LACK OF INFLUENCE OF PANTOPRAZOLE ON THE DISPOSITION KINETICS OF THEOPHYLLINE IN MAN

The potential influence of pantoprazole (BY1023/SK&F96022), a newly de veloped selective inhibitor of the gastric H+,K+-ATPase, on therapeuti c serum theophylline concentrations was investigated in a crossover st udy in 8 healthy male volunteers (age 25-30 [median 27] years, body we ight 63-80 [median 68] kg). Steady-state serum theophylline concentrat ions were obtained by a two-step intravenous infusion scheme of approx imately 350 mg theophylline each over 0.5 h and subsequently over appr oximately 10 h, respectively. In the test period, 30 mg pantoprazole w ere injected over 2 min on 5 consecutive days and theophylline was inf used on day 4. In the reference period, placebo was administered i.v, on 2 consecutive days and theophylline on day 1. Serum pantoprazole co ncentrations were measured up to 12 h, serum theophylline concentratio ns up to 36 h. Pantoprazole was well tolerated with and without theoph ylline. There were no clinically relevant changes in blood pressure, h eart rate, ECG and routine clinical laboratory parameters. Primary cha racteristic for confirmative assessment of no interaction was the area under the concentration/time curve (AUG). Lack of interaction in the sense of equivalence was concluded both for theophylline (with and wit hout pantoprazole) and pantoprazole (with and without theophylline), a s the 90%-confidence intervals of the AUG-ratio test/reference were wi thin the equivalence range of 0.8 to 1.25. Further explorative analysi s of theophylline disposition kinetics revealed this inclusion also fo r clearance and volume of distribution, but not for the half-life. In the case of pantoprazole, the corresponding 90%-confidence intervals f or any of the secondary characteristics clearance, volume of distribut ion and half-life were within the above In conclusion, repeated once-d aily i.v. injections of 30 mg pantoprazole have no clinically relevant influence on steady-state theophylline serum concentrations, nor does theophylline at therapeutic serum concentrations influence the pantop razole disposition kinetics. Hence, in clinical practice theophylline and pantoprazole can be administered concomitantly without dose adjust ment.