注射用鼠抗人T淋巴细胞CD25抗原单克隆抗体在健康受试者体内药代动力学与药效学

目的 研究注射用鼠抗人T淋巴细胞CD25抗原单克隆抗体(WuTac)单次给药在中国健康受试者体内的药代动力学特征和药效学效应.方法 36名健康受试者,男女各半,随机分配到高,中,低(0.20,0.10,0.05 mg·kg-1)3个剂量组,通过酶联免疫吸附(ELISA)检测受试者血清中WuTac和人抗鼠抗体(HAMA)的浓度,评估该药物的药代动力学行为特征.通过流式细胞仪检测全血中T淋巴细胞表面CD25结合位点,计算白介-2受体(IL-2R)饱和度,对本品的药效学做出评判.结果 高,中,低3个剂量组的主要药代动力学参数如下:t1/2分别为(54.15±16.50),(54.39 ±21.17),(43.99±13.07)h;tmax分别为(2.50±2.02),(2.75 ±2.01),(2.08±2.06)h;Cmax分别为(2950.82±560.94),(1461.20±370.70),(608.95±81.66)μg·L-1;AUC0-t分别为(8881.90±2188.10),(3711.00±1146.10),(1158.20±306.20)μg·L-1·d;AUC0-∞分别为(9458.80±2547.80),(4115.40±1208.40),(1269.70±310.40)μg·L-1·d.高,中,低3个剂量组单次恒速滴注停药1 h后,均能饱和T细胞白介2受体(IL-2R)相应结合位点,饱和度达96%以上,维持饱和3 d以上.结论 本品在中国健康人体起效迅速,疗效持久.单次给药耐受性良好,呈线性药代动力学特征.     

注射用鼠抗人T淋巴细胞CD25抗原单克隆抗体在肾移植患者体内的药动学与药效学

目的研究注射用鼠抗人T淋巴细胞CD25抗原单克隆抗体(WuTac)在肾移植患者体内的药动学和药效学。方法 16名肾移植患者随机分配到低、高(0.2,0.1 mg.kg-1)2个剂量组,用酶联免疫吸附法检测受试者血清中WuTac和人抗鼠抗体(HAMA)的浓度,评估该药物的药动学行为特征;通过流式细胞仪,检测全血中T细胞表面CD25结合情况,评判其药效学。结果低、高2个剂量组的主要药动学参数:T1/2分别为(51.41±16.24)(,59.53±24.96)h;AUCss分别为(2.28±0.35)(,5.13±1.53)mg.d.L-1;AUC0-t分别为(8.63±1.87)(,19.16±9.01)mg.d.L-1;AUC0-∞分别为(9.11±2.28)(,21.03±10.88)mg.d.L-1;Cmax分别为(3.27±0.53)(,8.36±1.92)mg.L-1;Tmax分别为(2.50±0.76)(,2.47±1.06)h。2组多次恒速滴注停药后,均能饱和T细胞白介2受体(IL-2R)相应结合位点。结论本品在中国肾移植患者起效迅速,疗效持久。多次给药耐受性良好,WuTac在0.1～0.2 mg...     

Pharmacokinetics of recombinant human interleukin-11 (rhIL-11) in healthy male subjects

Aims To study the pharmacokinetics of recombinant human interleukin-11 (rhIL-11) in healthy male volunteers following subcutaneous (s.c.) and intravenous (i.v.) administration.
Methods RhIL-11 was infused intravenously at 10–50  μg  kg⁻¹ for 1 or 3  h, or administered subcutaneously at 3–50  μg  kg⁻¹ to volunteers. RhIL-11 was also administered at 3  μg  kg⁻¹ s.c. once daily for 7 days. Plasma and urinary concentrations were measured by enzyme-linked immunosorbent assay (ELISA).
Results RhIL-11 showed linear pharmacokinetics after both intravenous infusion and s.c. administration. Comparison of t _1/2 and MRT values after i.v. administration with those after s.c. administration indicated that rhIL-11 pharmacokinetics after s.c. administration were absorption rate-limited. Bioavailability after s.c. administration was about 65%. Since RhIL-11 was not detected in urine after a single 50  μg  kg⁻¹ s.c. dose, rhIL-11 was considered to be eliminated by metabolism. There was no significant change in the pharmacokinetic profile of rhIL-11 following repeated s.c. administration.
Conclusions RhIL-11 demonstrated linear pharmacokinetics at these dose ranges after single and repeated s.c. administration or constant-rate i.v. infusion in healthy volunteers.     

Pharmacokinetics and pharmacodynamics of PF-05231023, a novel long-acting FGF21 mimetic,in a first-in-human study

Aims

The aim of the present study was to evaluate the pharmacokinetics/pharmacodynamics (PK/PD), safety and tolerability of single intravenous (IV) doses of PF-05231023, a long acting fibroblast growth factor 21 (FGF21) analogue being developed for the treatment of type 2 diabetes mellitus (T2DM).

Methods

T2DM subjects (glycosylated haemoglobin: 7.0–10.5%; on stable metformin therapy and/or diet and exercise) were randomized to receive a single dose of placebo or PF-05231023 (0.5–200 mg). Safety evaluations were performed up to 14 days after dosing. PK and PD endpoints were measured and a PK/PD model was developed for triglyceride – an early marker of drug activity.

Results

No antidrug antibody or serious adverse events (AEs) were observed. The most frequent AEs were gastrointestinal but were generally mild. Plasma PF-05231023 levels peaked immediately post-IV dosing, with mean terminal half-lives of 6.5–7.7 h and 66.5– 96.6 h for intact C- and N-termini, respectively. Intact C-terminus exposures increased proportionally with increasing dose, whereas N-terminus exposures appeared to trend higher than dose-proportionally. Although no apparent effect on plasma glucose was seen, dose-dependent decreases in triglyceride were observed, with a maximum reduction of 48.5 ± 10.0% (mean ± standard deviation) for the 200 mg dose compared with a reduction of 19.1 ± 26.4% for placebo, demonstrating proof of pharmacology. Moreover, a reduction in total cholesterol and low-density lipoprotein cholesterol and an increase in high-density lipoprotein cholesterol were observed in the high-dose groups.

Conclusions

Single IV doses of PF-05231023 up to 200 mg were generally safe and well tolerated by subjects with T2DM. The observed early sign of pharmacology supports further clinical testing of PF-05231023 upon repeated administration.     

尿激酶-抗尿激酶抗纤维蛋白双特异单克隆抗体复合物在小鼠体内的药物动力学

目的研究尿激酶-抗尿激酶抗纤维蛋白双特异单克隆抗体复合物(UK-BI9E11)在小鼠体内的药物动力学特征.方法小鼠ivUK-BI9E11后,用平板法测定不同时间小鼠血清中尿激酶的活性,并计算其药物动力学参数.结果本方法重现性好,灵敏度高;UK-BI9E11在血中的经时变化过程符合二室模型.与注射尿激酶所得的药物动力学参数相比,注射UK-BI9E11后的T1/2α、T1/2β均延长.结论BI9E11与UK形成复合物后,可延长尿激酶在血中的T1/2α、T1/2β.     

碱性成纤维细胞生长因子单克隆抗体在小鼠体内药代动力学研究

目的研究碱性成纤维细胞生长因子单克隆抗体(basic fibroblast growth factor monoclonal antibody,bFGF-mAb)在小鼠体内的药代动力学特征。方法首先制备bF-GF-mAb并纯化,然后用氯胺T法制备125I-bFGF-mAb,γ放射免疫计数仪检测三氯醋酸(TCA)沉淀前后血浆、组织的放射性计数,用3P97软件拟合药代动力学房室模型,并计算相应药代动力学参数。结果氯胺T法制备的125I-bFGF-mAb,其放化纯度≥98%,TCA沉淀率(90.8±10.2)%。T12α为0.1～0.2 h,T12β为1.05～1.84 h和T 12γ为81.6～90.3 h。125 I-bFGF-mAb在小鼠的心、肝、肺等组织器官中有较高的放射性计数,在脑和眼中放射性计数较低。结论 125I-bFGF-mAb的药代动力学符合三室模型,且具有组织分布特异性。     

Pharmacokinetics and pharmacodynamics of the vasopeptidase inhibitor,omapatrilat in healthy subjects

AIMS: To determine the pharmacokinetics, pharmacodynamics and tolerability of omapatrilat, a vasopeptidase inhibitor, in healthy subjects. METHODS: The effects of oral omapatrilat were evaluated in healthy men in two double-blind, placebo-controlled, dose-escalation trials. In a single-dose study, subjects received omapatrilat in doses of 2.5, 7.5, 25, 50, 125, 250, or 500 mg. In a multiple-dose study, subjects received doses of 10, 25, 50, 75, or 125 mg daily for 10 days. RESULTS: In the multiple-dose study, peak plasma concentrations (Cmax = 10-895 ng ml(-1); tmax = 0.5-2 h) of omapatrilat were attained rapidly. Omapatrilat exhibited a long effective half-life (14-19 h), attaining steady state in 3-4 days. In the single-dose study, Cmax (1-1009 ng ml(-1)) and AUC(0,t) (0.4-1891 ng ml(-1) h) were linear but not dose proportional. In the multiple-dose study, based on weighted least-squares linear regression analyses vs dose, Cmax but not AUC(0,t) was linear at the lower doses on day 10. The lowest dose of omapatrilat (2.5 mg) almost completely inhibited (> 97%) serum angiotensin converting enzyme activity at 2 h after dosing. In the multiple dose study, angiotensin converting enzyme activity was inhibited by more than 80% 24 h after all doses of omapatrilat. Inhibition of neutral endopeptidase activity was shown by increases in the daily urinary excretion of atrial natriuretic peptide and cyclic guanosine monophosphate at doses of more than 7.5 and 25 mg, respectively. In the single dose study, omapatrilat increased the daily urinary excretion of atrial natriuretic peptide dose-dependently from 10.8 +/- 4.1 (+/- SD) ng 24 h(-1) in the placebo group to 60.0 +/- 18.2 ng 24 h(-1) in the 500 mg group. Omapatrilat did not affect sodium and potassium excretion or urinary volume. Compared with placebo, omapatrilat produced a decrease in mean arterial pressure at 3 h after all doses in both the single- and multiple-dose studies. CONCLUSIONS: Omapatrilat was generally well tolerated. The pharmacokinetic and pharmacodynamic effects of omapatrilat are consistent with once-daily dosing.     

Pharmacokinetics, pharmacodynamics, and safety of microencapsulated octreotide acetate in healthy subjects

The pharmacokinetics, pharmacodynamics, and safety of the marketed formulation of microencapsulated octreotide acetate were evaluated in an open-label study in 22 healthy cholecystectomized subjects. Each subject received a single 30 mg dose of microencapsulated octreotide acetate intramuscularly (i.m.). Concentrations of octreotide, growth hormone (GH), insulin-like growth factor binding protein 3 (IGFBP-3), and insulin-like growth factor 1 (IGF-1) as well as clinical safety were evaluated over a period of 112 days (16 weeks). After the injection, mean serum octreotide concentration initially increased rapidly, reached the maximum (Cmax, day 1 = 0.96 +/- 0.25 ng/ml) approximately 1.5 hours after dosing, and declined thereafter until 24 hours postdose (Cmin, 24 h = 0.088 +/- 0.093 ng/ml). The octreotide concentration then increased and started a sustained release from day 7 onward. Plateau concentrations were maintained through day 70 and gradually declined to below the lower limit of quantification (LLOQ) by day 112. The plateau height (Cplateau (2-112d, 60%)) was 1.68 +/- 0.88 ng/ml, and the duration (delta plateau, 60%) was 30.2 +/- 15.7 days. The integrated concentration-time curve, AUC0-112d, was 2819 +/- 782 (ng.h/ml), and the apparent half-life (t1/2) was 169 hours. To assess the variability, the drug concentrations were determined hourly for 8 hours on day 28, and the mean octreotide concentration, Cavg, day 28' was 1.55 +/- 1.26 ng/ml. The suppression of IGF-1 was statistically significant compared to the baseline (p < 0.05) through day 63; however, there were no appreciable changes in GH and IGFBP-3 concentrations after a single injection of microencapsulated octreotide acetate. Simulation of a 28-day dose schedule suggested that steady-state octreotide concentrations would be reached by the third injection with steady-state concentrations about twofold greater than the first injection. There were no serious adverse events or clinically meaningful changes in vital signs, ECGs, or laboratory evaluations observed in this study, indicating that the 30 mg i.m. dose of microencapsulated octreotide acetate was well tolerated in this population.     

Pharmacokinetics and pharmacodynamics of a novel orally active angiotensin converting enzyme inhibitor (HOE 498) in healthy subjects

Summary The pharmacokinetics and pharmacodynamics of the angiotensin converting enzyme inhibitor HOE 498 were investigated in 10 healthy normotensive male subjects. Serum levels of the active metabolite M 1 (dicarboxylic acid) of HOE 498 were measured by HPLC up to 14 days after a single oral dose of 10 m g HOE 498. Peak serum concentration of M 1 between 5–50 ng/ml was observed 1.5–3.0 h after administration. The serum concentration-time curve of M 1 was polyphasic and exhibited a prolonged terminal phase with a half-life of approximately 110 h. Despite the long terminal half-life M 1 could not be detected in urine later than 72 h after administration. The activity of the angiotensin converting enzyme in plasma was completely suppressed for up to 12 h, and 72 h after dosing 50% inhibition of the enzyme was still observed.     

单抗类生物制品非临床安全性研究和评价的考虑要点

单抗（MAb）产品包括用杂交瘤制备的完整免疫球蛋白、免疫交联物以及从免疫球蛋白中获得的免疫球蛋白碎片和重组蛋白。单抗类生物制品与化学药物的非临床安全性研究和评价方法明显不同,原因在于前者的结构和生物学性质具有专一性和多样性,包括种属特异性、免疫原性和无法预料的多种组织亲和性。本文根据作者在单抗类生物制品非临床安全性研究和审评中的体会,介绍该类产品的非临床安全性研究和评价的考虑要点,以供研发者参考。     

Pharmacokinetics of oral cyclosporin a (Sandimmun) in healthy subjects

Summary Extensive pharmacokinetic (PK) profiles after oral dosing of 300 mg cyclosporin A (CsA) were determined in whole blood by radioimmunoassay (RIA) in 14 healthy male volunteers, using two-compartment models with either first order (M1) or zero order (M0) absorption. According to zero order absorption the mean of the following PK parameters was determined: terminal half-life=12.1±5.0 h, apparent volume of distribution at steady-state=5.6 ±2.1 l · kg^–1, apparent clearance=0.51±0.11 l · h^–1 · kg^–1. The time lag between drug ingestion and first blood level was short, 0.38±0.11 h. Drug absorption lasted for 2.8±1.6 h. The end of absorption was indicated in each individual by a sharp drop in blood levels.The observations support the assumption that CsA is absorbed in the upper part of the small intestine with a clear-cut termination (absorption window). This assumption may explain the high degree of variability in the bioavailability of CsA.This work was presented in abstract form at the British Pharmacological Society Meeting in Bath, UK, 9th–11th April 1986     

Pharmacokinetics and pharmacodynamics of single and multiple doses of the MAO-6 inhibitor lazabemide in healthy subjects

Aim The objectives of this study were to assess the tolerability, pharmacokinetics and pharmacodynamics of the reversible monoamine oxidase B (MAO-B) inhibitor, lazabemide, in healthy subjects.
Methods Single and multiple (1 week) twice daily oral doses (100–350 mg) of lazabemide were administered sequentially to five groups of six healthy male subjects in a placebo-controlled, double-blind design. Adverse events, vital signs, and clinical laboratory variables were recorded. Pharmacokinetic parameters of lazabemide were determined after single and multiple doses. Pharmacodynamics were assessed by determination of MAO-B activity in blood platelets and intravenous tyramine potentiation tests.
Results Lazabemide was well tolerated at all dose levels, causing no clinically relevant changes in vital signs or laboratory parameters. Headache was the most frequent adverse event at higher doses. Lazabemide was rapidly absorbed and eliminated by mixed linear and non-linear pathways. Only minor accumulation occurred upon multiple dosing and steady-state plasma concentrations were achieved on the third day. Lazabemide caused a rapid and reversible inhbition of MAO-B activity in platelets. The twice dady dosing regimen resulted in complete inhbition at all dose levels. The duration of complete inhbition was dose-dependent and ranged from 16 h with 100 mg to 36 h with 350 mg. The sensitivity to i.v. tyramine dd not change to a clinically relevant extent following single and multiple doses of lazabemide.
Conclusions The clinical pharmacology characteristics of lazabemide did not differ markedly after single and multiple oral doses. A dose regimen of lazebemide 100 mg twice daily is anticipated because it caused full and continuous MAO-B inhibition.     

Pharmacokinetics,pharmacodynamics and safety of LPM3480392 in two phase I clinical trials in healthy Chinese male subjects

Drugs for acute postoperative pain and breakthrough cancer pain are still urgent in clinical. LPM3480392 is a G-protein-biased ligand at the μ-opioid receptor and showed potent analgesia in nonclinical studies. Two phase I studies of LPM3480392 were conducted in healthy Chinese male volunteers to explore its tolerability, pharmacokinetics and pharmacodynamics under single ascending doses (Study I 0.1–3.0 mg, 30 min) and different infusion times (Study II, 0.6–1.0 mg, 2–15 min). There was one serious adverse event (AE) observed in Study II, and the rest AEs were mild or moderate in severity and resolved by the end of the study. Plasma LPM3480392 maximum concentration (C_max) (under lower infusion rate) and area under the plasma concentration-time curve (AUCs) were generally increased with dose. Moreover, LPM3480392 at a dose of 0.6 mg under a 2 min infusion rate elicited effective analgesia as the peak effect within 10–30 min, which was measured by cold pain test and pupillometry. These findings suggest that LPM3480392 could be a potential treatment for acute pain management.     

Pharmacokinetics and safety of golimumab, a fully human anti-TNF-alpha monoclonal antibody, in subjects with rheumatoid arthritis

Golimumab is a fully human antitumor necrosis factor alpha (TNF-alpha) monoclonal antibody that is being developed for intravenous and subcutaneous administration. To assess the pharmacokinetics and safety of the intravenous formulation of golimumab, 36 adult subjects with rheumatoid arthritis were randomly assigned to receive a single infusion of placebo or golimumab (0.1, 0.3, 1, 3, 6, or 10 mg/kg). Serum concentrations of golimumab were determined using a validated enzyme-linked immunosorbent assay method. In addition to the noncompartmental analysis and compartmental modeling, a population pharmacokinetics analysis using NONMEM was also conducted. Both the maximum serum concentration and the area under the serum concentrationtime curve appeared to increase in a dose-proportional manner. The median half-life ranged from 7 to 20 days. A 2-compartment population pharmacokinetic model adequately described the pharmacokinetics of golimumab. The following pharmacokinetic parameters (typical value [% coefficient of variation]) were estimated from the population pharmacokinetic model: clearance (CL: 0.40 [10.1%] L/d), volume of distribution in the central compartment (V(c): 3.07 [6.4%] L), intercompartmental clearance (Q: 0.42 [15.5%] L/d), and volume of distribution in the peripheral compartment (V(p): 3.68 [11.8%] L). Interindividual variability of the pharmacokinetic parameters was quantified for CL (44.3%), V(c) (25.5%), Q (44.6%), and V(p) (44.6%). Residual variability was estimated to be 15.0%. Body weight was found to be an important covariate on V(c). Golimumab was generally well tolerated. The pharmacokinetics of golimumab appeared to be linear over the dose range evaluated in this study.     

Pharmacokinetics and pharmacodynamics of ponesimod,a selective S1P1 receptor modulator,in the first-in-human study

Aims

This study investigated the tolerability, safety, pharmacokinetics and pharmacodynamics of ponesimod, a novel oral selective sphingosine-1-phosphate (S1P₁) receptor modulator in development for the treatment of auto-immune diseases.

Methods

This was a double-blind, placebo-controlled, ascending, single-dose study. Healthy male subjects received doses of 1–75 mg or placebo control.

Results

Ponesimod was well tolerated. Starting with a dose of 8 mg, transient asymptomatic reductions in heart rate were observed. Ponesimod pharmacokinetics were dose proportional. The median time to maximal concentration ranged from 2.0 to 4.0 h, and ponesimod was eliminated with a mean half-life varying between 21.7 and 33.4 h. Food had a minimal effect on ponesimod pharmacokinetics. Doses of ≥8 mg reduced total lymphocyte count in a dose-dependent manner. Lymphocyte counts returned to normal ranges within 96 h. A pharmacokinetic/pharmacodynamic model was developed that adequately described the observed effects of ponesimod on total lymphocyte counts.

Conclusions

Single doses of ponesimod up to and including 75 mg were well tolerated. The results of this ascending single-dose study indicate an immunomodulator potential for ponesimod and a pharmacokinetic/pharmacodynamic profile consistent with once-a-day dosing.     

Tolerability,pharmacokinetics and pharmacodynamics of CMAB001, an anti-CD11a antibody,in Chinese healthy volunteers and psoriatic patients

Aim:

To evaluate the pharmacokinetics (PK), pharmacodynamics (PD) and primary tolerability of an anti-CD11a monoclonal antibody (CMAB001) in Chinese healthy volunteers and psoriatic patients.

Methods:

Two open-label studies were conducted. One was a parallel-group, single-center, dose-escalation test, including 24 healthy adult volunteers from 18 to 45 years in age. All subjects randomly received a single subcutaneous injection dose of 0.5, 1.0 or 2.0 mg/kg. The other was a multiple-dose study: 10 adult psoriatic patients were administered weekly subcutaneous injections of 1.0 mg/kg for 7 weeks.

Results:

CMAB001 was well tolerated in the single- and multiple-dose studies. Slow absorption was observed in both studies. In the single-dose study, the concentration of CMAB001 reached its highest level 2 d later after the injection, and the C_max increased in an approximate dose-proportionate manner, while the area under curve (AUC) showed much greater than dose-proportionate increase. In the multiple-dose study, the steady-state serum concentration level was attained following the 4th injection.

Conclusion:

CMAB001 exhibited a nonlinear pharmacokinetic profile over the dose range from 0.5 to 2.0 mg/kg, and was well tolerated in healthy volunteers and psoriatic patients.     

普罗帕酮在健康受试者中的药动—药效学结合模型研究

目的:采用药动-药效结合模型观察普罗帕酮血浆浓度与心电图指标PR间期延长百分率的数量关系,并求算药效学参数。方法:选择健康汉族受试者10名,其中CYP2D6表型的快代谢型(EM)和中速代谢型(IM)各5名。受试者口服普罗帕酮片剂400mg,于给药后15h内抽取静脉血,并同步测定受试者PR间期。普罗帕酮浓度采用高效液相色谱分析法测定。采用CAPP软件对普罗帕酮血药浓度及PR间期延长百分率进行药动-药效结合模型计算。结果:10例健康志愿者的普罗帕酮血浆浓度与效应之间存在着滞后现象。经采用CAPP软件拟合数据,发现效应与浓度之间符合Sigmoid E_(max)模型。IM组的AUC(μg·h·L~(-1))明显高于EM组(5126±1030 vs2948±1230,P<0.05);相对应药效参数Ce_(50)IM组也比EM组大(P<0.05)。另外,效应曲线S线程度的参数γEM组大于IM组(P<0.05)。结论:CYP2D6遗传多态性不但对普罗帕酮的药动学有影响,而且对其药效学参数可能也有明显的影响。     

重组人白介素-11在人体内的药动学

目的研究皮下注射重组人白介素-11(rhIL-11)在人体内的药动学过程。方法24名健康志愿者,男女各半,随机分成2组。rhIL-11皮下注射剂量分别为5和7.5μg·kg~(-1),定时采血,用ELISA法测定不同时间血浆中rhIL-11的浓度。浓度-时间数据经3P97软件进行房室模型拟合,计算药动学参数。结果rhIL-112种剂量(5、7.5μg·kg~(-1))的主要药动学参数分别为:t_(max)(2.25±0.53)、(3.32±0.85)h;c_(max)(6.42±2.57)、(9.75±3.75)μg·L~(-1);T_(1/2)(4.03±1.24)、(4.42±1.32)h;AUC(52.68±14.06)、(102.73±36.26)μg·h·L~(-1)。体内过程符合一室模型。结论rhIL-11的药动学特征和参数可作为临床合理用药和制定给药方案的依据。     

单克隆抗体SZ-95亲和色谱纯化人血小板第4因子

目的用单克隆抗体亲和色谱从人血小板破碎液中纯化血小板第 4因子 (PF4 )。方法将单克隆抗体SZ 95 IgG与溴化氰活化的Sepharose 4B凝胶连接成亲和色谱柱SZ 95 IgG Sepharose 4B ,人血小板破碎液经此亲和色谱柱上样后 ,经洗脱获得PF4 ,采用 15 %SDS 聚丙烯酰胺凝胶电泳鉴定其纯度 ,用点印迹鉴定其免疫活性。结果SZ 95 Sepharose 4B亲和色谱柱的偶联率为 72 % ,每 1ml(约 1× 10 9个血小板 )血小板破碎液中可以纯化到PF4 18μg ,其相对分子量约为 12kD ,经点印迹显示与单抗SZ 95反应显带。结论用SZ 95 Sepharose 4B亲和色谱柱纯化的PF4产品得率高、纯度高、活性好