Anemarrhena asphodeloides Non-Steroidal Saponin Components Alter the Pharmacokinetic Profile of Its Steroidal Saponins in Rat
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A rapid, selective and sensitive UPLC-MS/MS assay was established to determine the plasma concentrations of four steroidal saponins. Sprague-Dawley rats were allocated to four groups which were orally administered Anemarrhena asphodeloides extracts (ASE), ASE combined with macromolecular fraction (ASE-MF), ASE combined with small molecule fraction (ASE-SF) and ASE combined with small molecule and macromolecular fraction (ASE-SF-MF) containing approximately the same dose of ASE. At different time points, the concentration of timosaponin BII, anemarsaponin BIII, timosaponin AIII and timosaponin E1 in rat plasma were determined and main pharmacokinetic parameters including Cmax, Tmax, T1/2, AUC were calculated using the DAS 3.2 software package. The statistical analysis was performed using the Student’s t-test with p < 0.05 as the level of significance. MF had no effect on the pharmacokinetic behaviors and parameters of four steroidal saponins. It was found that Cmax and AUC of four steroidal saponins in group ASE-SF and ASE-SF-MF, were significantly increased compared with those in group ASE. These results indicate that SF in A. asphodeloides extracts could increase the absorption and improve the bioavailability of the steroidal saponins.OBJECTIVE To study the pharmacokinetics of the resveratrol(RES)polyphase liposomes in rabbits after oral administration.METHODS Plasma concentrations of resveratrol in rabbits after oral administration were determined by HPLC.The pharmacokinetics parameters were calculated by 3P97.RESULTS Plasma concentration-time curves of RES and RES polyphase liposomes were both fitted to two-compartment model.The pharmacokinetics parameters of RES polyphase liposomes were calculated as follows:t1/2β=(4.37±0.34)h,AUC0→3=(4.6±0.6)mg·h·L-1,CL=(22.0±2.8)L·kg-1·h-1,Cmax=(3.10±0.07)mg·L-1.The pharmacokinetics parameters of RES solution as follows:t1/2β =(1.07±0.20)h,AUC0→3=(0.97±0.04)mg·h·L-1,CL=(103.3±4.0)L·kg-1·h-1,Cmax =(1.030±0.021)mg·L-1.There were significant difference between RES solution and RES polyphase liposomes.CONCLUSION Our present study demonstrates that compared to RES solution,RES polyphase liposomes significantly alters its pharmacokinetics in rabbits.It can raise AUC and prolong the t1/2βand increase Cmax and reduce CL of RES in the plasma of rabbits.
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OBJECTIVE:To study the pharmacokinetics of single oral dose of tinidazole tablet in Muslim and Han healthy volunteers.METHODS:Twenty volunteers(10 Muslim and 10 Han volunteers,with the ratio of male:female at 1∶1),Each subject received a single dose of 1 g tinidazole tablet.The plasma concentrations of tinidazole were determined by HPLC.The pharmacokinetics parameters were treated by DAS software and analyzed statistically by SPSS software.RESULTS:The main pharmacokinetics parameters of Muslim were as follows:Cmax(20.25±4.05)μg·mL-1,tmax(2.10±0.66)h,t1/2(16.81±1.56)h,AUC0～72(483.51±116.83)mg·h·L-1,and AUC0～∞(514.25±130.78).The main pharmacokinetics parameters of Han were as follows:Cmax(19.04±2.42)μg·mL-1,tmax(2.15±0.47)h,t1/2(16.94±2.40)h,AUC0～72(454.37±59.74)mg·h·L-1 and AUC0～∞(486.14±65.63)mg·h·L-1.The main pharmacokinetics parameters of Male were as follows:Cmax(17.16±1.28)μg·mL-1,tmax(2.20±0.59)h,t1/2(17.32±1.97)h,AUC0～72(406.83±44.40)mg·h·L-1 and AUC0～∞(437.11±54.73).The main pharmacokinetics parameters of Female were as follows:Cmax(22.12±2.79)μg·mL-1,tmax(2.05±0.55)h,t1/2(16.43±1.97)h,AUC0～72(531.05±84.54)mg·h·L-1 and AUC0～∞(563.27±100.06)mg·h·L-1.CONCLUSION:The results showed that the main pharmacokinetics parameters of tinidazole have no significant differences between Muslim and Han,but have significant differences between male and female.
Tinidazole
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Bioequivalence
Volunteer
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OBJECTIVE To investigate the pharmacokinetics of single dose and multiple dose of fudosteine tablets in chinese healthy volunteers.METHODS 12 volunteers were divided into three groups and fudosteine concentrations in plasma of 12 volunteers after taking 200,400 and 600 mg fudosteine and taking multiple 400 mg fudosteine were determined by LC-MS.The pharmacokinetic parameters were calculated by DAS 2.0 software.RESULTS The main pharmacokinetics parameters of single dose:Cmax were 8.8±4.2,19.4±4.0 and 33.6±11.5 mg·L-1,respectively;AUC0-t were 15.6±3.7,30.4±6.5and 55.3±9.0 mg·h·L-1,respectively;tmax were 0.44±0.15,0.54±0.34 and 0.46±0.12 h,respectively;t1/2 were 3.1±0.6,3.0±0.5 and 2.65±0.33 h,respectively,CL/F were 12.7±3.2,12.5±2.4 and 10.7±1.7 h-1,respectively.The main pharmacokinetics parameters Cmax,AUC0-t,AUC0-∞ showed direct proportion to doses.There were no singnificant difference in tmax,Ke,t1/2,MRT and CL/F of three groups.The parameters of multiple dose:Cmax was 18.7±5.8 mg·L-1;AUC0-t and AUC0-∞ were 29.3±11.0 mg·h·L-1 and 31.1±11.9 mg·h·L-1,respectively;t1/2 was 3.1±0.5 h;Css was 2.4±0.9 mg·L-1;and DF% was(7.8±2.2)%.CONCLUSION The pharmacokinetics of fudosteine between 200 mg and 600 mg in human body was linear.There was no drug accumulation after taking multiple dose.
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The bioavailabilities of five indomethacin capsules were studied in ten beagle dogs and correlations with the in vivo results in humans and dissolution rates were investigated. The difference in bioavailability between two commercial products was smaller in dogs than in humans, which seemed to be due to strong disintegration forces in dogs. The difference in the dissolution rate among the products was reflected less in the Tmax in dogs than in humans, and the Tmax was shorter in dogs which seems to be due to faster gastric emptying and passage of the drug through the absorption site in dogs. Gastric acidity effects on the indomethacin availability found in humans were not observed in dogs. The Cmax and Tmax correlated well with the in vitro dissolution rates, but AUC24 did not. The Cmax and Tmax in dogs also correlated with the corresponding parameters in humans, especially those in high gastric acidity humans, but AUC24 did not.
Beagle
Gastric fluid
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The bioavailability of nalidixic acid in beagles was determined using the same tablet formulations previously tested on humans and was compared with bioavailability in humans and with in vitro dissolution rates. The beagle bioavailability test provided lower power in all of the bioavailability parameters than did the human test. Tmax of the tablets did not greatly differ in beagles, although in humans a wide variation of Tmax was seen. A linearity between Cmax and AUC0-infinity was observed in beagles, but Tmax did not show a linearity with Cmax or AUC in dogs, which is quite different from the relations observed in humans. The rank order of tablets according to Cmax was exactly the same between humans and beagles. AUC also showed the same rank order between humans and beagles except for on tablet with a poor disintegrating ability. A significant correlation between human and beagle Cmax values was obtained (r = 0.8952; p less than 0.05), but not between human and beagle AUC and Tmax values.
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Forty healthy male Caucasian volunteers were randomly assigned to five treatment groups to receive a placebo or a 4, 8, 12, 16 or 20 mg dose of nilvadipine. The drug was well tolerated by the subjects at all dose levels. Pharmacokinetic parameters for nilvadipine were determined using model-independent methods. There were no significant differences (p greater than 0.05) in the time to the maximum plasma concentration (Cmax) (tmax), the elimination half-life or the mean residence time among the five treatment groups. Up to doses of about 12 mg, there was a linear relationship between dose and Cmax or area under the plasma concentration-time curve (AUCO----infinity). At doses of 16 and 20 mg, the relationship between dose and Cmax or AUCO----infinity was no longer linear, suggesting that the pharmacokinetics of the drug after single oral doses greater than about 12 mg may be dose-dependent, probably due to concentration-dependent first-pass hepatic elimination of the drug.
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Objective:To investigate the pharmacokinetics and pharmacodynemics of Pazufloxacin mesilate injection.Methods:Twelve healthy volunteers were administrated 500mg Pazufloxacin mesilate single and multiple-doses intravenously.The plasma and urine concentrations were determined by RPHPLC-UV method and the pharmacokinetic parameters were calculated by DASver1.0 software.Rusults:The pharmacokinetics of pazufloxacin is fit to two compartment model.The pharmacokinetic parameters after single administration:Tmax was 0.47±0.09h,Cmax was 13.71±1.81mg/L,AUC0-t was 24.60±4.15mgh/L,T1/2 was 1.46±0.64h.The pharmacokinetic parameters after successive administration:Tmax was 0.48±0.10h,Cmax was 15.41±1.67mg/L,AUC0-t was 8.42±4.90mg·h/L,T1/2 was 1.33±0.49h,(Css)av was 2.34±0.43mg/L,DF was 99.48±0.38%.There were no significant differences in all pharmacokinetic parameters except Cmax between the first and the last administraion of Pazufloxacin and cumulation coefficient was very small.That indicates there may have no accumulation after successive administration.No serious adverse effect was observed in volunteers.Conclusion:Effective concentration in vivo could achieved after intravenous infusion of 500mg Pazufloxacin mesilate twice a day and there may have no accumulation in human body for 5 days administration.The dosing schedule was recommended.
Pharmacodynamics
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Pharmacokinetics of etoposide in Japanese children and adolescents has not been investigated. The objectives of the present study were (i) to document the pharmacokinetics of etoposide in Japanese children; (ii) to determine the intra- and interpatient variability in systemic etoposide exposure and (iii) to obtain insights into the age-pharmacokinetic parameter relationship.Pharmacokinetic studies of etoposide, given at doses of 60-200 mg/m2 by intravenous (i.v.) route of administration, were conducted in 18 children and adolescents (aged <19 years) with malignant diseases. High performance liquid chromatography was used to measure the blood etoposide levels.Pharmacokinetic parameters (mean~SD) of the 14 patients (24 courses) who received etoposide 100 mg/m2 were as follows: peak serum concentration (Cmax), 18.5~6.4 microg/mL; trough serum concentration, 0.2~0.1 microg/mL; biological half-life (T1/2), 3.6~0.7 h; volume of distribution (Vd), 6.3~3.4 L/m2; area under the etoposide serum concentration-time curve (AUC), 129~38 hr x microg/mL; systemic clearance, 21.1~10.8 mL/min per m2. The T1/2, Vd, and AUC were not associated with age. An increase in etoposide dose per body surface area (BSA) was associated with increase in its Cmax and area under the time-concentration curve (AUC). Wide interpatient variability in these parameters was demonstrated.The present study demonstrated that: (i) Pharmacokinetics of etoposide in Japanese children and adolescents were similar to those in Caucasians. (ii) Increased exposure to etoposide was associated with the Cmax. A clear correlation between Cmax and AUC was also found. (iii) Selecting the dose of etoposide according to body surface area (BSA) might give an acceptable range of exposure for children more than 1 year of age.
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OBJECTIVE To study the pharmacokinetics of lansoprazole for injection in Chinese healthy volunteers.METHODS 30 healthy volunteers were randomly into 3 groups,with 5 males and 5 females in each group.The volunteers in three groups were administrated with single dose of lansoprazole 15,30,and 60 mg,respectively.Those who got the dose of 30 mg were administrated twice daily till 5th day.The concentrations of lansoprazole in plasma were determined by LC-MS/MS while the pharmacokinetics parameters were calculated by DAS software.RESULTS The main pharmacokinetic parameters of lansoprazole after single-dose IV administration were as follows: tmax(0.67±0.00),(0.67±0.00),(0.73±0.09)h;Cmax(857.1±251.2),(1 738.5±263.8),(3 609.4±421.6)μg·L-1;AUC0-12(2 873.9±2 065.4),(3 366.2±1 138.9),(12 321.1±5 632.5)μg·h·L-1;t1/2(2.5±1.8),(1.4±0.4),(3.0±1.8)h.The main pharmacokinetic parameters of lansoprazole after multiple-dose administration were as follows: tmax(0.70±0.07)h;Cmax(1 530.2±305.1)μg·L-1;AUC0-12(3 048.1±1 181.0)μg·h·L-1;AUCSS(3 048.1±1 181.0)μg·h·L-1;t1/2z(1.3±0.3)h;CLz(11.0±4.1)L·h-1;Cav(254.0±98.4)μg·L-1.CONCLUSION Lansoprazole for injection displays linear pharmacokinetics in the dose range of 15 to 60 mg after single intravenous doses.No significant differences between genders are observed.There is no significant accumulation of lansoprazole in healthy volunteers with repeated dosing.
Lansoprazole
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