Pharmacokinetics And Bioequivalence Of Diclofenac Sodium Sustain-released Tablet In Healthy Volunteers

BackgroudsFor the past many years, pharmaceutical worker have researched some tablets that contain same chemical compositions and contents, and found that the bioavailability of these tablets was different. For clinical application, the same dosage form and type drags 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 conccntration-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 was essential that investigated 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 management.Diclofenac sodium(DS) is a derivant of phenyl acetic acid that shows analgesic and eliminate inflammation properties in a variety of painful conditions. It is used in the treatment of rheumatic disorders and soft tissue injuries. Diclofenac sodium inhibits the cyclooxygenase enzyme and thus exerts its anti-inflammatory activity by inhibition of prostaglandin synthesis. Because of above-mentioned therapeutic effects of diclofenac sodium, diclofenac sodium was manufactured sustained release preparation and to puted into market.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 importantly practical significance.Objectives1,To investigate the bioavailability and correlative pharmacokinetic parameters of the experimental and contrastive diclofenac sodium sustain-released tablets after single oral dose and multi oral doses study.2,To evaluate the bioequivalence of the experimental and contrastive diclofenac sodium sustain-released tablets after single oral dose and multi oral doses study. The aim was to provide theoretical base for clinical application of diclofenac sodium 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 year), this research was executed on condition that single and multi oral 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 100 mg diclofenac sodium sustained release medication.2,After single oral administration drugs, after washout period, two grougs healthy male volunteers oral administration 100 mg diclofenac sodium 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 diclofenac sodium sustain-released tablets obtained from single oral dose study were as following: T_max were (2.08±0.65) and (2.11±0.78)h, C_max were (472.14±184.86) and (471.59±159.94)μg·L^-1, T_1/2 were (8.36±1.60) and (8.76±1.82)h, MRT were (13.05±2.68) and (13.72±3.16)h, respectively; AUC_0-t were (4521.17±2265.79) and (4589.69±2124.12)μg·L^-1, AUC_0-∞ were (5448.87±2850.13) and (5720.56±2992.74)μg·L^-1, respectively. The relative bioavailability of DSSR was (98.00±11.18)%. The steady-state pharmacokinetic parameters as following: T_max were (2.28±0.88) and (2.17±0.75)h, C_{ss max} were (595.77±224.95) and (575.93±203.01)μg·L^-1, C_{ss min} were (84.50±46.71) and (84.34±53.62)μg·L^-1, C_{ss av} were (257.64±134.41) and (261.09±129.89)μg·L^-1, T_1/2 were (9.88±2.82) and (9.56±2.63)h, MRT were (15.47±4.63) and (14.74±3.95)h, respectively; AUC_ss were (6183.36±3225.84) and (6266.25±3117.40)μg·L^-1, DF were 2.14±0.61 and 2.02±0.51, respectively. The relative bioavailability of DSSR was (98.25±5.82)%.ConclusionsTest product: diclofenac sodium sustained release tablet (manufacture in Shanxi yabao pharmaceutical limited company, specification: 100mg/ tablet; batch number: 061001) and reference product: diclofenac sodium sustained release tablet(made in Canada Apo-Diclo Tektronix limited company, trade name: Apo-Diclo; specification: 100mg/ tablet; batch number: GZ8303; imported commodity registration number: H20020541) are bioequivalent in healthy volunteers.