Metabolism dose-dependent

McKenna, M.J. Zempel, J.A. (1981) The dose-dependent metabolism of CJmethylene chloride following oral administration to rats. Food Cosmet. Toxicol., 19, 73-78... 

Sato A, Nakajima T. 1979a. Dose-dependent metabolic integration between benzene and toluene in vivo and in vitro. Toxicol Appl Pharmacol 48 249-256. 

Jacobs SA, Stoller RG, Chabner BA, and Johns DG. 1977. Dose-dependent metabolism of methotrexate in man and Rhesus monkey. CancerTreat Rep, 61 651 -658. 

Dickinson, R.G. et al., Disposition of valproic acid in the rat Dose-dependent metabolism, distribution, enterohepatic recirculation and choleretic effect, J. Pharmacol. Exp. 

In humans, exposure to paracetamol (acetaminophen) is primarily by the oral route from a wide variety of formulations (tablets, capsules and liquids) either on its own or in combination with other drugs. An estimate of paracetamol (acetaminophen) consumption [prescribed paracetamol (acetaminophen), combination tablets and paracetamol (acetaminophen) without a prescription] was 3500 million 500 mg tablets in the year 2000 The acute toxicity of paracetamol (acetaminophen) in man and experimental animals is due to its dose-dependent metabolic profile. 

Sato, A. and T. Nakajima (1979). Dose-dependent metabolic interaction between benzene and toluene... 

Metabolism of NHEX- C in the rat results in dose dependent formation of C02> with 45% exhaled after a dose of 8 mg/kg NHEX but only 4% after 576 mg/kg (17). Similar results were obtained for NPYR and nitrosoheptamethyleneimine. At doses of 8-12 mg/kg NHEX, 33-37% of the radioactivity was excreted in the urine (17, 52). Urinary metabolites of NHEX were e-caprolactam, e-amino-caproic acid, and 6-aminocaprohydroxamic acid (52). The formation of 6-caprolactam is analogous to results with NPYR and NNN, in which 2-pyrrolidinone and norcotinine were observed as urinary metabolites. Caprolactam did not originate from hexamethylene-imine, a product of denitrosation. 

Oxatomide (l- 3- [4-(diphenylmethyl)-l-piperazinyl] propyl)-l,3-dihydro-2H-benzimidazol-2-one) is an antiallergy drug. Akamatsu has reported that oxatomide decreases neutrophil-generated superoxide anion and hydrogen peroxide formation in a dose-dependent manner. The authors hypothesize that the drug is inhibiting NADPH-dependent oxygen metabolism within the neutrophil (Akamatsu et al., 1993). 

Relatively few human imaging studies have evaluated the effects of marijuana or THC on metabolism or blood flow. Acute intravenous THC in both normal controls and habitual marijuana users led to increased an increased regional cerebral metabolic rate (CMR) in the cerebellum. This increase is positively correlated both with concentrations of THC in the plasma and with the intensity of the subjective sense of intoxication [5]. In a 1997 PET/[lsO]water study with 32 abusers [6], THC dose-depend-ently increased cerebral blood flow (CBF) in the frontal regions, insula... 

Ward et al. [125] investigated the disposition of 14C-radiolabeled primaquine in the isolated perfused rat liver preparation, after the administration of 0.5, 1.5, and 5 mg doses of the drug. The pharmacokinetics of primaquine in the experimental model was dependent on dose size. Increasing the dose from 0.5 to 5 mg produced a significant reduction in clearance from 11.6 to 2.9 mL/min. This decrease was accompanied by a disproportionate increase in the value of the area under the curve from 25.4 to 1128.6 pg/mL, elimination half-life from 33.2 to 413 min, and volume of distribution from 547.7 to 1489 mL. Primaquine exhibited dose dependency in its pattern of metabolism. While the carboxylic acid derivative of primaquine was not detected perfusate after the 0.5 mg dose, it was the principal perfusate metabolite after 5 mg dose. Primaquine was subject to extensive biliary excretion at all doses, the total amount of 14C-radioactivity excreted in the bile decreased from 60 to 30%i as the dose of primaquine was increased from 0.5 to 5 mg. 

In subacute toxicity studies only the highest rifaximin dose (i.e. 100 mg/kg, corresponding to 25 times the therapeutic dose in humans) induced mild toxic effects (like, for instance, acute gastroenteritis) connected to the topical GI action of the drug [59, 255], A dose-dependent increase of the total cholesterol value was recorded in female animals [255], most likely due to an alteration of biliary acid metabolism consequent to the antibiotic effect on gut flora [256]. 

The primary function of the mammalian red blood cell is to maintain aerobic metabolism while the iron atom of the heme molecule is in the ferrous (Fe+2) oxidation state however, copper is necessary for this process to occur (USEPA 1980). Excess copper within the cell oxidizes the ferrous iron to the ferric (Fe+3) state. This molecule, known as methemoglobin, is unable to bind oxygen or carbon dioxide and is not dissociable (Langlois and Calabrese 1992). Simultaneous exposure of sheep to mixtures of cupric acetate, sodium chlorite, and sodium nitrite produced a dose-dependent increase in methemoglobin formation (Calabrese et al. 1992 Langlois and Calabrese 1992). 

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