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Objective:To optimize the clinical dosage regimen of amoxicillin and clavulanate potassium extended release ( ER) tablets based on the PK/PD parameters. Methods:Totally 30 healthy subjects ( half male and half female) were randomly divided into three groups, and orally administered the ER tablets respectively under fasting condition, before the meal and after the meal, and the optimal administration time was determined by comparing the pharmacokinetic characteristics. The subjects in the three groups were ad-ministered the ER tablets respectively at low, medium and high dosage, and the optimal dosage and dosing interval were determined based on the PK/PD parameters. Results:Under fasting condition, the AUC of amoxicillin [(32.2 ±15.0) μg·h·ml-1] was sig-nificantly lower than that before the meal [(41.7 ±1.92) μg·h·ml-1] and that after the meal [(42.6 ±17.7) μg·h·ml-1]. In contrast, the AUC of clavulanate acid after the meal [(1.89 ±0.54) μg·h·ml-1] was significantly lower than that under fasting condition [(2.55 ±0.76) μg·h·ml-1] and that before the meal [(2.58 ±0.76) μg·h·ml-1] (P MIC) in 12 h was 5. 5, 7 and 10 h, and the percentage was 46%, 58% and 83%, respectively, and T> MIC in 12 h was 4. 5, 6 and 8 h, and the percentage was 38%, 50% and 67%, re-spectively when MIC was 4. 0μg·ml-1 . Conclusion:It is suggested that amoxicillin and clavulanate potassium ER tablets be taken at the start of a standard meal, 2 tablets per time, twice daily, which is sufficient to achieve T> MIC of 40% -50%.
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Objective To establish an analytical method for assessing acetylcysteine in human plasma and study the relative bioavailability and bioequivalence of acetylcysteine granules in Chinese healthy volunteers. Methods In the randomized crossover study, 24 healthy male volunteers received a single oral dose of 0. 6 g test acetylcysteine granules, reference acetylcysteine granules or no medication. The plasma concentration of acetylcysteine was determined by LC-MS/MS. Pharmacokinetic parameters were calculated and bioequivalence of two preparations were evaluated by DAS3. 0 software. Results The main pharmacokinetic parameters of the test and reference preparations were as follows:AUC0→t was (8 547. 64± 2 860.04) and (8 783.07±4 042. 10) μg·h·L-1, respectively; AUC0→∞ was (9 481. 64±3 444. 76) and (9 540. 51± 4 239. 30) μg·h·L-1, respectively;Cmax was (1 994. 39±726. 42) and (2 090. 27±885. 46) μg·L-1, respectively;tmax was (1.18±0. 60) and (1. 13±0. 53) h, respectively; t1/2 was (8. 60±3. 76) and (7. 75±5. 01) h, respectively. The relative bioavailability F0→t and F0→∞ was ( 107. 0 ± 43. 3 )% and ( 106. 5 ± 40. 1 )%, respectively. Conclusion The results of statistical analysis indicate that the test and reference formulations are bioequivalent.
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Objective: To evaluate the bioavallability and bioequivalence of rabeprazole sodium enteric-coated pellets capsules. Methods:A randomized crossover design was performed in 32 healthy male volunteers. A single oral dose of 20 mg rabeprazole sodium enteric-coated pellets capsules ( test preparation) or enteric-coated shell capsules ( the reference capsules) was administrated under fed conditions. The wash period was 7 days. The blood samples were collected at different time points. The concentration of rabeprazole in plasma was determined by an LC-MS/MS method. The pharmacokinetic parameters were calculated by DAS 3. 0 software and the bio-equivalence was evaluated. Results:The maln pharmacokinetic parameters of the two formulations were shown as follows:T1/2 of (2. 20 ± 0. 83)h and(1. 951 ± 0. 515)h,Tmax of (3. 88 ± 1. 11)h and(4. 64 ± 1. 504)h,Cmax of (401. 06 ± 170. 75)ng·ml-1 and(394. 63 ± 215.64)ng·ml-1,AUC0→t of (918.42 ±427.39)ng·h·ml-1 and (994.49 ±520.73)ng·h·ml-1, and AUC0→∞ of(937.30 ± 445.13)ng·h·ml-1 and(1 011.69 ±534.77)ng·h·ml-1. The analysis showed that the maln pharmacokinetic parameters of the two formulations had no significant differences(P>0. 05) except for Tmax(P<0. 05). The relative bioavallability of rabeprazole sodium enteric-coated pellets capsules was (99. 80 ± 7. 20) %. Conclusion:Compared with the reference capsules, rabeprazole sodium enter-ic-coated pellets capsules show the property of higher dispersion degree, milder influence from food, more rapid release and absorption. The enteric-coated pellets capsules and the reference capsules are bioequivalence.
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Objective To investigate the therapeutic mechanism of umbilical cord mesenchymal stem cell(UC-MSCs)trans-plantation for the graves disease(GD)mice .Methods Thirty two mice were divided into 3 groups as following :normal control group (G0) ,GD control group (G1) ,UC-MSCs group(G2) .Enzyme linked immunosorbent assay(ELISA)was used to measure the level of TSAb in blood serum and the expression of FT4 was measured by chemiluminescence .Thyroid sections were stained with hema-toxylin and eosin(HE)for histological examination .Splenocytes were stained with multicolor immunofluorescence and detected by flow cytometry to analyze the percentages of CD1dhiCD5+CD19+ regulatory B cells(Bregs) .Expressions of IL-10 and TGF-βmR-NA in spleen organization were measured by Real-time PCR .Results At 26 weeks ,the level of TSAb in blood serum in G2 was more significantly decreased than in G1(P<0 .05) ,and the level of CD19+ B in spleen in G2 was also more significantly decreased than in G1(P<0 .05) ,however ,the percentage of CD1dhiCD5+CD19+ Bregs splenocytes and the levels of IL-10 and TGF-βmRNA in spleen organization were more significantly increased than in G1(P<0 .05) .The concentration differences of TSAb in serum was negatively correlated with the percentage differences of CD1dhi CD5+ CD19+ Bregs ,however ,positively correlated with the expres-sion differences of IL-10 and TGF-βmRNA in spleen before and after transplantation .Conclusion Activation of Bregs may be one of the mechanisms of UC-MSCs therapeutic effect on GD mice .
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Aim To investigate whether liver X recep- tors attenuate high glucose-induced apoptosis in H9C2 cells through inhibiting nuclear factor-NF-κB.Methods The lentiviral vector of LXRs was constructed and H9C2 cells cultured in high glucose were infected.The H9C2 cells were divided into 6 groups:control group (5.5 mmol·L -1 glucose),mannitol group(5.5 mmol ·L -1 glucose +27.5 mmol·L -1 mannitol),high glu-cose group(33 mmol·L -1 glucose),green fluorescent protein(GFP)group LXRαgroup,and LXRβgroup. The inhibition rate of H9C2 cells,the mRNA of Bax, Bcl-2,the protein content of NF-κB,Bax,Bcl-2, cleaved caspase-3,and the cell apoptosis were com-pared among these groups.Results LXRs overexpres-sion significantly attenuated high glucose-induced in-crease in Bax NF-κB,cleaved caspase-3 and cell ap-optosis(P <0.05),and increased high glucose-induced decrease in Bcl-2.Conclusion Liver X receptors at-tenuate high glucose-induced apoptosis in H9C2 cells through NF-κB signaling pathway.
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Batifiban, a synthetic cyclic peptide, is a potent platelet glycoprotein GPIIb/IIIa antagonist which may be useful in the treatment and prevention of acute coronary syndromes. The pharmacokinetics and pharmacodymanic (inhibition of platelet aggregation) effects, and tolerability of batifiban were investigated in healthy subjects following single bolus injection with doses of 55, 110, or 220 microg/kg, or multiple doses of an bolus followed intravenous infusion for 24 h (180 microg/kg plus 2.0 microg/min.kg, and 220 microg/kg plus 2.5 microg/min.kg) in this phase I clinical trial. Plasma levels of batifiban and areas under the curve were found to be proportional to doses. Batifiban was rapidly eliminated with a half-life of approximately 2.5 h. Significant differences were noted for plasma levels of batifiban and areas under the curve between males and females. No significant differences in the terminal half-life were found between males and females. Batifiban reversibly inhibited ex vivo platelet aggregation in a dose- and concentration-dependent manner, consistent with its mechanism as a GPIIb/IIIa antagonist. Single and multiple intravenous doses of batifiban were found to be safe and well tolerated in healthy subjects. These results support a bolus injection plus intravenous infusion regimen of batifiban for the treatment and prevention of acute coronary syndromes.
Subject(s)
Young Adult , Injections, Intravenous , Peptides, Cyclic/pharmacokinetics , Peptides, Cyclic/pharmacology , Platelet Aggregation Inhibitors/adverse effects , Platelet Aggregation Inhibitors/pharmacokinetics , Platelet Aggregation Inhibitors/pharmacology , Platelet Glycoprotein GPIIb-IIIa Complex/antagonists & inhibitorsABSTRACT
The current study was designed to determine the safety, tolerability and pharmacokinetic parameters of recombinant human parathyroid hormone [rhPTH (1-84)] used for the treatment of osteoporosis. In the single-dose format pharmacokinetic study, thirty-six healthy male volunteers received three dose levels of rhPTH (1-84) subcutaneously: 1, 2, and 4 mug/kg. The blood was timing drawn and the serum concentration of rhPTH (1-84) was determined by enzyme linked immunosorbent assay (ELISA). Serum concentration-time curves of PTH (1-84) exhibited a double-peak pattern, the first peak appearing about 10 to 30 min after administration and the second peak occurring about 1.5 to2 h after administration. Serum terminal half-time of PTH (1-84) was approximately 2 h. The parameters indicated the serum levels were directly proportional to the administered dose, with the mean C(max) and AUC(0-24) ranging from approximately 543.47 to 1845 pg/mL and 2358.6 to 9232.12 pg.h.mL(-1) over the dose range. The drug was well tolerated, the clinical symptoms were generally mild and of short duration.
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Objective To observe the therapeutic effects of recombinant human granulocyte colony stimulating factor(rhG-CSF)on CCl4 induced chronic liver injury.Methods Male BALB/C mice were randomly allocated into treatment and control groups.The mice model were established by injection with daily for 7 days,while the control mice were received the same volumes of saline.The mice were sacrificed to get weight,liver mass and spleen mass.The count of CD34+ cells and Thy-1+ cells were analyzed by flow cytometry and immunohistochemical staining,respectively.Results The ratio of liver/spleen was 15.94±1.20 and 10.52±0.66 on day 8 and 15 in treatment group,respectively,while those were 7.14±1.68 and 8.31±1.71 in control group,respectively(all P value＜0.05).But there was no significant difference in body weight and liver mass between two groups(P＞0.05)The concentration of album in treatment group was raised rapidly on day 15.The concentrations of alanine aminotransferase (ALT),aspartate aminotransferase(AST),hyaluronic acid(HA)and laminin(LN)on day 30 were significantly lower in treatment group compared to control group(P＜0.05).There was significant difference in score of liver fibrosis on day 30 between two groups(treatment group:5.49±2.16,control:8.74±1.86,P＜0.05).The number of CD34+ cell and Thy-1+ in treatment group(on day 8:9.54±2.24 and 5.10±1.25 and on day 15:8.18±1.93 and 7.53±1.39,respectively)were higher than those in control group(on day 8:5.40±0.99 and 3.25±0.75;on 15 days:4.46±0.77 and 3.35±0.86,all P value＜0.05).Conclusion The rhG-CSF may improve the reparation of chronic liver injury,and may provide a novel method in treatment of liver fibrosis.