OBJECTIVE To study the suitability of pharmacokinetic METHOD for evaluating the bioequivalence of different salbutamol metereddose inhalers (MDIs) by comparing the result with that of the pharmacodynamic method.METHODS A twotreatment,twoperiod,randomized,crossover design was adopted.Single dose of 400 μg salbutamol was given to patients with mild to moderate asthma.The blood samples were collected at 0,5,10,15,20 and 30 min after administration.The plasma concentrations of salbutamol were determined by HPLC.Two onesided t-tests and 90% confidence interval were used to evaluate the bioequivalence between the two products.The parameters of pulmonary function,FEV1.0,PEF,FVC,FEF25～75,and the safety parameter,heart rate (HR),were measured up to 6 h respectively.For all these parameters,comparisons were made by paired ttest.And those parameters with significant difference were selected for ANOVA.RESULTS The bioavailability parameters were obtained as following:cmax(1.22±0.73) and (0.98±0.52 ) ng·mL-1,tmax (0.21±0.09) and (0.26±0.08) h,AUC0～20 min (0.25±0.10) and (0.18±0.10) ng·h·mL-1,respectively.The relative bioavailability of the generic product was 63%.Two one sided t-tests and 90% CI (45%～88%) demonstrated that the two salbutamol MDIs were not bioequivalent.Ventolin produced stronger bronchodilating effect than the generic product.ANOVA on the key pharmacodynamic parameters showed that the two salbutamol MDIs were not equivalent.CONCLUSION S The bioequivalence evaluation result obtained from the pharmacokinetic method was in conformity with that from pharmacodynamic method,indicating that pharmacokinetic method was suitable for evaluating the bioequivalence of salbutamol MDIs.
Key words
salbutamol /
metered-dose inhaler /
bioequivalence /
pharmacokinetics /
pharmacodynamics
{{custom_keyword}} /
{{custom_sec.title}}
{{custom_sec.title}}
{{custom_sec.content}}
References
［1］Lipworth BJ.Pharmacokinetics of inhaled drugs ［J］.Br J Clin Pharmacol,1996,42 (6): 697.
［2］Lipworth BJ,Clark DJ.Comparative lung delivery of salbutamol given via Turbuhaler and Diskus dry powder inhaler devices ［J］.Eur J Clin Pharmacol,1997,53 (1):47.
［3］Lipworth BJ,Clark DJ.Lung delivery of nonCFC salbutamol and large volume plastic spacer devices compared with an open jet nebulizer ［J］.Br J Clin Pharmacol,1998,45 (2):160.
［4］Clark DJ,GordonSmith J.Lung bioavailability of generic and innovator salbutamol metered dose inhalers ［J］.Thorax,1996,51(3):325.
［5］Clark D,GordonSmith J,Clark G,et al.Lung bioavailability of generic and innovator formulations of inhaled salbutamol ［J］.Eur Resp J,1995,8 (Suppl 19): 259s.
［6］Newnham DM,McDevia DG,Lipworth BJ.Comparison of the extrapulmonary β-2-adrenoceptor responses and pharmacokinetics of salbutamol given by standard MDI and modified actuator device ［J］.Br J Clin Pharmacol,1993,36(5):445.
［7］Hindle M,Chrystyn H.Investigations of an optimal inhaler technique with the use of urinary salbutamol excretion as a measure of relative bioavailabilty to the lung ［J］.Thorax,1993,48(6):607.
［8］杜小莉，朱珠，傅强，等.沙丁胺醇气雾剂在健康受试者体内的药动学及生物利用度研究［J］.药学学报,2001,36(8):616.
［9］Pkemp James,Hill MR,Vaughan LM.Pilot study of bronchodilator response to inhaled albuterol delivered by MDI and a novel DPI ［J］.Ann Allergy Asthma Immunol,1997,79(4):322.
［10］〖STBZ〗〖KG1〗〖ZK(〗杜小莉,李大魁,朱珠.6种沙丁胺醇气雾剂的质量比较［J］.中国药学杂志,1999,34 (11):764.
［11］〖STBZ〗〖KG1〗〖ZK(〗Patnaik R,Lesko LJ,Chan K,et al.Bioequivalence assessment of generic drugs: an American point of view［J］.Eur J Drug Metab Pharmacokinet,1996,21(2):159.
［12］〖STBZ〗〖KG1〗〖ZK(〗Wong BJO,Hargreace FE.Bioequivalence of metereddose inhaled medicines［J］.J Allergy Clin Immunol,1993,92(3):373.
［13］〖STBZ〗〖KG1〗〖ZK(〗Spino Michael.Bioequivalence of generic aerosol bronchodilators:what are the issues［J］.CMAJ,1989,41(1):883.
［14］〖STBZ〗〖KG1〗〖ZK(〗Tweeddale M,Alexander F,McHardy GJR.Short term variability in FEV-1 and bronchodilator responsiveness in patients with obstructive ventilatory defects［J］.Thorax,1987,42(7):487.
［15］〖STBZ〗〖KG1〗〖ZK(〗Fuller RW,Hallett C,Dahl R.Assessing equivalence of inhaled drugs［J］.Respir Med,1995,89(8):525.
{{custom_fnGroup.title_en}}
Footnotes
{{custom_fn.content}}
