OBJECTIVETo investigate toxicokinetic parameters impacted by hemoperfusion after oral chlorpyrifos exposure, to investigate the adsorption effect of hemoperhusion for chlorpyrifos poisoning.

METHODS12 rabbits were divided into two groups after oral exposure with chlorpyrifos 300 mg/kg body weight. Control group: without hemoperfusion; hemoperfusion group: hemoperfusion starts 0.5 h after chlorpyrifos exposure and lasts for 2h. Blood samples were collected at different times, concentrations of chlorpyrifos were tested by GC, then, toxicokinetic parameterswere calculated and analysis by DAS3.0.

RESULTSIn hemoperfusion group, peak time was (7.19±3.74) h, peak concentrations was (1.37±0.56) mg/L, clearance rate was (13.93±10.27) L/h/kg, apparent volume of distribution was (418.18±147.15) L/kg The difference of these parameter were statistically significant compared with control group (P<0.05).

CONCLUSIONHmoperfusion will decrease the inner exposure and load dose of rabbits with chlorpyrifos poisoning.

Hemoperfusion ; Humans ; Metabolic Clearance Rate ; Paraquat ; blood ; pharmacokinetics

For the pharmacokinetic analysis of isoniazid transfer into CSF, steady-state isoniazid concentrations of plasma and CSF were measured in eleven tuberculous meningitis patients confirmed with findings of CSF and neuroimazing. Peak plasma levels (4.17-21.5 micrograms/mL) were achieved at 0.25 to 3 hours after multiple isoniazid dose (600 mg/day). Terminal half-life, total clearance (CI/F) and volume of distribution (Vd/F) were 1.42 +/- 0.41 hr, 0.47 +/- 0.22 L/kg/hr and 0.93 +/- 0.48 L/kg, respectively. Isoniazid concentrations in CSF collected intermittently were highest at 3 hr (Mean, 4.18 micrograms/mL) and were 0.54 +/- 0.21 micrograms/mL at 12 hrs after the last dose of isoniazid 10 mg/kg/day. CSF/plasma partitioning of isoniazid and equilibration rate were estimated using modified pharmacokinetic/pharmacodynamic model. Disposition rate constant from CSF to plasma and CSF/plasma partitioning ratio of isoniazid were estimated to be 0.39 h-1 and 1.17, respectively.
Administration, Oral ; Humans ; Isoniazid/*cerebrospinal fluid ; Metabolic Clearance Rate ; Models, Biological ; Tuberculosis, Meningeal/*cerebrospinal fluid

The reasonable prediction of metabolic clearance rate from the humanized in vitro system is valuable in drug discovery, which is commonly used in the identification and optimization of compounds that mostly like to process appropriate pharmacokinetic characteristics in humans. A detailed development of the general theory and, models underlying the prediction of in vivo hepatic drug metabolism from in vitro data were presented. Furthermore, the accuracy when extrapolating from in vitro data considering the in vitro-in vivo correlation, method-logical issues and potential solutions were discussed as well. This review can give us a better insight into exploring methods whereby human clearance can be accurately predicted from in vitro data in the process of new drug development.
Animals ; Humans ; Metabolic Clearance Rate ; Microsomes, Liver ; metabolism ; Models, Biological ; Pharmaceutical Preparations ; metabolism ; Pharmacokinetics

The key to the treatment of septic shock is to provide adequate oxygen supply and improve tissue perfusion. Lactate and central venous oxygen saturation (ScvO) are commonly used as the indices of oxygen metabolism, but tissue hypoxia may still exist even when lactate and ScvOare within the normal range. Arteriovenous difference in carbon dioxide partial pressure (COgap) can accurately reflect oxygen delivery when ScvOis in the normal range. This article reviews the advantages and shortages of lactate, lactate clearance rate, ScvO, and COgap in evaluating tissue hypoxia, in order to provide a reference for treatment and severity evaluation of septic shock.
Carbon Dioxide ; blood ; Humans ; Lactic Acid ; metabolism ; Metabolic Clearance Rate ; Oxygen ; blood ; Shock, Septic ; metabolism

We investigated the disposition kinetics and urinary excretion of cefpirome in buffalo calves after a single intravenous administration of 10 mg/kg. Also, an appropriate dosage regimen was calculated. At 1 min after injection, the concentration of cefpirome in the plasma was 57.4 +/- 0.72 microgram/ml, which declined to 0.22 +/- 0.01 microgram/ml at 24 h. The cefpirome was rapidly distributed from the blood to the tissue compartment as shown by the high distribution coefficient values (8.67 +/- 0.46/h), and by the drug's rate of transfer constant from the central to the peripheral compartment, K12 (4.94 +/- 0.31/h). The elimination halflife and the volume of distribution were 2.14 +/- 0.02 h and 0.42 +/- 0.005 l/kg, respectively. Once the distribution equilibrium was reached between the tissues and plasma, the total body clearance (ClB) and the ratio of the drug present in the peripheral to the central compartment (T/P ratio) were 0.14 +/- 0.002 l/kg/h and 1.73 +/- 0.06, respectively. Based on the pharmacokinetic parameters we obtained, an appropriate intravenous cefpirome dosage regimen for treating cefpiromesensitive bacteria in buffalo calves would be 8.0 mg/kg repeated at 12 h intervals for 5 days, or until persistence of the bacterial infection occurred.
Animals ; Buffaloes/*metabolism/urine ; Cephalosporins/administration & dosage/*pharmacokinetics/*urine ; Injections, Intravenous/veterinary ; Kinetics ; Metabolic Clearance Rate/physiology

BACKGROUND: Type 2 diabetes develops because of defects in both insulin secretion and action. The half-life of insulin in uremia is prolonged because the metabolic clearance rate of insulin in diabetic end stage renal disease (ESRD) patients is reduced with consequence that the dose of insulin and/or oral hypoglycemic agent (OHA) administered in normal renal function make them increase the risk of hypoglycemia. Therefore, we should usually reduce the dose of insulin and/or OHA, or stop administration of insulin and/or OHA if type 2 diabetic patients are progressed to ESRD. But in some patients, that is not true. The aim of this study was to test the hypothesis that insulin resistance plays an important role in (re)evaluation of optimal insulin and/or OHA dose for glycemic control after type 2 diabetic patients are progressed to ESRD. METHODS: Insulin resistance was examined in 23 type 2 diabetic ESRD patients with tight control of glycemia using the K index of the insulin tolerance test (Kitt). We divided 23 patients into three groups. Group 1 (n=10) was defined as patients who were administered neither insulin nor OHA after ESRD. Group 2 (n=9) was defined as patients who were changed from insulin to OHA as drug for glycemic control after ESRD. Group 3 (n=4) was defined as patients in whom insulin or OHA was continuously administered after ESRD without a change of them for glycemic control. We compared the degree of insulin resistance among these three groups. RESULTS: Insulin resistance determined by Kitt was significantly different between group 1 (Kitt, 2.1422/0.94-4.01%/min), group 2 (Kitt, 1.3811/0.79- 3.90%/min) and group 3 (Kitt, 0.8550/0.44-1.81%/min) by using Kruskal-Wallis test (p=0.048). Kitt in group 3 was significantly lower than in group 1 by using Mann-Whitney test (p=0.016). CONCLUSION: Although metabolic clearance of insulin is reduced by renal failure, demand of insulin/ OHA for optimal glycemic control is not reduced in higher insulin-resistant type 2 diabetic ESRD patients on hemodialysis. Insulin resistance plays an important role in determination of optimal insulin/ OHA dose for glycemic control after type 2 diabetic patients are progressed to ESRD.
Half-Life ; Humans ; Hypoglycemia ; Insulin Resistance* ; Insulin* ; Kidney Failure, Chronic* ; Metabolic Clearance Rate ; Renal Dialysis* ; Renal Insufficiency ; Uremia

Morphine is known to inhibit nocturnal uterine contractions in several animal models, and oxytocin is known to be a primary causative factor of uterine contractions. The purpose of the present study was to determine the tocolytic effect of morphine in relation to the pharmacokinetics of oxytocin, after a bolus injection of oxytocin. The metabolism of oxytocin was investigated during the third trimester in baboons. Four animals were placed on a tether system with venous and arterial access, including continuous uterine monitoring. Plasma oxytocin levels were determined by radioimmunoassay after extraction with petroleum ether/acetone. Morphine consistently increased the metabolic clearance rate of oxytocin in all four animals (p < 0.05) and this was in accordance with suppressed uterine contractions. We conclude that morphine could be used as an inhibitor of nocturnal uterine contractions, and that this is caused by the morphine induced increased metabolic clearance rate of oxytocin.
Animal ; Female ; Metabolic Clearance Rate ; Morphine/*pharmacology ; Oxytocin/*pharmacokinetics ; Papio ; Pregnancy ; Tocolytic Agents/*pharmacology ; Uterine Contraction/drug effects

Pharmacokinetic analysis has attracted more and more attentions in the research field of bioactive natural product. However, there is limited study on the pharmacokinetics of polysaccharides. This paper focused on the research progresses of pharmacokinetics of polysaccharide, summarized the applications of chromatography, isotope labeling method, spectrophotometry, fluorospectrophotometry and biological assay in the analysis of polysaccharide pharmacokinetics, elucidated the behaviors of absorption, distribution, degradation and excretion of polysaccharide in experimental animals, and revealed the effects of physicochemical characteristic, administration dose and route on the pharmacokinetic properties of polysaccharide, which could be served as a reference for the related works.
Administration, Oral ; Animals ; Injections ; Intestinal Absorption ; Metabolic Clearance Rate ; Molecular Weight ; Polysaccharides ; administration & dosage ; analysis ; pharmacokinetics ; urine ; Tissue Distribution

Radiotracer techniques were employed to characterize (65)Zn adsorption and desorption in root-cell-wall of hyperaccumulating ecotype (HE) and non-hyperaccumulating ecotype (NHE) species of Sedum alfredii Hance. The results indicated that at the end of a 30 min short time radioisotope loading period, comparable amounts of (65)Zn were accumulated in the roots of the two ecotypes Sedum alfredii, whereas 2.1-fold more (65)Zn remains in NHE root after 45-min desorption. At the end of 60 min uptake period, no difference of (65)Zn accumulation was observed in undesorbed root-cell-wall of Sedum alfredii. However, 3.0-fold more (65)Zn accumulated in desorbed root-cell-wall of NHE. Zn(2+) binding in root-cell-wall preparations of NHE was greater than that in HE under high Zn(2+) concentration. All these results suggested that root-cell-wall of the two ecotypes Sedum alfredii had the same ability to adsorb Zn(2+), whereas the desorption characteristics were different, and with most of (65)Zn binding on root of HE being available for loading into the xylem, as a result, more (65)Zn was translocated to the shoot.
Adsorption ; Biodegradation, Environmental ; Cells, Cultured ; Kinetics ; Metabolic Clearance Rate ; Plant Roots ; cytology ; metabolism ; Sedum ; cytology ; metabolism ; Zinc ; pharmacokinetics