a potential treatment of hypoxemia in humans

“…Our results also indicate that co-administration of theophylline and bambuterol result in lower systemic exposure and C max of both terbutaline and theophylline. While no evidence of interaction has been found in a previous study involving terbutaline (Jonkman et al 1988), such discrepancy can be explained by the fact that our study has, in comparison, produced higher plasma concentrations of terbutaline, thus its potential impact on theophylline metabolism was also higher.…”

Lack of Pharmacokinetic Interaction between Sumatriptan and Naproxen

“…Time-dependent effects of terbutaline on theophylline pharmacokinetics were reported by Jonkman et al 22 Addition of terbutaline resulted in no change in plasma levels of theophylline during daytime, but during nighttime, terbutaline lowered the steady-state plasma levels of theophylline. Accordingly, AUC of theophylline was lowered by 11% during nighttime.…”

Effect of Gender on Theophylline Clearance in the Asthmatic Acute Phase in Japanese Pediatric Patients

“…We excluded the data of patients who had complications and/or used drugs reported to affect theophylline clearance. Treatments with prednisolone, [24][25][26] oxygen supply, [27][28][29] or terbutaline, [30][31][32] were recognized as having insignificant effects in this study (Fig. 2).…”