| BackgroudsFor the past many years,pharmaceutical workers have researched some tablets that contain the same chemical compositions and contents,and found that the bioavailability of these tablets was different.For clinical application,the same dosage form and type drugs of different manufacturers were also different,and even the different batch number drugs of the same manufacturer were different for bioavailability.The more much and sharpen drug absorption resulted in that the peak value of concentration-versus-time curve was higher and the peak time was earlier. The difference of the excipient resulted in the change of bioavailability.This explain that the bioavailability can not completely measure clinical practical application effect. It is essential to investigate the bioequivalence of the drugs.Investigation of the bioequivalence was an important methods that evaluate drug quality.Pharmacokinetic parameters(the area under the plasma concentration verus time curve,peak concentration,peak time) were calculated to evaluate the bioequivalence of the drugs.Accordingly,experimental design and evaluate of the bioequivalence were important content of reporting and approval of new drugs especially homogeneity equivalent drugs.Investigating bioavailability and bioequivalence of the drugs was an important jobs in terms of drug research and development managementNimodipine(Nimo) belongs to 1,4-dihiobenzene hydrogen pyridine classes of calcium channel blockers,Its pharmacological mechanism is effectively adjust cell calcium level,to maintain the normal physiology function.The role of cerebral, particularly prominent central nervous system with specific receptors,inhibit vascular smooth muscle cells of calcium ions in the flow,which can effectively prevent the treatment of caused by subarachnoid hemorrhage of cerebral vasospasm caused damage brain ischemia.Mainly used in clinical ischemic cerebrovascular disease,migraine, cerebral vasospasm caused by subarachnoid hemorrhage,sudden deafness,improving old memory loss and preventing alzheimer's disease.Delayed release preparation was adopted latest technique and change the progress of drug absorption and release,therefore,it is essential to undertake bioavailability research to confirm the feature of delayed release.The bioequivalency research of delayed release preparation will execute repeated dose study except to single dose study.Practically,the clinical application of delayed release preparation was not only single dosage and drug was repeatedly apply few days or many days.Therefore, investigating the bioequivalence of blood drug level of steady state was an importantly practical significance.Objectives1,To investigate the bioavailability and correlative pharmacokinetic parameters of the experimental and contrastive nimodipine sustain-released tablets after single oral dose and multi oral doses study.2,To evaluate the bioequivalence of the experimental and contrastive nimodipine sustain-released tablets after single oral dose and multi oral doses study.The aim was to provide theoretical base for clinical application of nimodipine sustain-released tablets.MethodsThe experimental preparation is specific oral administration sustained release preparation.According to the related regulations of《guidance principle for bioavailability and bioequivalence of chemicals preparation in the human body》(2005), this research is executed on condition that single and multioral doses.1,Eighteen healthy male volunteers were divided into two groups by an open, randomized two period crossover with seven days washout intervals.The research was undertaked after oral administration 60 mg nimodipine sustained release medication.2,After single oral administration drugs,after washout period,two grougs healthy male volunteers oral administration 60 mg nimodipine sustained release medication, respectively,one time daily,in series for four days.After authenticated blood drug level have achieved steady state,the research for bioequivalence was undertaked. ResultsThe main pharmacokinetic parameters of experimented and contrastive nimodipine sustain-released tablets obtained from single oral dose study were as following:Tmax were 2.97±0.88 h and 2.89±0.76 h,Cmax were 31.00±9.13μg·L-1and 32.13±10.00μg·L-1,T1/2 were 2.70±0.48 h and 2.85±0.81 h,MRT0-t were 4.71±0.24 h and 4.93±0.27 h respectively,MRT0-∞ were 5.52±0.52 h和5.94±0.91 h respectively; AUC0-t were(177.64±42.43μg·h·L-1 and 186.41±49.37μg·h·L-1,AUC0-∞ were 190.20±45.22μg·h·L-1 and 204.34±54.46μg·h·L-1,respectively.The relative bioavailability of nimodipine was 99.18±25.08%.The steady-state pharmacokinetic parameters as following:Tmax were 2.36±0.70 h and 2.61±0.76 h,Css max were 42.37±6.34μg·L-1 and 45.66±6.88μg·L-1,Css min 13.37±3.37μg·L-1 and 13.51±2.55μg·L-1,Css av were 24.61±3.69μg·L-1 and 25.49±3.45μg·L-1,MRT0-t were 4.92±0.23 h and 4.95±0.29 h,MRT0-∞ were 7.76±1.35 h和7.24±0.86 h,respectively;AUCss 0-t were 295.27±44.32和305.91±41.38,AUCss 0-∞ were 370.27±53.69μg·h·L-1 and 69.75±43.54μg·h·L-1,DF were 118.57±21.09 and 127.22±27.54 respectively.The relative bioavailability of DSSR was 97.11±12.25%.ConclusionsTest product:nimodipine sustained release tablet(manufacture in Shanxi yabao pharmaceutical limited company,specification:60 mg/tablet;batch number:061001) and reference product:nimodipine sustained release tablet(made in Qilu pharmaceutical limited company);specification:60 mg/tablet;batch number:611003KG; Approved by the state number:H10950173),are bioequivalent in healthy volunteers. |
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