The combined use of batifiban, a synthetic platelet GPII b/ IIIa receptor antagonist, and antithrombin agents is an attractive option for the treatment of patients with non-ST-segment elevation (NSTE) acute coronary syndrome (ACS) and those scheduled for percutaneous coronary intervention. To observe whether antithrombin agents affect the pharmacokinetic and pharmacodynamic properties of batifiban in combination therapy and optimize clinical administration dosage of batifiban, an open-label and parallel study was conducted. Thirty healthy subjects were randomly divided into three groups, which were sequentially treated with batifiban alone, or oral coadministration of clopidogrel, aspirin and UFH, or batifiban coadministered with these antithrombin agents. Blood samples were collected at pre-specified time points. The evaluation index included the inhibition of platelet aggregation and pharmacokinetic parameters. The pharmacokinetic parameters of batifiban and batifiban coadministered with antithrombin agents showed no significant differences. The mean inhibition rate of platelet aggregation (%) suggested that neither batifiban alone nor antithrombin agents alone could provide such potent inhibition rate (>80%) to obtain the best clinical efficacy, but they had a synergistic effect on platelet inhibition. No serious adverse effects were observed. The results in these healthy subjects suggest that batifiban coadministrated with antithrombin agents could achieve optimum clinical treatment effect for patients with NSTE ACS, and also those scheduled for percutaneous coronary intervention.
Administration, Oral ; Adolescent ; Adult ; Area Under Curve ; Aspirin ; administration & dosage ; pharmacology ; China ; Drug Administration Schedule ; Female ; Fibrinolytic Agents ; administration & dosage ; pharmacology ; Heparin ; administration & dosage ; pharmacology ; Humans ; Infusions, Intravenous ; Injections, Intravenous ; Male ; Metabolic Clearance Rate ; drug effects ; Peptides, Cyclic ; administration & dosage ; pharmacokinetics ; Platelet Aggregation Inhibitors ; administration & dosage ; pharmacokinetics ; Ticlopidine ; administration & dosage ; analogs & derivatives ; pharmacology ; Time Factors ; Young Adult

OBJECTIVETo explore the effect of hemoperfusion (HP) on tylenol poisoned patients.

METHODSUrgently established the blood access by transfemoral catheterization of femoral vein, we used charcoal hemoperfusion by blood pump and dynamically monitored the plasma concentration of tylenol active ingredients for the 2 patients and the content of tylenol active ingredients in the charcoal was determined.

RESULTSPlasma concentration of tylenol active ingredients of the 2 patients was declined gradually during and after the HP management. The acetaminophen serum concentration of the case 1 was declined from the 13.4 µg/L at the start of HP to the 5.81 µg/L at the end of HP; and the case 2 was declined from 51.1 µg/L to 22.3 µg/L. The adsorption amount of acetaminophen in the blood perfusion device are respectively 119 542 µg of case 1 and 33 2154 µg of case 2.

CONCLUSIONEarly hemoperfusion should be carried out for acute tylenol poisoning patients if there were indications, hemoperfusion can clear the tylenol active ingredients and this is an effective measure to eliminate tylenol active ingredients.

Acetaminophen ; blood ; pharmacokinetics ; poisoning ; Adult ; Anti-Inflammatory Agents, Non-Steroidal ; blood ; pharmacokinetics ; poisoning ; Drug Overdose ; therapy ; Drug-Related Side Effects and Adverse Reactions ; blood ; Female ; Hemoperfusion ; Humans ; Metabolic Clearance Rate ; Young Adult

The plasma ghrelin has been reported to be elevated in Prader-Willi syndrome (PWS) and modulated by insulin. It was hypothesized that insulin might have a more pronounced effect on reducing plasma ghrelin in PWS patients, which would influence appetite. This study investigated the degree of ghrelin suppression using an euglycemic hyperinsulinemic clamp in children with PWS (n=6) and normal children (n=6). After a 90-min infusion of insulin, the plasma ghrelin level decreased from a basal value of 0.86+/-0.15 to 0.58+/-0.12 ng/mL in the controls, and from 2.38+/-0.76 to 1.12+/-0.29 ng/mL in children with PWS (p=0.011). The area under the curve below the baseline level over the 90 min insulin infusion was larger in children with PWS than in controls (-92.82+/-44.4 vs. -10.41+/-2.87 ng/mL/90 min) (p=0.011). The insulin sensitivity measured as the glucose infusion rate at steady state was similar in the two groups (p=0.088). The decrease in the ghrelin levels in response to insulin was more pronounced in the children with PWS than in the controls. However, the level of ghrelin was always higher in the children with PWS during the clamp study. This suggests that even though insulin sensitivity to ghrelin is well maintained, an increase in the baseline ghrelin levels is characteristic of PWS.
Prader-Willi Syndrome/*blood ; Peptide Hormones/*blood/*drug effects ; Metabolic Clearance Rate/drug effects ; Male ; Insulin/*administration & dosage/blood ; Infusions, Intravenous ; Humans ; Female ; Down-Regulation/drug effects ; Child ; Adolescent

The purpose of this study is to evaluate the interaction effects of In-Chen-How (Artemisia capillaries Thunb.) on the pharmacokinetics of acetaminophen and on liver microsomal cytochrome P450 enzyme activity in rats. The rats were divided into control group (n = 8) without In-Chen-How and the pretreated group (n = 8) administered with In-Chen-How (approximately 1.0 mL x kg(-1), according to weight) for 5 consecutive days. Rats in the control group received water simultaneously. Each rat was then given acetaminophen. The pharmacokinetic parameters of acetaminophen of the two groups were significantly different. In the In-Chen-How pretreated group, the maximum concentration of acetaminophen and the area under the plasma concentration-time curve were reduced about 58.4%, 56.7% and 55.4%. To further explain the results, liver microsomal suspensions were obtained from rats that were randomly divided into control and In-Chen-How pretreated group. The levels of CYP1A2 and CYP2E1 in hepatic microsomal protein from pretreated group were increased as compared to that from the control group. It indicated that In-Chen-How can stimulate the activity of CYP isozymes. The changes in the pharmacokinetics of acetaminophen resulting from the administration of In-Chen-How are related to an increase in metabolic activity of CYP1A2 and CYP2E1.
Acetaminophen ; administration & dosage ; blood ; pharmacokinetics ; Administration, Oral ; Analgesics, Non-Narcotic ; administration & dosage ; blood ; pharmacokinetics ; Animals ; Area Under Curve ; Artemisia ; chemistry ; Aryl Hydrocarbon Hydroxylases ; metabolism ; Cytochrome P-450 CYP1A2 ; metabolism ; Cytochrome P-450 CYP2E1 ; metabolism ; Drug Interactions ; Drugs, Chinese Herbal ; isolation & purification ; pharmacology ; Immunoblotting ; Male ; Metabolic Clearance Rate ; drug effects ; Microsomes, Liver ; drug effects ; enzymology ; Plants, Medicinal ; chemistry ; Random Allocation ; Rats ; Rats, Wistar

OBJECTIVETo investigate the relationship between peak concentration (Cmax) of gemcitabine at fixed-dose-rate and its hematological toxicity profile in patients with advanced non-small-cell lung cancer (NSCLC).

METHODSTwenty-one patients received gemcitabine at a fixed dose rate (1200 mg/m2 over 120 min) with carboplatin. Plasma concentrations of gemcitabine were measured by ion-pair reversed-phase high-performance liquid chromatography.

RESULTSThe mean value of Cmax in 21 eligible patients was(4.95+/-2.42) microg *ml(-1). The main hematological toxicity was grade III-IV thrombocytopenia and neutropenia. The mean percentages of reduction of WBC, NEC, PLTC and Hb of 21 patients were (38.3+/-38.1)%, (31.3+/-73.6)%, (31.8+/-53.5)% and (12.0+/-12.2)%, respectively. The C(max)of gemcitabine and the percentage of reduction in WBC showed a significant correlation (r2=0.4575, P<0.05). A significant correlation (r2=0.5671, P<0.05) was also observed between the percentage of reduction of PLTC and Cmaxof gemcitabine.

CONCLUSIONThe results of relationship between Cmax and toxicity profile suggest that gemcitabine administration should be individualized in order to decrease the occurrence of ADR.

Adult ; Aged ; Antimetabolites, Antineoplastic ; administration & dosage ; adverse effects ; pharmacokinetics ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; pharmacokinetics ; therapeutic use ; Carboplatin ; adverse effects ; blood ; pharmacokinetics ; Carcinoma, Non-Small-Cell Lung ; drug therapy ; metabolism ; Chromatography, High Pressure Liquid ; Deoxycytidine ; adverse effects ; analogs & derivatives ; blood ; pharmacokinetics ; Female ; Humans ; Infusions, Intravenous ; Lung Neoplasms ; drug therapy ; metabolism ; Male ; Metabolic Clearance Rate ; Middle Aged ; Neutropenia ; chemically induced ; Thrombocytopenia ; chemically induced

OBJECTIVEThe metabolic character of tetramethylpyrazine (TMPz) in rat liver microsomes was studied in vitro and in vivo to identify which isoforms of cytochrome P450 were responsible for TMPz metabolism in rats, offer the theoretical foundation for the fact that it is rational to use medicine in clinic.

METHODSet up UV- HPLC method of TMPz, determine concentration of TMPz and its formation in rat plasma and liver microsomes incubation solution, analyze the correlation between TMPz's metabolic eliminate rate and each inducer. Erythromycin( ERY) N-demethylase activity of each sample in rat liver microsomes was measured using N-demethylation reaction of ERY as probe. The correlation between the rate of TMPz metabolite formation and the demethylase activity was analysed. After the SD rats who had been treated with inducer, inhibitor, or untreated, received administration of TMPz in vein, the plasma concentration of TMPz were determined by HPLC. Pharmacokinetic parameters of TMPz were computed and compared.

RESULTThe disppearing rate of TMPz in the incubation solutions of the rats liver microsomes, which treated with DEX, were markedly quicker than that of control group (P < 0. 01) , while no obvious difference between P-NF group or PB and control group was observed (P > 0. 05). The activity of ERY-N-demethylase in DEX-induced group was corespondingly enhanced, was much higer than that in control group. The correlation between the rate of TMPz metabolic product formation and the activity of N-demethylase was significant. After using Ket, the CYP3A inhibitor, the metabolism of TMPz could be significantly inhibited the metabolism of TMPz in rat liver microsomes. In vivo, CL( s) were larger than that of the control group,t,/2 were smaller than the control group in DEX group; By contrary, CL(s) was smaller than the control group,t1/2 was larger than the control group in Ket group.

CONCLUSIONResults suggest that CYP3A plays a major role in TMPz metabolism in rats, TMPz lie in the possibility of Interaction among the medicines between TMPz and CYP3A inducers or inhibitors when they are used in clinic.

Animals ; Cytochrome P-450 CYP3A ; metabolism ; Cytochrome P-450 CYP3A Inhibitors ; Dexamethasone ; pharmacology ; Ketoconazole ; pharmacology ; Male ; Metabolic Clearance Rate ; Microsomes, Liver ; drug effects ; enzymology ; metabolism ; Pyrazines ; blood ; metabolism ; pharmacokinetics ; Random Allocation ; Rats ; Rats, Wistar ; Vasodilator Agents ; blood ; metabolism ; pharmacokinetics

AIMTo explore the intestinal absorption characteristics of lumbrokinase (YJM-I) in the absence or presence of various absorption enhancers and to find the optimum intestinal site for YJM-I absorption.

METHODSThe absorption kinetics and absorption intestinal sites for YJM-I absorption were investigated with the method of diffusion cell in vitro, duodenum bolus injection, recirculating perfusion and in situ duodenum perfusion in vivo.

RESULTSYJM-I could be transported into blood and kept its biological activity across intestinal endothelial membrane after administration via duodenum site, whereas with lower bioavailability. Some of the absorption enhancers were shown good enhancement effects on intestinal absorption of YJM-I in vitro and in situ experiments. The order of enhanced efficiencies of various enhancers on duodenum, ileum and jejunum in vitro permeation experiments were shown as follows: 1% chitosan > 1% SDCh > 1% Na2EDTA > 1% SDS > 1% sodium caprylate > 1% poloxamer > 1% HP-beta-CD. The order of enhanced efficiencies of various enhancers on duodenum absorption of YJM-I in vivo were as follows: 2.5% SDCh > 2.5% Na2EDTA > 2.0% chitosan > 2.5% SDS > 2.5% sodium caprylate > 2.5% Poloxamer > 2.5% HP-beta-CD.

CONCLUSIONThe results indicated that the absorption of YJM-I could be enhanced by various enhancers, and duodenum was the optimum absorption site of YJM-I. Furthermore, bio-adhesive chitosan might be a potential enhancer of intestinal YJM-I absorption.

Administration, Oral ; Animals ; Area Under Curve ; Caprylates ; pharmacology ; Chitosan ; pharmacology ; Deoxycholic Acid ; pharmacology ; Duodenum ; drug effects ; metabolism ; Edetic Acid ; pharmacology ; Endopeptidases ; administration & dosage ; pharmacokinetics ; Injections, Intravenous ; Intestinal Absorption ; Male ; Metabolic Clearance Rate ; Poloxamer ; pharmacology ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo observe the incidence of elimination delay in high dose methotrexate (HDMTX) therapy, its side effects and influence to next course of chemotherapy and analyze the relationship between the dosage, the duration of MTX infusion and the morbidity of the elimination delay.

METHODSA total of 121 childhood acute lymphoblastic leukemia (ALL) (497 infusions of HDMTX) were analysed in this study. The elimination delay rate and the adverse effects in different dose groups (3 g/m2 vs 5 g/m2) and different infusion duration groups (7 h vs 24 h) were compared. The adverse effect evaluation was based on the World Health Organization (WHO) Toxicity Grading Criteria. The rescue dosages of calcium folinate (CF) among these groups were compared through CF/MTX index.

RESULTSThe overall morbidity of elimination delay was 12.1% with a relative risk of 30.6% for the first time. The relative risk for the second time of occurrence was increased to 45.9% (P < 0.01) and it was not significantly increased for the third time (35.3%). Children with elimination delay had lower platelet count (P < 0.01) and higher CF rescue dosage (P < 0.01), while the damage of oral mucous membrane was more severe (P < 0.05) and the next course of chemotherapy would be postponed for a median of 4 days in 3 g group. There was no significant difference in elimination delay rates between 3 g and 5 g groups (12.1% vs 12.0%, P > 0.05), and between 7 h and 24 h MTX infusion groups (13.6% vs 11.9%, P > 0.05). The only side effect occurred in 5 g group was gastrointestinal morbidity. The CF/MTX index of 5 g group without elimination delay was less than that of 3 g group (P < 0.01).

CONCLUSIONElimination delay in HDMTX therapy accompanies the suppression of bone marrow and damage of oral mucous membrane, which need more CF rescues and will postpone the following course of chemotherapy. Elimination delay is not associated with the duration of the infusion and the dosage of MTX within the range of 3 approximately 5 g/m2 but there are individual differences.

Adolescent ; Antimetabolites, Antineoplastic ; adverse effects ; pharmacokinetics ; therapeutic use ; Child ; Child, Preschool ; Dose-Response Relationship, Drug ; Female ; Humans ; Infant ; Male ; Metabolic Clearance Rate ; Methotrexate ; adverse effects ; pharmacokinetics ; therapeutic use ; Nausea ; chemically induced ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; drug therapy ; Retrospective Studies ; Treatment Outcome ; Vomiting ; chemically induced ; Young Adult

To determine the loading and maintenance dosage of glutathione (GSH) for patients suffering from reactive oxygen species (ROS) injury such as acute paraquat intoxication, a kinetic study of reduced GSH was performed in synchrony with that of cysteine (Cys), cystine (Cys2), and methionine (Met). Human subject's porticipitation was voluntary. The effective dose of Cys, Cys2, and Met against ROS in fibroblast cells generated by paraquat was assessed using laser scanning confocal microscopy. Both Cys and Met suppressed ROS in a dose-dependent manner at concentrations of 1-1,000 micrometer; the concentration required to suppress ROS by 50% was 10 micrometer for Cys and 50 micrometer for Met. Using metabolite kinetics with the assumption that Cys and Met are the metabolites of GSH, expected concentrations of Cys and Met of above 20 and 50 micrometer were estimated when GSH was administered at 50 mg/kg body weights every 205.4 min for Cys and 427.4 min for Met.
Adult ; Amino Acids/*blood ; Animals ; Dose-Response Relationship, Drug ; Glutathione/administration and dosage/*blood/*pharmacokinetics ; Humans ; Kinetics ; Male ; Metabolic Clearance Rate/drug effects ; Mice ; Reactive Oxygen Species/*metabolism ; Research Support, Non-U.S. Gov't ; Swiss 3T3 Cells

This study examines the possibility of using live spirulina to biologically remove aqueous lead of low concentration (below 50 mg/L) from wastewater. The spirulina cells were first immersed for seven days in five wastewater samples containing lead of different concentrations, and the growth rate was determined by light at wavelength of 560 nm. The 72 h-EC50 (72 h medium effective concentration) was estimated to be 11.46 mg/L (lead). Afterwards, the lead adsorption by live spirulina cells was conducted. It was observed that at the initial stage (0-12 min) the adsorption rate was so rapid that 74% of the metal was biologically adsorbed. The maximum biosorption capacity of live spirulina was estimated to be 0.62 mg lead per 10(5) alga cells.
Bacterial Proteins ; drug effects ; metabolism ; physiology ; Biodegradation, Environmental ; Cell Proliferation ; drug effects ; Cell Survival ; drug effects ; Dose-Response Relationship, Drug ; Feasibility Studies ; Lead ; administration & dosage ; isolation & purification ; pharmacokinetics ; Metabolic Clearance Rate ; Spirulina ; Water Pollutants, Chemical ; administration & dosage ; pharmacokinetics ; Water Purification ; methods