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To solve the problems in the course teaching of Pharmacokinetics and change the current situation of the course, a pharmacokinetic solution program based on Excel has been developed. The program, based on Excel, is the most widely used data processing software. The data processing and drawing functions of Excel are used and encapsulated as a program by Excel-VBA. The program is specially used in pharmacokinetic teaching, which includes 25 solution templates arranged according to the 5th edition of Biopharmaceutics and Pharmacokinetics, a textbook published by the People's Medical Publishing House Co., LTD. Each solution template includes six functional areas: operation setting area, data input area, data relationship display area, return parameter output area, pharmacokinetic parameter output area and chart area. In this course, the teaching content is reorganized. Starting from a case, the concept and knowledge of pharmacokinetics are taught by explaining how to apply the program to solve case problems. After years of practice, the teaching effect has been significantly improved.
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@#To investigate the in situ intestinal absorption characteristics and pharmacokinetic behavior of metformin-resveratrol compound water-in-oil nanoemulsion (MRCE) in rats, the in situ intestinal perfusion model was constructed in rats to study the intestinal absorption characteristics of MRCE in different intestinal segments. Male Sprague-Dawley rats were randomly divided into two groups. After intragastric administration of metformin and MRCE, blood was taken at a preset time point. The content of metformin in intestinal perfusion samples and blood samples at various time points was determined by HPLC. Plasma concentration-time profiles of free metformin and MRCE were calculated, and the main pharmacokinetic data were processed and analyzed by DAS 2.1.1 software. The absorption rate constant (Ka), the effective permeability (Peff) and the percentage of absorption (PA) of MRCE in each intestinal segment were significantly higher than those of metformin (P < 0.05). The area under the drug-time curve (AUC0-72 h), the half-life (t1/2) and mean residence time (MRT0-72 h) of MRCE were 1.68, 11.25 and 6.97 times of metformin, respectively (P < 0.01).The relative bioavailability of MRCE was 167.6%. The 90% confidence interval of AUC0-72 h was 156.9%-187.4%, which was not within the standard interval of bioequivalence. The intestinal absorption of MRCE was significantly better than that of free metformin; MRCE improved the oral bioavailability of metformin and was not bioequivalent to metformin.
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@#The aim of this study was to investigate the in vivo pharmacokinetic behavior characteristics and in situ intestinal absorption characteristics of the evodiamine lipidic nanoparticle in rats. Evodiamine lipidic nanoparticle was prepared by the solvent evaporation methods. The particle size and zeta potential of evodiamine lipidic nanoparticle were measured by dynamic light scattering analysis. Male SD rats were divided into two groups randomly. Each group was given single dose of evodiamine and evodiamine lipidic nanoparticle by gavage at evodiamine dose of 250 mg/kg,respectively. The blood samples were collected at scheduled time points. The content of evodiamine in plasma samples was determined by high performance liquid chromatography (HPLC) method. The main pharmacokinetic parameters of evodiamine and evodiamine lipidic nanoparticle were calculated using DAS 2.1.1 software. Moreover,the single-pass intestinal perfusion model was also established in rats to investigate the in situ intestinal absorption characteristics of evodiamine lipidic nanoparticle. The mean particle size and mean zeta potential of evodiamine lipidic nanoparticle were 180.10 nm and -17.90 mV,respectively. The area under the curve of evodiamine and evodiamine lipidic nanoparticle were (862.60±14.03) and (4084.31±17.21) μg/L·h,respectively,and the peak concentration were (163.40±13.27) and (616.90±21.04) μg/L,respectively. Moreover,the absorption of evodiamine lipidic nanoparticle was significantly higher than that of evodiamine in each segment of intestinal tract in rats (P<0.05). The absorption of evodiamine lipidic nanoparticle in colon was better than those of evodiamine lipidic nanoparticle in stomach,duodenum,jejunum and ileum. The absorption rate constant of evodiamine lipidic nanoparticle in stomach,duodenum,jejunum,ileum and colon were (45.10±6.08)×10-5,(48.20±1.21)×10-5,(22.10±3.18)×10-5,(59.10±1.21)×10-5 and (90.00±3.85)×10-5 s-1,respectively,and the effective permeability coefficient in duodenum,jejunum,ileum and colon was (44.10±0.51)×10-5,(17.21±0.77)×10-5,(35.36±0.31)×10-5 and (40.33±0.34)×10-5 cm/s,respectively.All in all, evodiamine lipidic nanoparticle remarkably improved the in situ intestinal absorption of evodiamine in different segments of the intestinal tract in rats and its oral bioavailability in rats.
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@#The stability and pharmacokinetic properties of hyaluronic acid-modified asparaginase (Asp) self-assembled bionic nanocapsules (ASNCs) were preliminarily investigated. ASNCs were prepared by molecular self-assembly method to investigate their morphology, particle size, zeta potential and antitrypsin stability. After intravenous injection of free Asp and ASNCs, rat plasma samples at different times were taken to determine Asp activity. Pharmacokinetic parameters were calculated by DAS pharmacokinetic software. The particle size of ASNCs was (99.17 ± 0.21) nm and the potential was -(13.13 ± 0.60) mV. In trypsin solution, ASNCs showed more excellent stability. The area under the activity-time curve (AUC0-48 h) of ASNCs was about 2 times higher than that of Asp; the mean residence time (MRT0-48 h) was about 1.7 times higher than that of Asp, and the bioavailability was 195% of Asp. The results showed that ASNCs could improve the stability and bioavailability of Asp against trypsin and prolong the circulation time of Asp in vivo.
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Although progress has been indeed made by nanomedicines, their efficacies for cancer treatment remain low, consequently leading to failures in translation to clinic. To improve the drug delivery efficiency, nanoparticles need to change size so as to fully utilize the enhanced permeability and retention (EPR) effect of solid tumor, which is the golden principle of nanoparticles used for cancer treatment. Herein, we employed cationic small-sized red emission bovine serum albumin (BSA) protected gold nanocluster (AuNC@CBSA, 21.06 nm) to both load indocyanine green (ICG) and act as imaging probe to realize theranostic. Then AuNC@CBSA-ICG was fabricated with negatively charged hyaluronic acid (HA) to form AuNC@CBSA-ICG@HA, which was about 200 nm to easily retain at tumor site and could be degraded by tumor-specific hyaluronidase into small nanoparticles for deep tumor penetration. The HA shell also endowed AuNC@CBSA-ICG@HA with actively targeting ability and hyaluronidase-dependent drug release. Furthermore, the quenching and recovery of fluorescence revealed the interaction between ICG and carrier, which was essential for the investigation of pharmacokinetic profiles. No matter or , AuNC@CBSA-ICG@HA showed markedly anti-tumor effect, and could suppress 95.0% of tumor growth on mice breast cancer model. All results demonstrated AuNC@CBSA-ICG@HA was potential for breast cancer therapy.
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Aim To observe the optimal temperature and optimal pH of uricase-catalase liposomes(UCALP) and free uricase(UAE), and study the abilities of UCALP to reduce uric acid and hydrogen peroxide in mice with hyperuricemia.Methods UCALP were prepared by reverse phase evaporation, optimal temperature and optimal pH of UCALP and UAE were determined, respectively.Mouse model of hyperuricemia was established by intraperitoneally injection of uric acid, and the model mice were intravenously injected UCALP and UAE, respectively, then the serum concentration of uric acid and hydrogen peroxide in mice at different time points were measured by the assay kits, respectively.Results Optimal temperature of UCALP and UAE was 40℃, and optimal pH was 8.0 and 8.5, respectively.UCALP could more significantly lower uric acid level of hyperuricemia mice than that of UAE, and the concentration of hydrogen peroxide in UCALP group was lower than in UAE group.Conclusion UCALP can effectively decrease the level of uric acid and control the level of hydrogen peroxide in mice with hyperuricemia.
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Aim To prepare the novel pyridostigmine bromide nanoemusion(PPNE)and study its release in vitro, and to investigate the intestinal absorption. Methods Pyridostigmine bromide (PB)and PPNE were tested by HPLC in pH 1 .2 HCl,pH 6.8,pH 7.4,pH 7.8 PBS.Rat single pass intestinal perfusion method was employed to investigate the absorption mechanism of PB and PPNE.Results PB release rate was faster than PB in the four release media;the intes-tinal absorption rate constant(Ka )and apparent perme-ability coefficient(Papp)of PPNE were increased in the duodenum,jejunum,ileum and colon segments.PB and PPNE had significant difference in the duodenum, jejunum,ileum and colon segments by t test (P <0.05).Conclusions PPNE can improve the bioavail-ability of drugs,increase the drugs permeability,sig-nificantly improve the absorption of the drugs in the in-testinal segments. PPNE has obviously sustained effects.
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OBJECTIVE:To establish a method for the simultaneous determination of acetic acid and succinic acid in Banxia syrup. METHODS:RP-HPLC was performed on the column of GL InterSustain-C18 with mobile phase of 0.03 mol/L ammonium di-hydrogen phosphate buffer solution(pH2.0)-methanol(gradient elution)at a flow rate of 0.8 ml/min,the detection wavelength was 210 nm,column temperature was 30 ℃,injection volume was 10 μl. RESULTS:The linear range was 0.020 98-0.209 8 μg/ml for acetic acid(0.999 9)and 12.04-120.4 μg/ml for succinic acid(r=0.999 9);limits of quantification were 0.15,18.24 ng,limits of detection were 0.045, 5.53 ng;RSDs of precision, stability and reproducibility tests were lower than 2%;recoveries were 97.45%-101.68%(RSD=1.39%,n=9) and 98.31%-101.08%(RSD=1.01%,n=9). CONCLUSIONS:The method is accurate and rapid,and suitable for the simultaneous determination of acetic acid and succinic acid in Banxia syrup.
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<p><b>OBJECTIVE</b>To study the pharmacokinetics and bioequivalence of asparaginase loaded in hyaluronic acid-graft-poly(ethylene glycol)/ sulfobutylether-β-cyclodextrin nanocapsules (AHSP) in SD rats.</p><p><b>METHODS</b>The morphology of AHSP was observed under the transmission electron microscope and the particle size and zeta potential were measured. AHSP and free asparaginase were intravenously injected in rats, and the plasma asparaginase activity was measured at different time points after the injections. The pharmacokinetic parameters were calculated using the software DAS 2.1.1 to assess the bioequivalence of AHSP and free asparaginase.</p><p><b>RESULTS</b>AHSP had an average particle size of 413.80∓10.97 nm with a zeta potential of -20.37∓2.38 mV. The AUC(0-48 h) of AHSP and free asparaginase was 137.34∓1.82 U/mL and 46.38 ∓1.98 U/mL, and their AUC(0-∞) was 164.66∓6.88 U/mL and 51.44∓3.01 U/mL with half-lives of 4.62∓0.60 h and 1.86∓0.38 h, respectively. Compared with free AN, AHSP exhibited increased AUC(0-48 h), AUC(0-∞), and half-life by 2.24, 2.55 and 2.32 folds, respectively. The 90% confidential intervals of AUC(0-48 h), AUC(0-∞) and Cmax of the tested formulation were 75.0%-76.5%, 74.3%-76.1%, and 95.1%-96.7%, respectively.</p><p><b>CONCLUSION</b>AHSP can improve the bioavailability and extend the biological half-life of asparaginase in rats, and AHSP and free asparaginase are not bioequivalent.</p>
Subject(s)
Animals , Rats , Area Under Curve , Asparaginase , Pharmacokinetics , Biological Availability , Half-Life , Injections, Intravenous , Nanocapsules , Rats, Sprague-Dawley , Therapeutic EquivalencyABSTRACT
<p><b>OBJECTIVE</b>To characterize the property of uricase loaded in uricase-catalase liposomes (BUCLPs) prepared using borate buffer.</p><p><b>METHODS</b>BUCLPs were prepared using reverse-phase evaporation, and the physicochemical properties of uricase in the prepared BUCLPs were examined.</p><p><b>RESULTS</b>The optimal temperature of BUCLP and URI was 40 degrees celsius, their optimal pH values were 8.0 and 8.5, and their Michaelis-Menten constants were 14.207 µmol/L and 13.623 µmol/L, respectively. Fluorescence intensity of nanoliposome-loaded uricase-catalase that bound to FITC was higher than that of uricase-catalase binding directly with FITC; the fluorescence intensity of BUCLP was higher than that of free uricase-catalase at 280 nm.</p><p><b>CONCLUSION</b>Uricase activity is enhanced after loading in uricase and catalase liposomes.</p>
Subject(s)
Borates , Catalase , Liposomes , Nanoparticles , Chemistry , Temperature , Urate Oxidase , ChemistryABSTRACT
Objective To establish a UPLC method for detecting content of imperatorin and isoimperatorin in huoxiang zhengqi oral liquid. Methods ACQUITY UPLC BEH C18 (2. 1 mmí50 mm,1. 7 μm) was used and the mobile phase was methanol and water by gradient elution mode. The column temperature was 30 ℃ ,the flow rate was 0. 3 mL·min-1 and the detection wavelength was 248 nm. Results The linear range of imperatorin was 1. 305-13. 050 μg·mL-1 and the regression equation was as follow Y =13 633X+3 976 (r=0. 999 9). The linear range of isoimperatorin was 0. 596-5. 960 μg·mL-1 and the regression equation was Y=10 661X+1 073 (r=0. 999 9). The average recovery was 99. 25% (RSD=0. 74% ) and 98. 94%(RSD = 0. 63% ),respectively. Conclusion The method is accurate, rapid and reliable, and can be used to determine imperatorin and isoimperatorin in huoxiang zhengqi oral liquid.
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<p><b>OBJECTIVE</b>To prepare curcumin-loaded poly-(D,L-lactide-co-glycolide) microspheres and study its release characteristics in vitro.</p><p><b>METHOD</b>Curcumin-loaded poly-(D,L-lactide-co-glycolide) microspheres were prepared by W/O/W emulsification solvent-evaporation process. The microspheres were characterized in terms of morphology, size, encapsulation efficiency, the rate of drug loading and in vitro drug release.</p><p><b>RESULT</b>The formed microspheres were spherical with smooth surfaces. The distribution of particle size was uniform and average size was 1 151 nm. The rate of drug loading was (1.98 +/- 0.14)% and the encapsulation efficiency was (59.44 +/- 4.05)%. In vitro release study revealed that the 71-hour accumulative release percentage reached 77%.</p><p><b>CONCLUSION</b>Curcumin loaded poly-(D,L-lactide-co-glycolide) microspheres are prepared successfully and show good sustained-release characteristics.</p>
Subject(s)
Biocompatible Materials , Chemistry , Curcumin , Chemistry , Drug Carriers , Chemistry , Microspheres , Particle Size , Polyglactin 910 , ChemistryABSTRACT
AIM To improve the treatmemt efficacy and reduce the side effect of carboplatin (CBP), the antitumor drug was incorporated into niosomes (NS). METHODS Lung targeted niosomes of CBP (CBP-NS) were prepared by the method of hand shaking. The ultraviolet absorption spectrophotometric method was used for the determination of CBP. The method of dynamic dialysis was used for in vitro release of CBP from CBP-NS. The S-180 lung neoplasms models were established by iv cancer cells in mice. The number of pulmonary nodules was examined for evaluating the therapeutic efficacy. RESULTS The data showed that the mean diameter of CBP-NS was 3.72 μm, with a span of 0.66. The entrapment ratio of CBP in CBP-NS was 29.2% and the CBP-NS were stable for three months stored at 3℃-5℃, 15℃-25℃ or 37℃ (relative humidity 75%). The release profile in vitro could be described by a biexpotential equation. The calculated values of the three targeting parameters indicated that CBP-NS showed good targeting efficiency. The results of therapeutic trials showed that the antitumor effects were significantly increased by injection of CBP-NS compared with CBP in the treatment of mice with lung carcinoma. CONCLUSION The results indicated that CBP-NS have good targeting efficiency in vivo, and the biodegradable CBP-NS may decrease the side effects of carboplatin and improve its therapeutic efficacy.
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OBJECTIVE:To observe the efficacy and safety of amifostine in prevention of nephrotoxicity induced by cisplatinum(DDP) METHODS:46 patients with malignant tumors were randomly divided into two groups:23 in chemotherapy and amifostine group(trial group)and 23 in single chemotherapy group(control group) Laboratory exmination indices such as blood routine,blood calcium,liver function,blood urea nitrogen,cretinine,and urinary ?1-microglobulin(?1-MG),albumin(Alb) and transferrin(TRF) were monitored at different time period points before and after treatment RESULTS:20 patients in each group completed the whole trial In the two periods of therapy,the peak values of ?1-MG,Alb and TRF of trial group were lower than those of control group(P