Evaluation of the Influence of Hyoscine Butylbromide on the Oral Bioavailability of Lansoprazole in Healthy Adult Volunteers

The gastroesophageal reflux and/or peptic ulcer diseases are clinical conditions that occur usually accompanied of symptomatic pain. Lansoprazole, a proton pump inhibitor class drug is widely used in clinical practice for treatment of these diseases. However, its efficacy can be improved by combining with spasmolytic and/or visceral analgesic such as hyoscine butylbromide. Since hyoscine butylbromide is barely absorbed and exerts some local effects at gastrointestinal tract which may modify the absorption of lansoprazole, it is important to establish if there is a pharmacokinetic interaction after the oral concomitant administration of both drugs. For this objective, twenty-five subjects received under a crossover design an oral administration of lansoprazole (15 mg) plus placebo or a fixed-dose combination with hyoscine butiylbromide (15 mg + 10 mg, respectively). Plasma samples were obtained at different times during 10 hours. Lansoprazole plasma concentrations were determined by a high performance liquid chromatography method coupled to tandem mass spectrometry. Fixed-dose combination was well tolerated. Lansoprazole pharmacokinetic parameters were: Cmax 621.81 ± 212.79 and 450.38 ± 192.14 ng/mL;AUC0-t 1941.36 ± 845.57 and 1454.66 ± 757.28 ng·h/mL;tmax 2.83 ± 0.99 and 3.40 ± 1.82h;t1/2 1.35 ± 0.39 and 1.45 ± 0.51 h, for alone and combined fixed-dose formulation, respectively. Pharmacokinetic parameters were compared by analysis of variance and ratios of AUC0-t, Cmax and 90% confidence intervals obtained. Since confidence intervals exceed the 80% - 125% limits for these parameters, we conclude that there is a significantly pharmacokinetic interaction of lansoprazole when it is administered concomitantly with hyoscine butylbromide.

Pharmacokinetic investigation on nteraction between hydrophilic lithospermic acid B and lipophilic tanshinone IIA in rats:an experimental study

OBJECTIVE:To elucidate the interaction between hydrophilic lithospermic acid B and lipophilic tanshinone Ⅱ A in rats.METHODS:A reliable high-performance liquid chromatography method was adopted for simultaneous determination of lithospermic acid B and tanshinone Ⅱ A in rat plasma,through which the pharmacokinetic interaction between lithospermic acid B and tanshinone Ⅱ A by intravenous injection was investigated.RESULTS:The simultaneous intravenous injection of tanshinone Ⅱ A and lithospermic acid B significantly altered the pharmacokinetic parameters of both compounds when compared with the individual intravenous administration of each compound.The area under the concentration-time curve of tanshinone Ⅱ A and lithospermic acid B increased by 18.35 and 59.31%,respectively.The mean retention time of tanshinone Ⅱ A and lithospermic acid B increased,respectively,from 9.3 to 32.8 h and20.2 to 49.1 h.The concomitant use of tanshinoneⅡ A magnified the volume of distribution at steady state(V_(ss)) and time for the drug in the plasma to reduce the highest concentration by half(t_(1/2)) of lithospermic acid B,while at the same time the V_(ss) and t_(1/2)of tanshinone Ⅱ A changed significantly in the presence of lithospermic acid B.CONCLUSION:Lithospermic acid B and tanshinone D A interact with each other following simultaneous intravenous injection in rats and this observation may expand the clinical use of Danshen(Radix Salviae Miltiorrhizae).

Pharmacokinetic interaction of Acacia catechu with CYP1A substrate theophylline in rabbits

OBJECTIVE:To investigate the effect of black catechu(BC) on the pharmacokinetics of theophylline(CYP1A2 substrate,with narrow therapeutic index)in rabbits.METHODS:In the present investigation the effect of BC on the pharmacokinetics of theophylline,a CYP1A2 substrate was determined.In the study,BC(264 mg/kg,p.o.) or saline(control group) was given to rabbits for 7 consecutive days and on the 8^(th)day theophylline(16 mg/kg) was administered orally one hour after BC or saline treatment.Blood samples were withdrawn at different time intervals(0.5,1,1.5,2,3,4,6,8,12,24 and 36 h) from the marginal ear vein.RESULTS:The pretreatment of rabbits with BC resulted in a significant increase in maximum blood concentration,time of peak concentration and area under the concentration time profile curve until last observation which was about 41.32%,35.71%and 15.03%,respectively.While decreases in clearance,volume of distribution,and half-life were observed.It is suggested that BC pretreatment decreases the CYP1 A metabolic activity leading to increase in bioavailability and decrease in oral clearance of theophylline,which may be due to inhibition of CYP1 A.CONCLUSION:BC can significantly alter theophylline pharmacokinetics in vivo possibly due to inhibition of CYP1 A and P-glycoprotein activity.Based on these results,precaution should be exercised when administering BC with CYP1 A substrate.