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AIM: To study chronopharmacokinetics of helicid and its metabolites. METHODS: An HPLC-MS method for simultaneous determination of helicid and its three phase I metabolites were established and validated. At 8:00, 14:00 and 0:00, the rats were given helicid 50 mg/kg by gavage, respectively. Blood samples were collected from ophthalmic venous plexus. Then plasma concentration was measured. Pharmacokinetic behaviors of the original drug and its metabolites after administration at different time points were calculated and compared. RESULTS: This established HPLC-MS/MS method was successfully applied to simultaneous determination of helicid and its three metabolites in rat plasma after intragastric administration. Using AUC
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OBJECTIVE To investigate the effect of the dosing time on the pharmacokinetics of gefitinib and its potential mechanism. METHODS Female BALB/c nude mice were housed under standardized 12 h light/dark circadian conditions(light on at 7:00,off at 19:00)for two weeks before a non-small cell lung cancer(NSCLC)model was established. Two weeks later,they were divided into 2 groups(8:00,20:00)randomly. Gefitinib was orally administered at the dose of 1 mg · kg-1 to the mice in each group at 8:00 or 20:00,respectively. Blood was collected at 10 different time points after each administration. Livers were collected every 4 h during the 24 h period from the non-administrated nude mice of NSCLC model. The plasma concentration of gefitinib was determined through an HPLC-MS/MS and the parameters were calculated by WinNonlin 6.3. The total RNA was extracted from livers,purified, synthesized to cDNA that was subjected to qRT-PCR analysis for mRNA expression levels of cyto?chrome P450 enzymes(Cyp)3a11,Cyp3a13,pregnane X receptor(PXR)and constitutive androstane receptor (CAR). RESULTS The area under the plasma concentration-time curve (AUC) and mean residence time (MRT) of 8:00 administration group were higher than those of 20:00 administration group(P<0.05). The clearance(Clz/F) of 8:00 administration group was lower than that of 20:00 administration group(P<0.05). The mRNA expression levels of PXR and CAR were consistent with those of Cyp3a11 and Cyp3a13. CONCLUSION Circadian rhythm exists in the pharmacokinetics of gefitinib and it may be closely related to CYP3A and its regulator genes.
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Objective To explore propofol dosage difference between in morning and at after-noon undergoing gynecological clinic short operation.Methods One thousands and nine hundred fifty eight female patients,aged 1 6-50 yr,of ASA physical status Ior II,undergoing gynecology clinic short operation,according to the operation time,were divided into two groups,Group morning (8:30-1 1:30,n =1047)and group afternoon (14:00-1 7:00,n =91 1).Each patient was intravenously injected fentanyl 0.01 μg/kg,and then propofol 2.5 mg/kg.When the observer’s assessment of alertness/se-dation (OAA/S)scores reached 0 score,the operation began.If the body moved,the surgery was stopped and 25 mg propofol was intravenously injected quickly.After 10 seconds observation,if the body movement existed,25 mg more propofol was performed,until the movement disappeared.Re-cord patients’year,height,weight,body mass index,and the heart beat,blood pressure of pre-op-eration,the number of times of cervix uteri expansion per vagina,the history of labor per vagina,the total dosage of propofol and the time length of sedation.Results The dosage of group afternoon (1 52.1 6±65.90)mg was higher than group morning’s (135.69±37.67)mg (P <0.05).There was no significant difference of time lengths of sedation between the two groups.Additional use of propofol in the afternoon group 387 (42.5%)was higher than group morning’s 1 99 (23.5%)(P <0.05).Conclusion In gynecological clinic short operation,the propofol dosage in afternoon was higher than that in the morning group.But the sedation time length in afternoon was not longer than that in the morning.
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Aim To study effects of different dosage regimens of gentamicin(GTM) on impairment of renal functions, plasma concentrations and pharmacokinetics in rats. Method 108 rats were divided into 6 groups: control group; chronological once-daily dose groups (N100 and D100 group, in which 100 mg?kg -1 GTM were intramuscularly administrated at 01 ∶00 or 13 ∶[KG-*3]00 respectively), and chronological twice-daily different dose groups (N90+D10, N70+D30, N50+D50 group, in which 90 mg?kg -1+10 mg?kg -1, 70 mg?kg -1+30 mg?kg -1 and 50 mg?kg -1+50 mg?kg -1 GTM were given at 1:00 and 13:00 respectively). The blood urea nitrogen (BUN) and creatinine (Cr) levels were observed, the plasma concentrations of GTM at 0.25,0.5,1, 2, 5 and 8h were determined, the C-T curves were profiled and the pharmacokinetic parameters were calculated at the 1st, the 10th, and the 20th day of administrations. Results ① Impairment of renal function. At the 10th day of administration, the Cr and BUN levels of N50+D50 group were the highest. There was a significant difference when compared those of the 10th day of administration with those of the 1st day of administration and of control group at same time respectively (P