| Objective:To establish an flame atomic absorption spectrometry for the determination of Zinc in human plasma. Pharmacokinetics research about its’ single and multiple dosing and pharmaceutical preparations were done in health volunteer. Its dynamic changes including absorption、distribution and elimination were known from health volunteers.Methods:1. single-dosing pharmacokinetics research12health volunteers were separated in3teams and every team include2females and2males. Every team takes orally different dosage (75mg、150mg、300mg) in different experiment cycle and elution period is1week. Gathering venous blood volume is4ml in different time after dosage. Atomic absorption photometric method was used for the determination of Polaprezinc Granules in human plasma. DAS Ver2.1.1and SPSS Ver16.0were used to compute and analyze main pharmacokinetics parameters.2. pharmacokinetics research about food12health volunteers were separated in2teams and every team include3females and3males. Every volunteer takes75mg drug on an empty stomach or after taking food and elution period is1week. Gathering venous blood volume is4ml in different time after dosage. Atomic absorption photometric method was used for the determination of Polaprezinc Granules in human plasma. DAS Ver2.1.1and SPSS Ver16.0were used to compute and analyze main pharmacokinetics parameters.3.Multiple-dosing pharmacokinetics research6female and6male volunteers take75mg for twice in one day and successive administration for13times. Gathering venous blood volume is4ml in the eleventh、 the twelfth、the thirteenth before dosage and different time after dosage. Atomic absorption photometric method in human plasma was used for the determination of Polaprezinc Granules. DAS Ver2.1.1and SPSS Ver16.0were used to compute and analyze main pharmacokinetics parameters.Results:1. single-dosing pharmacokinetics researchPharmacokinetics parameters were estimated by non-compartment model. The main pharmacokinetics parameters after single-dosage75mg,150mg,300mg on an empty stomach were list as follow:Tmax (1.52±0.43、1.71±0.54、1.83±0.74h); Cmax (1.76±0.32、2.23±0.48、2.83±0.60mg·L-1); AUC0'12(8.78±1.57、11.42±1.90、14.24±3.78mg·L-1*h); AUC0'∞,(10.08±2.22、12.42±2.23、15.67±4.65mg·L-1*h); V/F (41.03±10.69、53.47±19.70、90.17±34.18L); T1/2(3.88±1.59、3.02±1.05、3.06±0.82h);CL/F(7.86±2.13、2.47±2.43、20.68±5.85L·h-1);MRT0'12(4.29±0.38、4.32±0.29、4.22±0.25h).Analysis of variance among main pharmacokinetics parameters is shown as follow:the difference of Tmax、T1/2and MRT0'12between different dosage have no significant meaning (p>0.05). The parameters of AUC0'12、AUC0'∞、Cmax、 V/F and CL/F between different dosage have significant meaning (p<0.01). Linear regression analysis shown AUC0'12、AUC0'∞、Cmax、V/F and CL/F have linear relationship with dosage.Independent sample t-test between AUC0'12、AUC0'∞、Cmax、Tmax、T1/2、 MRT0'12、V/F、CL/F show there have no significant meaning in different sexuality.2. pharmacokinetics research about foodPharmacokinetics parameters were estimated by non-compartment model. The main pharmacokinetics parameters after single-dosage on an empty stomach and taking high fat and high energy food were as follow:Tmax (1.81±0.58'1.48±1.34h);Cmax (2.13±0.32'1.03±0.24mg·L-1); AUC0'12(12.38±1.48'8.76±2.55mg·L-1*h); AUC0'∞(14.61±2.53'31.40±25.36mg·L-1*h); V/F (30.88±6.51'80.22±25.26L); T1/2(4.18±1.15'22.22±18.13h); CL/F (5.26±0.79'4.35±3.17L·h-1); MRT0'12(4.63±0.27'5.49±0.41h)。3. Multiple-dosing pharmacokinetics researchPharmacokinetics parameters were estimated by non-compartment model. After successive administration for13times, the main pharmacokinetics parameters were get as follow:Tmax (1.44±0.57h), Cmax (2.32±0.56mg·L-1), AUC0'12(13.61±2.86mg·L-1*h), AUC0'∞(16.27±3.57mg·L-1*h), V/F (29.81±7.24L), T1/2(4.44±1.19h), CL/F (4.89±1.42L·h-1), MRT0'12(4.68±0.31h), Cmin(1.03±0.23mg·L-1), C,v(1.13±0.24mg·L-1), DF (1.12±0.21), R (1.10±0.87). Conclusion:The flame atomic absorption spectrometry to determine Zinc in human plasma is specific,sensitive, steady.The method can be used to pharmacokinetics study of polaprezinc granules in healthy volunteers. After single-dosage75mg、150mg、300mg on an empty stomach, the difference of Tmax、T1/2and MRTo'12between different dosage have no significant meaning. Linear regression analysis shown AUC0'12、AUC0'∞、Cmax、V/F and CL/F have linear relationship with dosage.Independent sample t-test is shown:Cmax、AUC0'12、MRT0'12、and V/F have significant meaning.This means taking food can decrease the absorption of zinc.Independent sample t-test between AUC0'12、AUC0'∞、Cmax、Tmax、T1/2、 MRT0'12、V/F、CL/F shown single and multiple dosage teams have no significant meaning. Pharmacokinetics parameters between single and multiple dosage have no significant meaning,due to multiple dosage have no cumulation in body. |
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