AIM: To study the absorption and distribution characteristics of oxybutynin (OXY) oral tablet and transdermal gel. METHODS: A single dose of 0.1 g OXY transdermal gel (2 mg OXY) was applied to abdominal area about 4 cm2 and 0.5 mg immediate-release tablet was orally given to 48 rats in a randomized, open-label, control design test. The plasma, bladder and liver tissue were collected, disposed and analyzed and OXY pharmacokinetic parameters were calculated and evaluated. RESULTS: The Cmax of OXY transdermal gel and oral tablets in bladder are approximately 800 and 70 times higher than those in plasma. The plasma half life of OXY gel delayed 5.99 h, tablets 2.18 h. CONCLUSION: OXY gel show better pharmacokinetic properties, characterized with long half life and high target organ concentrations than those of tablets.

Aim To evaluate the bioequivalence of demestic brodimoprim capsules and imported hyprim tablets and provide experimental basis for clinical application. MethodsA single dosage of Brodimoprim or hyprim was given to 18 healthy volunteers in a randomized 2-way cross-over test and the brodimoprim concentrations in plasma were determined by HPLC with β-naphtol as internal standard. The pharmacokinetic parameters and the relative bioavailability of the two preparations were calculated and their bioequivalence was evaluated. ResultsThe major pharmacokinetic parameters of test and reference preparations were as follows respectively:t1/2(α) (2.1 + 1.0) and (1.9+± 0.9) h, t1/3(β)(43.2±4.8) and (42.4±4.3)h, Tpeak(3.4±1.6) and (3.1±1.5) h,Cmax(5.9+ 0.9) and (5.9±1.0)μg · ml-1, AUC0～132(360.2± 55.3) and (358.7±52.6) μg · h · ml-1, AUC0～∞ (423.8±56.0) and (422.5±51.1) μg · h · ml-1. The relative bioavailability(F) of brodimprim capsules was (99.7± 4.8)%。 Conclusion . The multi-factorial analysis of variance showed that there was no significant difference in AUC0- 132between the test and reference preparations (P＞ 0.05) . The bioequivalent assumption was proved by further two one-side t-test and (1～2 α) confidence interval analysis in individuals, periods and forms of these two preparations.

OBJECTIVE:To compare benproperine sustained-release tablet(BP)with cofrel tablet(CF)in respect to the bioequivalence,release characteristics and correlation between in vitro dissolubility and in vivo absorption METHODS:A HPLC method was used to determine the serum benproperine concentration after single and multiple oral administration of 80mg BP and CF in a two-period cross-over test RESULTS:The T1/2(?),Tpeak,Cmax,AUC0～36,AUC0～∞ of BP after single and multiple oral administration were (11 99?1 15)h and (11 91?1 41)h,(3 80?0 42)h and (2 25?0 26)h,(0 2 787?0 03)?g/ml and (0 4 507?0 07)?g/ml,(4 1 445?0 48)?g/(ml?h)and (3 8 981?0 54)?g/(ml?h),(4 7 908?0 42)?g/(ml?h) and (4 3 278?0 55)?g/(ml?h),and those of CF were (11 68?1 24)h and (10 83?1 01)h,(3 10?0 26)h and (1 95?0 16)h,(0 4 737?0 32)?g/ml and (0 6 163?0 42)?g/ml,(9 3 954?0 80)?g/(ml?h) and (8 5 223?0 76)?g/(ml?h),(10 1 336?0 87)?g/(ml?h) and (8 8 821?0 77)?g/(ml?h),respectively The relative bioavailability of BP versus CF was(112 40?0 06)% CONCLUSION:The results show that the benproperine sustained-release tablet and cofrel are bioequivalent

AIM: To determine the concentration of nisoldipine in human plasma by HPLC-MS method and investigate the pharmacokinetics of sustained and immediate-release preparations. METHODS: A C 18 column was used to separate nisoldipine from plasma with the mobile phase of a mixture of methanol-water-acetic acid (7525 0.1) at a flow rate of 1.0 ml?min -1. MS: atmospheric pressure electronic spray ionization (AP-ESI) and ion mass spectral (m/z) of 411 were selected to quantify nisoldipine. Internal standard (IS): atmospheric pressure electronic spray ionization and m/z of 441 for nimodipine. RESULTS: The linear range of the standard curve of nisoldipine was 0.2- 50 ?g?L -1 and the determination limit was 0.15 ?g?L -1. The recovery rate was more than 70%, and intra-day relative standard deviation (RSD) and inter-day RSD were less than 10%. After being given a single dose of 10 mg nisoldipine sustained release tablet, sustained release capsule and normal tablet, the half life(t 1/2 /h) were 6.08? 1.48, 7.06? 1.80 and 3.70? 0.25, the time to peak concentration (T peak /h) were 5.4? 0.7, 5.8? 0.4 and 2.0? 0.2, the peak concentration (C max / ?g?L -1) were 3.43? 0.55, 3.71? 0.24 and 9.18? 3.78, the area under time- concentration curve (AUC 0-t / ?g?h -1?L -1) were 31.10? 5.00, 33.63? 7.16 and 32.72? 5.09. But after being given multiple doses of nisoldipine, C max/ ?g?L -1 were 5.20? 0.27, 3.91? 0.22 and 5.30? 1.04, C min / ?g?L -1 were 0.72? 0.10, 0.77? 0.07 and 0.53? 0.07, DF were 175.00%? 16.34%, 177.10%? 18.43% and 247.92%? 57.71% respectively. The bioavailability of sustained- release tablet and capsule were 96%?12% and 102%?9% respectively. CONCLUSION: The determination of concentration of nisoldipine in human plasma by HPLC-MS method is sensitive and accurate. It can be used for the investigation of the bioavailability and pharmacokinetic of nisoldipine.

AIM: To establish a sensitive HPLC method for determining the concentrations of paeonol in human plasma and to evaluate its pharmacokinetic characteristics. METHODS: A single oral dose of 160 mg paeonol capsules was given to 24 Chinese healthy volunteers. Paeonol was separated on a XB-C18 column with tetrahydrofuran-methanol-water-phosphonic acid (6∶60∶34∶0.1, V∶V) as mobile phase. The plasma concentrations of paeonol were determined and its pharmacokinetic parameters were calculated and evaluated using DAS 2.0. RESULTS: The linear range of the paeonol was 10-500 ng/mL and the determination limit was 10 ng/mL. The main pharmacokinetic parameters, as Cmax, tmax, t1/2,AUC0-3, AUC0-∞ after a single dose of paeonol capsules were (116±46)ng/mL,(1.02±0.13) h,(1.03±0.35) h, (174±45) ng/mL, (217±56) ng/mL,respectively. CONCLUSION: The HPLC method for determining paeonol concentration in plasma is rapid, sensitive and suitable for pharmacokinetic studies.

AIM:To establish an LC-MS method for determining the concentrations of loratadine (LOR) in human plasma and to evaluate its pharmacokinetic characteristics. METHODS: A ZORBAX Eclipse XDB-C8 (5 μm, 150 mm×4.6 mm) column was used, atmospheric pressure electronic spray ionization (AP-ESI) and ion mass spectrum (m/z) of 388.2 (M+H)+ were selected to quantify LOR, and 275.1 (M+H)+ for ropivacaine (internal standard, IS). RESULTS: The linear range of LOR standard curve was 0.5-50 ng·ml-1, and the determination limit was 0.5 ng·ml-1. The pharmacokinetic parameters of LOR after a single dose of 20 mg tablet (T1), capsule (T2) and reference (R) were as follows, the half life (t1/2) 13.52±1.35, 13.14±0.98 and 14.00±1.25 h, the time to peak concentration (Tmax) 1.24±0.06, 1.18±0.12 and 1.17±0.12 h, the peak concentration (Cmax) 21.72±7.70, 21.49±8.34 and 20.50±8.65 ng·ml-1, the area under time-concentration curve (AUC0-48 and AUC0-∞) 137.24±47.84 and 146.61±51.03 ng·ml-1·h, 139.65±45.69 and 148.04±48.10 ng·ml-1·h, 134.19±49.03 and 143.70±52.08 ng·ml-1·h, the relative bioavailability of LOR tablet and capsule were (105.49±8.08)% and (102.90±10.02)%, respectively. CONCLUSION: The LC-MS method for determining the concentration of LOR in human plasma is sensitive and accurate and can be used for LOR bioavailability and pharmacokinetic studies. LOR tests and reference are bioequivalent.

Objective:To explore the abortion effect and mechanism induced by Chinese herbal medicine rhubarb extract.Methods:The pregnant mice at day 3 of gestation were Drenched by Aqueous extract of rhubarb at different doses (7,5,2.5 g/kg)once per day for five days,and mices in control group were oral administration of same volume of saline.All mices at 12 day of gestation were sacrificed.estradiol and progesterone levels in serum were detected by Radioimmunoassay;Content of IFN-γ, IL-2 and TNF-αin uterine lysates were measured by ELISA, macrophages in endometrium were determined by immunohistochemical method, mast cells in endometrium were tested by Toluidine blue staining, respectively.Results: showed as follows:With increasing dose of rhubarb extract,abortion rate and resorption rate were gradually increased and was 100%abortion in 7g/kg treatment groups.Estrogen and progesterone content showed a downward trend,IFN-γ,IL-2 and TNF-αin uterine lysates and the numbers of macrophages and mast cells were significantly higher in mices Drenched by Aqueous extract of rhubarb than in the control.Conclusion: These results show that rhubarb extract not only interfere stability of pregnancy state in pregnant mices because of its diarrhea,but also can directly affect endometrial environment in early embryonic mice,Resulting in abortion.

OBJECTIVE:To develop a method for the determination of paraquat in human plasma,and to provide experimen-tal evidence for the therapy and prognosis of paraquat-poisoned patients. METHODS:The human plasma samples were processed using Waters Oasis solid phase extraction column. HPLC determination was performed on DiamonsilTM C18 chromatographic column with mobile phase consisted of 0.1 mol/L phosphate buffer(containing 80 mmol/L sodium heptanesulfonate,pH adjusted to 3.0 by triethylamine)-acetonitrile (82∶18,V/V) at the flow rate of 0.9 ml/min. The detection wavelength was set at 258 nm. RESULTS:The linear range of paraquat were 20-5 000 ng/ ml;RSDs of inter-day and intra-day both were lower than 9%;average extraction recoveries were 90.72%-96.34%,and average method recoveries were 100.32%-103.10%. CONCLUSIONS:The solid phase ex-traction HPLC can determine the content of paraquat in human plasma rapidly and accurately.

AIM: To establish a simple, rapid and accurate high performance liquid chromatographic method (HPLC) for the determination of cyclosporin A (CsA) in human whole blood, and to study the influence of nicotinylmethylamide (Nic) on the pharmacokinetic parameters of cyclosporin A (CsA). METHODS: Whole blood CsA concentrations were measured by HPLC in 18 healthy volunteers administrated single CsA or co administrated Nic. The data of time blood concentrations of CsA were analyzed by 3p97 Program. The analysis of variance and two one sided t test were used to compare the main pharmacokinetic parameters of CsA in the two administrations. RESULTS: C max and AUC 0～∞ of CsA had statistically significance between the single CsA group and co administration of Nic group (P0.05). CONCLUSION: This HPLC method is simple, sensitive and accurate, and is suitable for routine determination of blood CsA levels in human. Nic can improve the absorption of CsA and increase the C max and AUC of CsA, but has no influence on the metabolism of CsA.