1.Progress on pharmacokinetic studies of therapeutic monoclonal antibodies
Jianjun GUO ; Lili WANG ; Qi ZHANG ; Aobo ZHANG ; Jing ZHU ; Yongyue ZHAO ; Bingxu ZHANG ; Haizhi BU
Chinese Pharmacological Bulletin 2016;(2):172-176
Monoclonal antibody ( mAb ) represents a class of therapeutics experienced dramatic development over the past 30 years. Because of the tremendous differences in physicochemical and biological properties between mAbs and small molecules, the mAb therapeutics significantly differ from the chemical drugs in pharmacokinetic characteristics and underlying mechanisms. Full understanding of those characteristics and mechanisms may efficiently guide the screening and development of mAb medi-cines, and would well support their safety evaluation and clinical dosage regimen designing. This review is to summarize pharma-cokinetics and underlying mechanisms of mAbs from the aspects of absorption, distribution and elimination, as well as the ap-proaches for prediction of mAb pharmacokinetics in humans.
2.Pharmacokinetics of praziquantel injection in healthy buffaloes
Haifeng YANG ; Chuangang ZHU ; Yongjun LI ; Ke LU ; Hao LI ; Yaojun SHI ; Aobo ZHANG ; Guangfu LU ; Shijin BU
Chinese Journal of Schistosomiasis Control 2017;29(4):431-435
Objective To investigate the pharmacokinetics and relative bioavailability of praziquantel injection in buffaloes in contrast to praziquantel tablet. Methods A single oral administration of praziquantel tablet at a dose of 20 mg/kg or intramus-cular administration of praziquantel injection at a dose of 10 mg/kg was performed in six healthy adult buffalos according to a two-period crossover design. The praziquantel concentration in plasma was determined by a high performance liquid chromatography (HPLC)method. The pharmacokinetic parameters were calculated by non-compartmental analysis. Results The main pharma-cokinetic parameters of praziquantel tablet were as follows:Tmax=(0.60±0.29)h,Cmax=(0.57±0.37)μg/ml,T1/2β=(0.70±0.42) h,AUC=(0.80±0.70)(μg/ml)·h. The main pharmacokinetic parameters of praziquantel injection were as follows:Tmax=(0.65± 0.49)h,Cmax=(3.82 ± 1.17)μg/ml,T1/2β=(1.00 ± 0.73)h,AUC=(1.61 ± 0.89)(μg/ml)·h. The relative bioavailability of pra-ziquantel injection was 402.5%in contrast to praziquantel tablet. Conclusion The praziquantel injection has pharmacokinetic characteristics of rapid absorption,high bioavailability and extensive distribution,and the clinical recommended dosage of pra-ziquantel injection is 10 mg/kg.
3.Mid-term efficacy of surface knee prosthesis combined with bionic block in joint reconstruction after resection of giant cell tumor in proximal tibia
Aobo ZHANG ; Qing HAN ; Xiaonan WANG ; Wenbin LUO ; Hao CHEN ; Xin ZHAO ; Jincheng WANG
Chinese Journal of Orthopaedics 2023;43(10):659-664
A total of 6 patients were treated with surface knee joint prosthesis combined with 3D-printed customized bionic tibial block for reconstruction of bone defect after giant cell tumor (GCT) in proximal tibia (1 male and 5 females, aged 50, 40, 68, 53, 35, 42, respectively). 3 patients with primary and 3 patients with recurrence of GCT. After resection of the tumor, the bone defect was filled with 3D-printed block combined with surface knee prosthesis, the surrounding ligaments were reconstructed with microporous structure and artificial mesh. All cases were followed up for 60, 90, 60, 60, 75, and 50 months, respectively. During the follow-up, there was no local recurrence, no radiolucent lines around prosthesis, and no signs of loosening. The clinical scores of the American Knee Society Score (KSS) were 87, 92, 85, 90, 95 and 78. The functional scores were 70, 100, 70, 100, 100 and 80 respectively. Musculoskeletal Tumor Society Score (MSTS) were 27, 28, 26, 26, 26, 27, respectively. Surface knee prosthesis combined with bionic block can effectively fill the bone defect after resection of GCT in proximal tibia, achieve anatomical and functional reconstruction of knee joint.
4.Changes of brain oxygenated hemoglobin concentration in adolescent patients with depression under speech fluency task
Aobo CHENG ; Jiaqi FAN ; Lihui LIU ; Jinning LIU ; Lili ZHANG ; Hongying WANG ; Yunshu ZHANG ; Jianli YANG ; Keqing LI
Chinese Journal of Behavioral Medicine and Brain Science 2022;31(7):629-633
Objective:To explore the characteristics and differences of oxygenated hemoglobin responses in different brain regions in adolescent depressive disorder patients and healthy adolescents during speech fluency task based on functional near-infrared spectroscopy imaging.Methods:From March 2021 to June 2021, twenty-nine adolescents with depression(depressed group) and 26 healthy adolescents(normal group) were enrolled. The severity of depression was assessed by Hamilton depression scale, and the speech fluency task was performed by functional near-infrared spectroscopy brain imaging, and the relative concentrations of oxyhemoglobin in the prefrontal and bilateral temporal lobes were measured.SPSS 26.0 statistical software was used for data analysis, chi-square test was used for gender count data. The t-test was used for comparison of two groups. The measurement data that did not conform to normal distribution were compared between the two groups by Mann-Whitney U test. Results:In the speech fluency task, there was no significant difference in the concentration of oxygenated hemoglobin in prefrontal and left temporal between the depressed group and the normal group (both P>0.05); the oxygenated hemoglobin concentration in the right temporal lobe(-9.179(-22.231, 4.789)) of depressed group was significantly lower than that of the normal group (12.754(-9.438, 35.008)), and the difference was statistically significant ( U=538.00, P<0.05). The oxygenated hemoglobin concentration in right temporal lobe of depressed group had no correlation with the score of Hamilton depression rating scale ( r=0.092, P>0.05). Conclusion:The right temporal lobe function of adolescent depression patients is lower than that of healthy controls during speech fluency tasks, which provides a basis for study of the relationship between depression and some cognitive sensitivity impairment and the function of right temporal lobe.
5.Clinicopathological risk factors of retroperitoneal liposarcoma recurrence-free survival after surgical resection
Aobo ZHUANG ; Qian WU ; Jiongyuan WANG ; Jing XU ; Hanxing TONG ; Yong ZHANG ; Weiqi LU
Chinese Journal of General Surgery 2021;36(10):766-769
Objective:To explore the clinicopathological risk factors of retroperitoneal liposarcoma recurrence-free survival after surgical resection, and establish a prediction model based on clinicopathological risk factors.Methods:We conducted a retrospective analysis for retroperitoneal liposarcoma patients undergoing surgical resection at Department of General Surgery, Shanghai Public Health Clinical Center, Zhongshan Hospital (South), Fudan University, during Jul 2014 and Jun 2020. The clinical and pathological data were collected. Univariate and multivariate analysis were used to select independent risk factors.Result:A total of 271 patients were included, and 127 (46.9%) were recurred. In the recurrence group, more patients were assessed as recurrent disease ( χ2=15.289, P<0.05), the proportion of tumors invading organs was higher ( χ2=10.123, P<0.05), and FNCLCC graded higher ( χ2=7.650, P<0.05). The median follow-up time for all patients was 25 months (1-58 months). The 1, 2, and 3-year recurrence-free survival rates were 61.4%, 40.3%, and 30.9%, respectively. Univariate analysis suggests that recurrent disease, organ invasion, poorly differentiated pathological types, and high FNCLCC grades are poor prognostic factors for postoperative recurrence (all P<0.05); Multivariate analysis showed that recurrent disease ( OR=3.135, 95% CI: 2.058-4.762, P<0.05), organ invasion ( OR=2.577, 95% CI: 1.214-5.464, P<0.05) and high FNCLCC grade ( P<0.05) is an independent prognostic factor for postoperative recurrence. Conclusion:Presentation status,FNCLCC grade and organ invasion were independent risk factors for retroperitoneal liposarcoma recurrence after surgery.
6.Analysis of pretreatment drug resistance and polymorphic sites in CRF08_BC strains among HIV-1 patients
Jiaxin ZHANG ; Jing HU ; Chang SONG ; Aobo DONG ; Miaomiao LI ; Yi FENG ; Yuhua RUAN ; Hui XING ; Lingjie LIAO
Chinese Journal of Microbiology and Immunology 2023;43(1):20-26
Objective:To investigate the prevalence of pretreatment drug resistance and the genetic polymorphism of CRF08_BC strains among HIV-1 patients in China.Methods:This cross-sectional survey involved the plasma samples of HIV patients in a national pretreatment HIV drug resistance survey conducted in 2018. RNA was extracted from the samples. The fragments containing protease and partial reverse transcriptase (PR/RT) regions were obtained and sequenced. Drug resistance was analyzed using Stanford HIVdb Program. Differences in polymorphic mutations between drug-resistant and non-drug-resistant HIV-1 strains were analyzed by Chi-square test or Fisher′s exact test. The association between drug-resistant and polymorphic mutations was evaluated using CorMut R package. Molecular transmission networks were constructed using HIV-TRACE software. Results:Totally 465 partial pol sequences were obtained from individuals with CRF08_BC infection in 25 provinces and cities. The total pretreatment drug resistance rate was 17.8% (83/465). The pretreatment drug resistance rates to non-nucleoside reverse transcriptase inhibitors (NNRTIs), nucleoside reverse transcriptase inhibitors (NRTIs) and protease inhibitors (PIs) were 16.6% (77/465), 1.1% (5/465) and 0.9% (4/465), respectively. The resistance rate to rilpivirine (RPV) was the highest (15.7%, 73/465). The most common mutation was E138A (11.6%, 54/465). There were six polymorphic mutations (S162C, K102Q, T200A, V179E, I202V, T200M) that co-variated with E138A. The molecular transmission network showed that patients infected with CRF08_BC strains carrying the resistant mutations at position E138 mainly gathered in clusters in Yunnan and Sichuan, and the highest degree of connection was in Lincang, Yunnan. Conclusions:In China, HIV-1 CRF08_BC-infected patients showed a high rate of pretreatment resistance to one of the second-generation NNRTIs, namely RPV. Further researches were warranted to evaluate the impacts of co-mutations of the E138A mutation and polymorphic sites on HIV resistance and replicative capacity.
7.Association of nocturnal serum cortisol level with diabetic microvascular complications in overweight/obese type 2 diabetic patients
Aobo FU ; Yuting XIE ; Binbin HE ; Lin YANG ; Shuoming LUO ; Jingjing ZHANG ; Yang XIAO ; Zhen WANG ; Wei LIU ; Qiong FENG ; Chen CHAO ; Yalin YANG ; Zhifeng SHENG ; Xin SU ; Yiqun PENG ; Xia LI ; Zhiguang ZHOU
Chinese Journal of Endocrinology and Metabolism 2018;34(10):834-838
Objective To explore the association of nocturnal serum cortisol levels with diabetic microvascular complications in overweight or obese patients with type 2 diabetes mellitus. Methods Serum cortisol levels of 316 overweight or obese type 2 diabetic patients were tested at midnight by the method of chemiluminescence. Diabetic microvascular complications were compared among various groups according to nocturnal serum cortisol levels. All the patients with nocturnal serum cortisol level > 50 nmol/L were asked to undergo overnight low-dose dexamethasone suppression test to rule out the possibility of subclincal Cushing's syndrome. The incidences of diabetic nephropathy ( DN ) , diabetic retinopathy ( DR ) , and diabetic peripheral neuropathy ( DPN ) were examined in all the patients. Results (1)The incidence of DN was gradually increased from 13.3%to 27.7%and 44.2%in patients with low, medium, and high cortisol level groups, showing a statistical difference among 3 groups ( P<0.05) . The incidences of DR in medium and high cortisol level groups were higher than that in low cortisol level group (40.6%and 47.7%vs 22.7%, both P<0.01). The incidence of DPN in high cortisol level group was higher as compared with low cortisol level group (60.5% vs 38.7%, P<0.01). (2) Nocturnal serum cortisol level in patients with diabetic microvascular complications was higher than that in patients without complications [ (136.87 ± 105.78 vs 97.55 ± 93.48) nmol/L, P<0.01]. Nocturnal serum cortisol level in patients with multiple diabetic microvascular complications was higher than that in patients with single diabetic microvascular complication [ (151.66±114.54vs117.69±90.26)nmol/L,P<0.05].(3)Singlefactorlogisticregressionanalysisshowedthat higher nocturnal serum cortisol level was a risk factor for diabetic microvascular complications in addition to female, age, longer diabetic duration, higher fasting plasma glucose ( FPG ) . Multivariate logistic regression analysis showed that higher nocturnal serum cortisol level was still a risk factor for diabetic microvascular complications after adjusted by diabetic duration, FPG, HbA1C, and the use of insulin (P=0.013). Conclusion Nocturnal serum cortisol level seems to be a risk factor for diabetic microvascular complications in overweight or obese patients with type 2 diabetes mellitus.