A pharmacokinetics study on Oxiracetam in rats. (II): Plasma levels profile, tissue distribution, metabolism and excretion during and after the repeated oral administration.
Hiroka SHIGETOHSatoru YamagamiKazuo UNONoriyasu TakayanagiYoshio ESUMIYoshitaka JinAtsushi TAKAOHitoshi ShimizuTomoko KawakamiNaomi SHIRAMIZU
1
Citation
2
Reference
10
Related Paper
Abstract:
The absorption, distribution, metabolism and excretion of Oxiracetam (CT-848) were studied in male rats during and after the consecutive oral administration of 10mg/kg of 14C-CT-848 for 14 days. 1. The plasma concentrations of radioactivity at 1hr and 6hr after each dose were not affected by repeated administration. After the 14th doses, radioactivity in plasma reached Cmax at 1hr and decreased with a half-life of 1.6hr (2 ?? 8 hr). 2. The concentrations of radioactivity in tissues at 6hr were not significantly different between after 7th and 14th doses and 1st dose. The elimination of radioactivity from tissues was rapid after the 14th dose. Accumulation of radioactivity in tissues was not observed. 3. The extents of excretion in urine and feces during consecutive oral do sing were 27.2 ?? 31.3%, and 52.7?? 72.1%, respectively. The elimination of radioactivity from the body was completed by 48hr after the final administration. 4. After repeated oral administration to non-fasting male rats, only unchanged compound was observed in plasma at 1hr and 6hr. In urine and feces up to 24hr after 1st and 14th doses only about 1 % of the recovered radioactivity was corresponded to unknown metabolites and the remainder was unchanged compound.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
Cite
Citations (0)
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.
Polyphase system
Cite
Citations (0)
Abstract The aim of this study was to assess the linearity of pharmacokinetic of alfuzosin, administered by oral route, at the doses of 1, 2·5, and 5 mg to 12 young healthy volunteers. The pharmacokinetic parameters ( t max , C max , AUC, t 1/2β ) obtained from plasma alfuzosin concentrations after administration of the three doses show that pharmacokinetics of alfuzosin is linear in the range of doses 1–5 mg. Mean pharmacokinetic parameters of alfuzosin observed after 1, 2·5, and 5 mg were, respectively: t max (h) 1·5±0·3, 1·1±0·2, 1·3±0·1; C max (ng ml −1 ) 2·6±0·3, 9·4±1·2, 13·5±1·0; AUC (ng ml −1 h) 17·7±2·9, 51·7±7·1, 99·0±14·1; t 1/2 (h) 3·7±0·4, 3·9±0·2, 3·8±0·3. C max (corrected by the dose) obtained after 2·5 mg was significantly higher than those obtained after 1 and 5 mg. This difference seems to be due principally to the intraindividual variability. The absence of statistically significant difference on individual values of AUC corrected by the administered dose, supports the linearity of the pharmacokinetics of alfuzosin in the range of doses between 1 and 5 mg. Some postural hypotension, clinical criterion, was observed with a frequency increasing with the dose in these healthy subjects: 0 volunteers of 12 after 1 mg, 3 volunteers of 12 after 2·5 mg and 4 volunteers of 12 after 5 mg.
Alfuzosin
Cite
Citations (8)
Abstract Objectives . The objective of this study was to examine the pharmacokinetics of orally administered omeprazole in healthy adult Jordanian men. Method . Plasma concentrations of omeprazole were measured over a 12 h period after administration of a single oral dose of 40 mg omeprazole (Losec ® , AstraZeneca, UK). Subjects were healthy adult Jordanian men age 18–38 (24±4, mean±SD). The pharmacokinetic parameters were derived from the plasma concentration‐time profiles for AUC 0‐t , AUC 0‐inf , C max , t max , t 1/2e and K e . Results . The pharmacokinetic of omeprazole were scattered over a wide range. The median AUC 0‐inf was 784.86±1182.88 (ng·h/ml), and the median C max was 521±354 (ng/ml) (median±SD). In general, most subjects showed normal distribution (∼90%). Some subjects (10%) did show very high AUC and C max compared with the reported AUC and C max levels. These subjects had higher half‐lives and lower rates of elimination. Conclusion . Significant difference in the pharmacokinetics of omeprazole after a single dose administration was noted. Approximately 10% of the study group showed very high omeprazole plasma levels and AUC s. Differences in the pharmacokinetics might be due to differences in the genetic make‐up of subjects. Copyright © 2005 John Wiley & Sons, Ltd.
Cite
Citations (1)
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.
Cite
Citations (0)
Objective To determine the pharmacokinetic parameters of 2 epimers of glycyrrhizic acid (GL) after oral administration of α-GL and β-GL in rats.Methods α-GL and β-GL solvent were administered orally at a dose of 25 mg·kg-1.The concentration in the plasma was measured by HPLC method.Experimental data and the pharmacokinetic parameters were processed with the computer program DAS 2.0 and SPSS.Results The main pharmacokinetic parameters were:AUC0-36=(57.04±14.64)μg·mL-1·h;Cmax= (4.68±2.56)μg·mL-1 t1/2=(5.56±1.65)h,tmax=(10.0±4.0)h after oral administration of α-GL;AUC0-36=(36.55±13.18)μg·mL-1·h;Cmax=(4.24±1.69)μg·mL-1,t1/2=(7.88±2.40)h,tmax=(9.0±1.1)h respectively after oral administration of β-GL.Conclusion The main pharmacokinetic parameters of GA after the oral administration of α-GL and β-GL are different.
Epimer
Oral dose
Cite
Citations (0)
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
Cite
Citations (0)
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.
Half-life
Oral dose
Cite
Citations (4)
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.
Cite
Citations (22)
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
Cite
Citations (0)