美迪紫檀素及其衍生物的植物来源及药理作用的研究进展

美迪紫檀素是一种紫檀类母核结构的黄酮类化合物,为鸡血藤的主要活性成分之一,具有抗肿瘤、促进骨生长、保护神经系统等药理作用,开发潜力较大。本文对美迪紫檀素及其衍生物的植物来源分布、药理作用、药物动力代谢学的研究进展进行综述,为促进美迪紫檀素的开发利用提供参考。

Pharmacokinetics of Scutellarin in Dogs

Aim To establish an RP-HPLC method for the determination of scutellarin in plasma and study its pharmacokinetics in dogs. Methods Scutellarin was given to dogs by intravenous injection and determined by RP-HPLC, the mean plasma concentration-time curve was plotted and pharmacokinetic parameters were calculated by program 3p87. Resu;ts The concentration-time curve of scutellarin could be fitted to three-compartment model with T1/2 pi, T1/2 α and T1/2 β being 1.05 ± 0.80 min, 6.99 + 2.76 min and 51.61 + 28.78 min, respectively, Vc being 880.1 + 508.3 mL, CL being 189.6 + 53.8 mL@ min- 1, and AUC0-90 and AUC0-∞ being 574.43 + 133.95 μg@ min@ mL - 1 and 599.34 ± 132.00μg@ min@mL- 1, respectively. Conclusion The fact that the concentrations of scutellarin in plasma declined rapidly after the medication suggested that the T1/2 of scutellarin should be taken into account in drug administration and preparation development.

Preparation and Pharmacokinetic Characterization of Sustained Release Melatonin Tablet

Aim To prepare the sustained release melatonin tablet with HPMC matrix and study its pharmacokinetics and bioavailatility. Methods HPMC was used as matrix to formulate the sustained release tablet. The influences of the size of melatonin, type and amount of HPMC, drug loading, type and amount of additives, and compressing pressure were investigated. Plasma concentration of melatonin in dogs after intravenous injection of two doses and oral administration of sustained release tablets and unmodified release capsules was detected by HPLC using fluorescence detector. Results The drug release from sustained release tablets was influenced by the size of melatonin, type and amount of HPMC, drug loading, and type and amount of additives. Melatonin was found to fit two compartment model after intravenous injection, AUC was proportional to doses, and t(1/2β) of two doses has no significant difference. Relative bioavailability of melatonin sustained release tablet to normal capsule was 83.8%, and absolute bioavailability was 3.75% for sustained release tablet and 4.49% for capsule. Conclusion The melatonin sustained release tablet was well formulated. The absolute bioavilability for oral administration of either sustained release tablet or unmodified release capsule of melatonin was less than 5%. The bioavailability of melatonin sustained release tablet was lower than that of unmodified release capsule, but MRT of sustained release tablet was significantly longer than that of capsule.

Determination of Sulphonylurea Glimepiride in Dog Serum by RP-HPLC with Pre-column Derivatization

Aim A simple, sensitive and rapid RP HPLC method with pre column derivatization has been developed for the determination of sulphonylurea glimepiride in dog serum. Methods The sulphonylurea glimepiride was extracted from the dog serum using dichlromethane followed by derivatization with DNBF for 20 min at 100℃. The solvent was then evaporated at 60℃ under nitrogen, and the residue was taken up in 100 μL of mobile phase consisting of acetonitrile water (75∶30, v/v). The separation was performed on a Hypersil BDS C18 column with a flow rate of 0 8 mL·min -1 , and the ultraviolet detector wavelength was set at 350 nm. Results Extraction recovery ranged from 75.9% to 83.2%, and methodological recovery was between 96.5% and 109.3%. Within day RSD ranged from 1.5% to 6.3%, and inter day RSD was between 2 9% and 14.8%. The method showed good linearity (R=0.9998). Conclusion The method was simple, convenient and sensitive. The reaction of derivatization was reproducible.

Pharmacokinetics of exendin-4 in Wistar rats

To characterize the preclinical pharmacokinetics, tissue distribution and excretion profiles of exendin-4 in healthy Wistar rats were studied. Exendin-4 was radioiodinated by the IODOGEN （1,3,4,6-tetrachloro-3 alpha, 6 alphadiphenylglucoluril） method. Pharrnacokinetic properties of ^125I-exendin-4 were examined after a single s.c. and i.v. injection, respectively. Tissue distri- bution and urinary, fecal, and biliary excretion patterns of ^125I-exendin-4 were also investigated following a single s.c. injection. Exendin-4 was rapidly distributed and cleared with t1/2 of （0.48 ± 0.03） h after a single i.v. injection. Following a single s.c. administration, exendin-4 exhibited rapid and considerable absorption with Tmax of （0.25± 0.02） h and declined with the elimination t1/2 of（1.28± 0.14） h. The absolute bioavailability was （65.5 ± 10.2） %. The radioactivity was widely distributed and rapidly diminished in most tissues. The kidney contained the highest radioactivity and the distribution of ^125I-exendin-4 to the brain was minimal. The major elimination route was urinary excretion. The pharmacokinetic properties of exendin-4 obtained from the present study closely matched those reported in previous studies in rats. Pharmacokinetics profiles of exendin-4 in rats are warranted for the design of future clinical trials.

Method for quantification of prazosin in dog plasma and its application to pharmacokinetic study

A simple and sensitive high performance liquid chromatography method using fluorescence detection （HPLC- FLD） and a one-step single solvent extraction for the determination of prazosin（PZS） in dog plasma is developed and validated. After extraction with ether, the chromatographic separation of PZS is carried out using a reverse phase C18 column （ 150 mm ×4.6 mm, 5 μm） with a mobile phase of 30% acetonitrile and 70% acetic acid-sodium acetate buffer solution （pH = 3.6） and quantified by fluorescence detection operated with an excitation wavelength of 258 nm and an emission wavelength of 387 nm. The flow rate of the mobile phase is 1.0 mL/min and the retention time of PZS and the internal standard is found to be 4. 4 and 5. 8 rain, respectively. The calibration curve is linear within a concentration range from 1.0 to 1 000.0 ng/mL （ P 〉 0. 998）. The limit of detection is 0.4 ng/mL. The inter-day coefficient of variation （COV） of the calibration standards is below 5.0% and the mean accuracy is in the range from 92. 7% to 104. 2%. Moreover, by analyzing quality control plasma samples for three days, the results show that the method is precise and accurate, for the intra- and inter- day COV within 10% and the accuracy from 95.9% to 112.7%. The developed and validated method is successfully applied to phannacokinetic study for the preclinical evaluation of a new peroral PZS-sulfobutyl ether beta-cyclodextrin （PZS-SBE-β-CD） inclusion complex tablets （test preparation）, which demonstrates that the test preparation released PZS is conducted in a slow and controlled way, and the relative bioavailability of the test preparation is found to be 105.0%.

Bayesian analysis for mixed-effects model defined by stochastic differential equations

The nonlinear mixed-effects model with stochastic differential equations （SDEs） is used to model the population pharmacokinetic （PPK） data that are extended from ordinary differential equations （ODEs） by adding a stochastic term to the state equation. Compared with the ODEs, the SDEs can model correlated residuals which are ubiquitous in actual pharmacokinetic problems. The Bayesian estimation is provided for nonlinear mixed-effects models based on stochastic differential equations. Combining the Gibbs and the Metropolis-Hastings algorithms, the population and individual parameter values are given through the parameter posterior predictive distributions. The analysis and simulation results show that the performance of the Bayesian estimation for mixed-effects SDEs model and analysis of population pharmacokinetic data is reliable. The results suggest that the proposed method is feasible for population pharmacokinetic data.

Pharmacokinetics of Recombinant E. coli L-asparaginase in Rats

The distribution of ^(125)I recombinant E. coli L-asparaginase in tissues ororgans and the excretion in urine, feces and bile were studied with in vivo radioactive tracertechnique. The amount of radioactivity excreted in urine, feces and bile within 24 h afterintravenous administration of ^(125)I recombinant E. col L-asparaginase to rats was 68.95% ,4.44%and 5.36% of the dose respectively. ^(125)I recombinant E. coli L-asparaginase in plasma samples wasdetermined. The levels of structural intact molecule in plasma samples were evaluated by SDS-PAGEand bio-imaging analyzer system. Pharmacokinetic parameters were assessed with a model-dependentmethod. The concentration-time curves of recombinant E. coli L-asparaginase after intravenousinjection at 1 250 IU·kg^(-1), 2 500, IU·kg^(-1), 5 000 IU·kg^(-1) to rats were consistent withthe two-compartment model. The first and terminal elimination t_(1/2) were 0.52 ~ 0.63 h and 2.39 ~2.76 h respectively. AUC was linearly related to the doses. The results of distribution in tissuesor organs and excretion in urine suggested that the metabolites of the enzyme were cleared bymechanisms of urinary excretion. Pharmacokinetics parameters of recombinant E. coli L- asparaginasein rats are warranted for the design of future clinical trials.

Mechanistic considerations for the use of monoclonal antibodies for cancer therapy

Since the approval of rituximab in 1997, monoclonal antibodies(mAbs) have become an increasingly important component of therapeutic regimens in oncology. The success of mAbs as a therapeutic class is a result of great strides that have been made in molecular biology and in biotechnology over the past several decades. Currently, there are 14 approved mAb products for oncology indications, and there are ten additional mAbs in late stages of clinical trials. Compared to traditional chemotherapeutic agents, mAbs have several advantages, including a long circulating half-life and high target specificity. Antibodies can serve as cytotoxic agents when administered alone, exerting a pharmacologic effect through several mechanisms involving the antigen binding(Fab) and/or Fc domains of the molecule, and mAbs may also be utilized as drug carriers, targeting a toxic payload to cancer cells. The extremely high affinity of mAbs for their targets, which is desirable with respect to pharmacodynamics(i.e., contributing to the high therapeutic selectivity of mAb), often leads to complex, non-linear, target-mediated pharmacokinetics. In this report, we summarize the pharmacokinetic and pharmacodynamics of mAbs that have been approved and of mAbs that are nearing approval for oncology indications, with particular focus on the molecular and cellular mechanisms responsible for their disposition and efficacy.

Rational prescription of drugs within similar therapeutic or structural class for gastrointestinal disease treatment: Drug metabolism and its related interactions

AIM:To review and summarize drug metabolism and its related interactions in prescribing drugs within the similar therapeutic or structural class for gastrointestinal disease treatment so as to promote rational use of medicines in clinical practice.METHODS:Relevant literature was identified by performing MEDLINE/Pubmed searches covering the period from 1988 to 2006.RESULTS:Seven classes of drugs were chosen,including gastric proton pump inhibitors,histamine H2-receptor antagonists,benzamide-type gastroprokinetic agents,selective 5-HT3 receptor antagonists,fluoroquinolones,macrolide antibiotics and azole antifungals.They showed significant differences in metabolic profile(i.e.,the fraction of drug metabolized by cytochrome P450(CYP),CYP reaction phenotype,impact of CYP genotype on interindividual pharmacokinetics variability and CYP-mediated drug-drug interaction potential).Many events of severe adverse drug reactions and treatment failures were closely related to the ignorance of the above issues.CONCLUSION:Clinicians should acquaint themselves with what kind of drug has less interpatient variability in clearance and whether to perform CYP genotyping prior to initiation of therapy.The relevant CYP knowledgehelps clinicians to enhance the management of patients with gastrointestinal disease who may require treatment with polytherapeutic regimens.

Pharmacokinetics and bioequivalence of ranitidine and bismuth derived from two compound preparations

AIM： To evaluate the bioequivalence of ranitidine and bismuth derived from two compound preparations. METHODS： The bioavailability was measured in 20 healthy male Chinese volunteers following a single oral dose （equivalent to 200 mg of ranitidine and 220 mg of bismuth） of the test or reference products in the fasting state. Then blood samples were collected for 24 h. Plasma concentrations of ranitidine and bismuth were analyzed by high-performance liquid chromatography and inductively coupled plasma-mass spectrometry （ICPMS）, respectively. The non-compartmental method was used for pharmacokinetic analysis. Log-transformed Cmax, AUC（0-t） and AUC（0-∞） were tested for bioequivalence using ANOVA and Schuirmann two-one sided t-test. Tmax was analyzed by Wilcoxon＇s test. RESULTS： Various pharmacokinetic parameters of ranitidine derived from the two compound preparations, including Cmax, AUC（0-t）, AUC（0-∞）, Tmax and T1/2, were nearly consistent with previous observations. These parameters derived from test and reference drug were as follows： Cmax（0.67 ± 0.21 vs 0.68 ± 0.22 mg/L）, AUC（0-t）（3.1 ± 0.6 vs 3.0 ± 0.7 mg/L per hour）, AUC（0-∞）（3.3 ± 0.6 vs 3.2 ± 0.8 mg/L per hour）, Tmax （2.3 ± 0.9 VS 2.1 ± 0.9 h） and T1/2 （2.8 ± 0.3 vs 3.1 ± 0.4 h）. In addition, double-peak absorption profiles of ranitidine were found in some Chinese volunteers. For bismuth, those parameters derived from test and reference drug were as follows： Cmax （11.80 ± 7.36 vs 11.40 ± 6.55 μg/L）, AUC（0-t） （46.65 ± 16.97 vs 47.03 ± 21.49 μg/L per hour）, Tmax （0.50 ± 0.20 vs 0.50 ± 0.20 h） and T1/2 （10.2 ± 2.3 vs 13.0 ± 6.9 h）. Ninety percent of confidence intervals for the test/reference ratio of Cmax, AUC（0-t） and AUC（0-∞） derived from both ranitidine and bismuth were found within the bioequivalence acceptable range of 80%-125%. No significant difference was found in Tmax derived from both ranitidine and bismuth. CONCLUSION： The two compound preparations are bioequivalent and may be prescribed interchangeably.

Impact of release characteristics of sinomenine hydrochloride dosage forms on its pharmacokinetics in beagle dogs

AIM： To investigate the effect of release behavior of sustained-release dosage forms of sinomenine hydrochloride （SM·HCl） on its pharmacokinetics in beagle dogs. METHODS： The in vitro release behavior of two SM·HCl dosage forms, including commercial 12-h sustained-release tablets and 24-h sustained-release pellets prepared in our laboratory, was examined. The two dosage forms were orally administrated to beagle dogs, and then the in vivo SM.HCI pharmacokinetics was investigated and compared. RESULTS： The optimal SM·HCl sustained-release formulation was achieved by mixing slow- and rapidrelease pellets （9：1, w/w）. The SM·HCl release profiles of the sustained-release pellets were scarcely influenced by the pH of the dissolution medium. Release from the 12-h sustained-release tablets was markedly quicker than that from the 24-h sustained-release pellets, the cumulative release up to 12-h was 99.9% vs68.7%. From a pharmacokinetic standpoint, the 24-h SM.HCI sustainedrelease pellets had longer tmax and lower Cmax compared to the 12-h sustained-release tablets, the tmax being 2.67±0.52 h vs 9.83±0.98 h and the Cmax being 1334.45±368.76 ng/mL vs 893.12±292.55 ng/mL, respectively. However, the AUC0-tn of two SM·HCl dosage forms was comparable and both preparations were statistically bioequivalent. Furthermore, the two preparations had good correlations between SM·HCl percentage absorption in vivoand the cumulative percentage release in vitro. CONCLUSION： The in vitro release properties of the dosage forms strongly affect their pharmacokinetic behavior in vivo. Therefore, managing the in vitro release behavior of dosage forms is a promising strategy for obtaining the optimal in vivo pharmacokinetic characteristics and safe therapeutic drug concentration-time curves.

Pharmacokinetic study with N-Ile^1-Thr^2-63-desulfato-r-hirudin in rabbits by means of bioassay

Aim： To study the pharmacokinetic （PK） properties in rabbits treated with N-Ile^1-Thr^2-63-desulfato-r-hirudin （rH） newly developed in China by means of bioassay in order to provide preclinical experiment basis for its development as a novel anticoagulant agent. Methods： rH plasma concentration was determined using bioassay based on ex vivo antithrombin activity of rH. Normal rabbits received iv rH 4.0, 2.0 and 1.0 mg/kg or sc rH 2.0 mg/kg, respectively. The rabbits with acute severe renal failure were given iv rH 2.0 mg/kg. Results： The bioassay described in this paper met requirements for study of PK in rabbits. The major PK parameters after iv dosing were as follows： t1/2p 58.4-59 min. Vd 0.09-0.12 L/kg, CL 0.0035-0.0040 L/（kg·min）; AUC were proportional to the doses, ti/2 and CL did not change significantly with the doses. The sc bioavailability reached 94%. The rabbits suffering from acute severe renal failure presented 11-fold longer t1/2p and 13-fold greater.4 UC than normal healthy rabbits. Conclusion： rH exhibited rapid elimination, distribution was only limited to extracellular space and good absorption from sc site. The excretion ofrH by kidneys played a very important role in the elimination of rH. The PK ofrH could be described by the two- and one-compartment model after iv and sc dosing, respectively, and folio,wed linear kinetics.

Pharmacokinetics and Bioavailability of 2-Amino-6-Cyclopropylamino-9-(2,3 -Dideoxy-β-D-glyceropent-2-enofuranosyl) Purine (Cyclo-D4G) in Rats

AimTo characterize the pharmacokinetics of 2 -amino-6-cyclopropylamino-9-(2,3-dideoxy-β-D-glyceropent-2-enofuran osyl) purine (Cyclo-D4G) following intravenous administration and oral administ ration to rats. MethodsThe concentrations of Cyclo-D4G in rat (Sprague-Dawley male rats) plasma and urine were analyzed by high performance liquid chromatography (HPLC). ResultsFollowing intravenous adm inistration to rats, concentrations of Cyclo-D4G in plasma declined with a term inal phase half-life of 0 78±0 14 h (±s). Total clearance was 0 90±0 21 L·h -1 ·kg -1 . Renal excretion of unchanged Cyclo-D4G accounted for approximately 20% of total clearance. Steady state volume of distr ibution was 0 91±0 07 L·kg -1 . After oral administration to rats, conce ntrations of Cyclo-D4G in plasma declined with a terminal phase half-life of 0 83±0 13 h (±s). Total clearance was 3 81±2 03 L·h -1 ·kg -1 . Renal excretion of unchanged Cyclo-D4G accounted for approximat ely 9% of total clearance. Oral bioavailability of Cyclo-D4G in rat was 26 9%. ConclusionThe favorable pharmacokinetic profiles and lower to xicity provide support for further development of Cyclo-D4G clinical trials.

Pharmacokinetics and Pharmacodynamics of Subcutaneous Single Doses of Pegylated Human G-CSF Mutant(PEG30-rhG-CSF) in Beagle Dogs

OBJECTIVE To compare the pharmacokinetics and pharmacodynamics of PEG30-rhG-CSF administered to beagle dogs at three different dosages with PEG20-rhG-CSF administered at one dosage, and to provide an experimental basis for clinical trials.METHODS Beagle dogs received single, subcutaneous doses of PEG30-rhG-CSF at 100, 200 and 400 μg/kg or PEG20-rhG-CSF at 200 μg/kg. PEG30-rhG-CSF and PEG20-rhG-CSF concentrations in serum were analyzed using an enzymeqinked immunosorbent assay （ELISA）. WBC, ANC and PLT counts of whole blood samples were measured using fully automated analytic instrumentation. Pharmacokinetic and pharmacodynamic parameters were calculated using DAS 2.0 statistical analysis software.METHODS Beagle dogs received single, subcutaneous doses of PEG30-rhG-CSF at 100, 200 and 400 μg/kg or PEG20-rhG-CSF at 200μg/kg. PEG30-rhG-CSF and PEG20-rhG-CSF concentrations in serum were analyzed using an enzyme-linked immunosorbent assay （ELISA）. WBC, ANC and PLT counts of whole blood samples were measured using fully automated analytic instrumentation. Pharmacokinetic and pharmacodynamic parameters were calculated using DAS 2.0 statistical analysis software. RESULTS The pharmacokinetic parameters of PEG30-rhG-CSF calculated from the serum concentration data determined by ELISA were as follows： the mean elimination half-life （t1/2ke） was 40.6 h （33.5-45.4 h）; the mean time to reach peak concentration （Tmax） was 19.2 h （11.7-24.0 h）; the drug clearance from the serum （CL） was decreased with increasing doses; the peak concentration （Cmax） and the area under the serum concentration-time curve （AUC） were increased with increasing doses. For PEG20-rhG- CSF, the half-life was shorter （12 h） and Tmax was achieved much earlier （10 h） relative to PEG30-rhG-CSF. The AUC of PEG30- rhG-CSF was much greater than that of PEG20-rhG-CSF, and the relative bioavailability with a subcutaneous injection was 158.7%. Administration of single doses of PEG30-rhG-CSF resulted in substantial increases in the absolute The time to reach ANC （ANCTmax） neutrophil count （ANC）. was 72 h. The maximum observed absolute neutrophil counts （ANCmax） and the area over the baseline effect curve （AOBEC） was increased with increasing doses. The effect-elimination half-life （t1/2E） ranged from 60 h to 80 h after subcutaneous administration. The PLT count was slightly elevated 8-12 h after s.c. injection, and declined after 24 h. CONCLUSION The mean elimination half-life of PEG30-rhG- CSF was longer than that of PEG20-rhG-CSF at the same dose, and the other main pharmacokinetic and pharmacodynamic parameters of PEG30-rhG-CSF, including C ANCmax, AUC and AOBEC were much greater than those following PEG20-rhG-CSF injection.

Pharmacokinetics of paclitaxel in a hemodialysis patient with advanced gastric cancer: A case report

We report for the first time the possibility of weekly paclitaxel chemotherapy for a patient with advanced, nonresectable gastric cancer undergoing hemodialysis. A 50-year-old man with chronic renal failure due to bilateral polycystic kidneys, who had undergone hemodialysis three times a week for 5 years, presented with hematemesis in December 2004. Based on the diagnosis of gastric cancer with lymph node metastases, surgery was performed. On the 15th postoperative day, the patient was treated with chemotherapy using paclitaxel. Paclitaxel was administered at a dose of 60 mg/m^2 as a 1 h iv infusion in 250 mL of saline. Hemodialysis was started 1 h after the completion of the paclitaxel infusion and was performed for 3 h. Paclitaxel was administered weekly on d 1, 8, and 15 on a 28-d cycle. The maximum plasma concentration of paclitaxel was 1390 μg/L. The area under the curve of paclitaxel was 4398.6 μg·h/L. Grade 2 leukopenia was encountered during the first cycle. The plasma concentrations of paclitaxel from 6 to over 24 h after the infusion were 0.01 to 0.1 μmol/L in our patient, and these concentrations have been shown to be effective on inhibiting the growth of gastric cancer cells without producing adverse side effects in the patient. The plasma concentration of paclitaxel was not influenced by hemodialysis. We conclude that the pharmacokinetics of paclitaxel is not altered in a patient with renal failure, and that weekly paclitaxel is a suitable treatment regimen for hemodialysis patients with advanced gastric cancer.

Determination of 2-Amino-6-Cyclopropylamino-9-(2,3-Dideoxy-β-D-glyceropent-2-enofuranosyl)purine in Rat Plasma,Urine and Liver Homogenates by High Performance Liquid Chromatography

Aim To develop a simple and specific high-performance liquid chromatographic(HPLC) method, suitable for the pharmacokinetic studies in vivo, to determine the concentrations of2-amino-6-cyclopropylamino-9-(2,3-dideoxy-β-D-glyceropent-2-enofuranosyl)purine (Cyclo-D4G, IMGprodrug) in rat plasma, urine and liver homogenates. Methods Chromatography was performed with C-18Hypersil ODS column and a mobile phase of 7% (v/v) acetonitrile in phosphate buffer, pH 7.40, withUV detection at 283 nm. Results The average extraction recovery of Cyclo-D4G in rat plasma and urinewas 100.1% over its linear range of 0.5 - 80 μg·mL^(-1). The accuracy of the assay was 99.4% .The intra-and inter-day RSDs were less than 9.0% . Conclusion The analytical method was found to beapplicable, reliable and suitable for pharmacokinetic studies.

PHARMACOKINETICS OF PARACETAMOL ORALLY DISINTEGRATING AND GENERAL TABLETS IN HEALTHY VOLUNTEERS

Objective To compare the pharmacokinetics and relative biological availability of Paracetatool orally disintegrating tablets and general tablets in healthy volunteers. Methods In a random two periods crossover study, 19 healthy male Chinses volunteers received a single dose of Paracetamol 500mg of two formularies respectively. The plasma concentration of paracetamol was determined by HPLC method. The pharmacokinetic parameters of the two preparation and the relative biological availability of Paracetamol orally disintegrating tablets and general tablets were caculated with statistical analysis. Results The main pharmacokinetic parameters of paracetamol orally disintegrating tablets and general tablets were （ 31436. 70 ± 7062. 80 μg · h^ -1· L^-1 and （29871.40 ± 7965.04） μg · h^ -1· L^-1 for AUC0-1 （33295. 7 ±7663. 10） μg · h^ -1· L^-1 and（31845. 20 ± 8830. 83 ） μg · h^ -1· L^-1 forAUC0-1（9. 71 ±2. 78） μg/ml and（10. 36 ±3. 86） μg/mlfor Cmax; （0. 82 ±0. 45）h and （0. 74± 0.67）hforTmax;（2.90±0. 42）h and （3. 13 ±0. 67）h for T1/2ke;（0.24 ±0.04） and （0.23 ±0.04） for Ke; （4. 1481±0. 4492 ） and （4. 0771 ±0. 8131 ） for mean residence time （ MRT） , respectively. Variance analysis showed that there was significant difference in AUC0-12 and Cmax between the two preparations. Conclusion The paracetamol orally disintegrating tablets and general tablets are bioequivalent and the relative biological availability of Paracetamol orally disintegrating tablets is （ 108 ± 19） %.

PHARMACOKINETICS OF MAGNESIUM ISOGLYCYRRHI-ZINATE AFTER SINGLE INTRAVENOUS DOSE IN HEALTHY VOLUNTEERS

Objective To study the pharmacokinetics of intravenous magnesium isoglycyrrhizinate injection in health volunteers with HPLC-UV. Methods Single doses of 2OOmg magnesium isoglycyrrhizinate were administrated to 10 health volunteers by i. v. infusion. The concentrations of magnesium isoglycyrrhizinate in plasma were assayed by HPLC-UV method. The pharmacokinetic parameters of magnesium isoglycyrrhizinate injection were calculated by program 3P87. Results The main pharmacokinetic parameters of intravenous magnesium isoglycyrrhizinate were as follows： cmax （ 67. 58 ± 8. 84 ） mg/L, T1/2α （ 1.46 ± 0. 35 ） h, T1/2β （ 23. 95 ± 4. 72 ） h, Vd （ 2. 921 ± 0. 382） L, CL （0. 186 ±0. 048） L/h,k10（0. 064 ±0. 016） h^-1, AUC0-T（1015.29 ±225. 14） mg·h^-1·L^-1 ,respectively. Conclusion We have successfully used the analytical method for magnesium isoglycyrrhizinate to study its pharmacokinetical properties of health volunteers after i. v. infusion. The method is found to be simple, accurate, stable and sensitive for application in clinical pharmacokinetics study. The concentration-time plot was fitted to a two-compartment open model with first-order elimination.

Simultaneous determination of sunitinib and its active metabolites N-desethylsunitinib(SU12662) in nude mice plasma by liquid chromatography tandem mass spectrometry and its application to a pharmacokinetic study

A sensitive, rapid, and simple liquid chromatography tandem mass spectrometry（LC-MS/MS） method for simultaneous determination of sunitinib and its active metabolites in plasma of BABL/c nude mice was developed and validated. Plasma samples were pre-treated by protein precipitation with pazopanib and used as an internal standard. Separation was performed on a reversed phase C18 column with a mobile phase composing of 10 m M ammonium formate p H 3.25（adjusted with formic acid） and acetonitrile（65：35, v/v） at a flow rate of 0.5 mL /min. Triple quadrupole tandem mass in multiple reaction monitoring（MRM） mode with electrospray positive ionization was used to monitor all the compounds. The current LC-MS/MS method was highly selective and sensitive with lowest limit of quantitation（LLOQ） of 0.5 ng/mL for both analytes and reliable intra- and inter-day precision and accuracy validated by relative error（RE%） and relative standard deviation（RSD%）. Linearity of calibration curve was excellent（r0.99） within a concentration range of 0.5–1000 ng/mL. This method was successfully applied to a pharmacokinetics study on BABL/c nude mice given with single dose of oral administration of sunitinib at 20 mg/kg.