Metabolism parameters

Physiologically Based Phamiacokinetic (PBPK) Model—Comprised of a series of compartments representing organs or tissue groups with realistic weights and blood flows. These models require a variety of physiological information tissue volumes, blood flow rates to tissues, cardiac output, alveolar ventilation rates and, possibly membrane permeabilities. The models also utilize biochemical information such as air/blood partition coefficients, and metabolic parameters. PBPK models are also called biologically based tissue dosimetry models. 

In a third study the time course of the effects of intravenous and intracoronary injections of cysteinyl leukotrienes on metabolic parameters and systemic and coronary hemodynamics was examined in patients with normal coronary arteries [32]. LTD4 (3 nmol, injected into the left coronary artery) induced an early (20 s), transient fall in mean arterial pressure paralleled by rises in heart rate and plasma levels of epinephrine and norepinephrine, all of which had returned to baseline by 10 min. CVR rose at 10 and 15 min and myocardial oxygen extraction at 15 min. Thus, small doses of cysteinyl leukotrienes may induce both an early, transient fall in mean arterial pressure, with secondary sympathoadrenergic activation, and a later increase in small coronary arteriolar resistance. 

Figure 27-2. Relative changes in metabolic parameters during the onset of starvation.

Sato et al. (1991) expanded their earlier PBPK model to account for differences in body weight, body fat content, and sex and applied it to predicting the effect of these factors on trichloroethylene metabolism and excretion. Their model consisted of seven compartments (lung, vessel rich tissue, vessel poor tissue, muscle, fat tissue, gastrointestinal system, and hepatic system) and made various assumptions about the metabolic pathways considered. First-order Michaelis-Menten kinetics were assumed for simplicity, and the first metabolic product was assumed to be chloral hydrate, which was then converted to TCA and trichloroethanol. Further assumptions were that metabolism was limited to the hepatic compartment and that tissue and organ volumes were related to body weight. The metabolic parameters, (the scaling constant for the maximum rate of metabolism) and (the Michaelis constant), were those determined for trichloroethylene in a study by Koizumi (1989) and are presented in Table 2-3. 

Recent reports on biosorbents based on diverse types of macrophytes are found widely in the literature. Free-floating aquatic plants from the genera Salvinia, Azolla, Eichhornia, Lemna, and Pistia have been described the most. S. natans biomass was able to uptake As(V) at low initial concentrations from 0.25 to 2 mg/L (74.8% and 54%, respectively). The experimental data fitted well to both Langmuir and Freundlich isotherms. The effect of pH and biomass quantities on sorption rate has also been investigated along with some metabolic parameters.105... 

Organ clearances are usually based on in vivo rather than in vitro studies. Drug metabolic parameters, Vm and Km, can be estimated from in vitro hepatic enzyme and hepatocyte preparations [53], Knowledge of total clearance and fractional... 

In addition to the mechanistic simulation of absorptive and secretive saturable carrier-mediated transport, we have developed a model of saturable metabolism for the gut and liver that simulates nonlinear responses in drug bioavailability and pharmacokinetics [19]. Hepatic extraction is modeled using a modified venous equilibrium model that is applicable under transient and nonlinear conditions. For drugs undergoing gut metabolism by the same enzymes responsible for liver metabolism (e.g., CYPs 3A4 and 2D6), gut metabolism kinetic parameters are scaled from liver metabolism parameters by scaling Vmax by the ratios of the amounts of metabolizing enzymes in each of the intestinal enterocyte compart-... 

Spears, J.W., E.E. Hatfield, and R.M. Forbes. 1979. Nickel for ruminants II. Influence of dietary nickel on performance and metabolic parameters. Jour. Anim. Sci. 48 649-657. 

Wittenberg, K.M. and T.J. Devlin. 1987. Effects of dietary molybdenum on productivity and metabolic parameters of lactating beef cows and their offspring. Canad. Jour. Anim. Sci. 67 1055-1066. 

Metabolic Effects. In studies where metabolic parameters (blood pH, electrolytes, glucose) were measured, no effects were seen after inhalation exposure to -hexane in Fischer 344 rats at up to... 

Metabolic Effects. Metabolic effects have not been reported in humans after exposure to -hexane. In animal studies where metabolic parameters (blood pH, electrolytes, glucose) were measured, no effects were seen after inhalation exposure to -hexane in rats at up to 10,000 ppm for 6 hours a day, 5 days a week for 13 weeks (Cavender et al. 1984) or in B6C3Fj mice similarly exposed (Dunnick et al. 1989 ... 

Ploemen, J.H.T.M., L.W. Wormhoudt, G.R.M.M. Haenen, et al. 1997. The use of human in vitro metabolic parameters to explore the risk of hazardous compounds the case of ethylene dibromide. Toxicol. Appl. 

The cephalosporin nucleus is synthesized with a beta-lactam ring attached to a six-membered dihydrothiazine ring. Unlike the penicillin nucleus, the cephalosporin nucleus is much more resistant to beta-lactamase. Moreover, it has large areas for possible modifications. Modifications Rj in the acyl side chain alter the antibacterial activity, while modifications of R2 are associated with changes in the pharmacokinetics and metabolic parameters of the drug. 

Monitoring Carefully monitor standard hypercalcemia-related metabolic parameters, such as serum levels of calcium, phosphate, magnesium, and potassium following pamidronate and zoledronic acid initiation. Also, closely monitor electrolytes, creatinine as well as CBC, differential and hematocrit/hemoglobin. Carefully monitor patients who have preexisting anemia, leukopenia or thrombocytopenia in the first 2 weeks following treatment. 

Cyprotex, using Cloe Screen , evaluates pharmacokinetic properties in vitro and establishes a broad portfolio of in vitro assays that allows researchers to investigate the metabolism parameters for drug discovery and development. This company supplies the following data and assays (276) microsomal stability,... 

Internal burdens of epoxybutene in humans resulting from exposure to butadiene were predicted from models by Kohn and Melnick (1993), Johanson and Filser (1996) and Csanady et al. (1996) and were compared with simulations for rats and mice. In the model of Kohn and Melnick (1993), metabolic parameters were incorporated which had been obtained by Csanady et al. (1992) by measuring butadiene and epoxybutene oxidation and epoxybutene hydrolysis in human liver and lung microsomes in vitro, and conjugation of epoxybutene with glutathione in human liver and lung cytosol. Tissue blood partition coefficients were theoretically derived. The body burden of epoxy butene following exposure to 100 ppm butadiene for 6 h was predicted to be 0.056 pmol/kg in humans. 

A physiologically based pharmacokinetic model for predicting ethylene dibromide kinetics and consequent toxicity, based on in-vitro metabolic parameters of rodents and humans and on the use of scaling factors, has been presented (Ploemen et al., 1997). Its most important prediction is that the GST pathway is significantly active even at low ethylene dibromide concentrations, which has important implications for risk assessment. 

Continuous subcutaneous insulin infusion has been compared with short-acting insulins plus glargine or isophane as long-acting insulins for 1 year in 32 patients with poor control (252). Four of them had serious attacks of hypoglycemia. There were no differences in HbAic or other metabolic parameters (including lipids). In those treated with continuous subcutaneous insulin infusion, the reduction in the amount of insulin required was larger. 

Bowen, J., Noakes, M., and Clifton, P. M. (2005). Effect of calcium and dairy foods in high protein, energy-restricted diets on weight loss and metabolic parameters in overweight adults. Inf. ]. Obes. (Land.) 29, 957-965. 

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