Dose ranges

Doses range from 6 to 33 ppm ia the diet, but very htde if any ionophore can be measured ia the circulation after feeding. Monensia is absorbed from the gut, metabolized by the Hver, and excreted iato the bile and back iato the gut. Thus tissue and blood concentrations are very low. Over 20 metabohtes of monensia, which have Htde or ao biological activity, have beea ideatified (47,55). 

Absorption of mannitol (209), sorbitol (210), and xyfltol (4) from the intestinal tract is relatively slow, compared to that of glucose. In humans, approximately 65% of orally adrninistered mannitol is absorbed in the dose range of 40—100 g. About one-third of the absorbed mannitol is excreted in the urine. The remainder is oxidized to carbon dioxide (211). 

The LD q is calculated from data obtained by using small groups of animals and usually for only a few dose levels. Therefore, there is an uncertainty factor associated with the calculation. This can be defined by determining the 95% confidence limits for the particular levels of mortaUty of interest (Fig. 7). The 95% confidence limits give the dose range for which there is only a 5% chance that the LD q will be outside. 

Up to 80% of oral doses of ascorbic acid are absorbed in humans with intakes of less than 0.2 g of vitamin C. Absorption of pharmacological doses ranging from 0.2 g to 12 g results in an inverse relationship, with less than 20% absorption at the higher doses. A single oral dose of 3 g has been reported to approach the absorptive capacity (tissue saturation) of the human intestine. Higher blood levels can be attained by providing multiple divided vitamin C doses per day. 

Compared to streptokinase, urokinase has been less extensively studied because of its high cost, ie, about 10 times that of a comparable treatment with streptokinase. In addition to the indications described for streptokinase, urokinase is indicated for use in patients with prior streptokinase treatment, or prior Streptococcal infection. Urokinase is commonly used at a loading dose of 4400 units /kg, with a maintenance intravenous infusion dose of 4400 units/kg/h for thromboses other than acute myocardial infarction. In the latter case, a much larger dose, ie, 0.5—2.0 million units/h or a bolus dose of 1.0 million units followed by a 60-min infusion with 1.0 million units, has been found optimal (106). An intracoronary dose of 2000 units/min for two hours was used in one comparative study with intracoronary streptokinase (107). In this study, urokinase exhibited efficacy equivalent to streptokinase with fewer side effects. Other studies with intracoronary urokinase have adrninistered doses ranging from 2,000 to 24,000 units/min with a reperfusion efficacy of 60—89% (108—112). In another urokinase trial, 2.0 million units were adrninistered intravenously, resulting in a thrombolytic efficacy of 60% (113). Effectiveness in terms of reduction in mortaUty rate has not been deterrnined because of the small number of patients studied. 

Some of the adverse reactions seen with antineoplastic dragp are listed in the Summary Drug Table Antineoplastic Dru i. Appropriate references should be consulted when administering these dragp because there are a variety of uses, dose ranges, and, in some instances, many adverse reactions. 

Pharmacokinetics concerns the fate of a dmg in the body at the approximate therapeutic dose range, while toxicokinetics assesses behaviour at the higher dose levels associated with toxic effects. The fate of a dmg is dictated by the rates of ... 

Purpose Explore Therapeutic Efficacy (dose ranging and dose-response curves, pharmacodynamics,... 

Compound Animals Route of administration Number of doses Range of doses [mg/kg]... 

Anton RF, Pettinati H, Zweben A, et al A multi-site dose ranging study of nalmefene in the treatment of alcohol dependence. J Clin Psychopharmacol 24 421 28, 2004 Aragon CM, Stotland LM, Amit Z Studies on ethanol-brain catalase interaction evidence for central ethanol oxidation. Alcohol Clin Exp Res 15 165-169, 1991 Arizzi MN, Correa M, Betz AJ, et al Behavioral effects of intraventricular injections of low doses of ethanol, acetaldehyde, and acetate in rats studies with low and high rate operant schedules. Behav Brain Res 147 203—210, 2003 Azrin NH, Sisson RW, Meyers R, et al Alcoholism treatment by disulfiram and community reinforcement therapy. J Behav Ther Exp Psychiatry 13 105—112, 1982 Babor TF, Kranzler HR, Lauerman RL Social drinking as a health and psychosocial risk factor Anstie s limit revisited, in Recent Developments in Alcoholism, Vol 5. Edited by Galanter M. New York, Plenum, 1987, pp 373 02... 

Anton RF, Pettinati H, Zwehen A, et al A multi-site dose ranging smdy of nalmefene in the treatment of alcohol dependence. J Clin Psychopharmacol 24 421 28, 2004 Azrin NH Improvements in the community reinforcement approach to alcoholism. Behav Res Ther 14 339-348, 1976... 

Pharmacokinetic studies demonstrated good oral bioavailability of maraviroc and a terminal half-life of 16-23 h following multiple dosing (Abel et al. 2003 Walker et al. 2005). Single doses of up to 900 mg and multiple doses of up to 300 mg BID for 28 days were well tolerated (Abel et al. 2003 Russell et al. 2003 Walker et al. 2005). In Phase 2a studies, treatment-naive HIV-1 patients with R5 virus who received maraviroc monotherapy at doses ranging from 25 mg QD to 300 mg BID for 10 days experienced a median viral load reduction of 1.64 log jg copies/mL and... 

The most important potential complication of phenol-based peels is cardiotoxicity. Phenol is directly toxic to myocardium. Studies in rats have shown a decrease in myocardial contraction and in electrical activity following systemic exposure to phenol [i6]. Since fatal doses ranged widely in these studies, it seems that individual sensitivity of myocardium to this chemical exists. In humans neither sex/age nor previous cardiac history/blood phenol levels are accurate predictors for cardiac arrhythmia susceptibility [17]. 

The drug has a broad dose range but efficacy in most instances may not be apparent until doses of 400 mg have been reached. An unusually large number of participants drop out because of lack of drug efficacy in some of the major trials (Arvanitis and Miller, 1997). 

Qureshi Al, Harris-Lane P, Kirmani IF, Janjua N, Divani AA, Mohammad YM, Suarez Jl, Montgomery MO. Intra-arterial reteplase and intravenous abciximab in patients with acute ischemic stroke an open-label, dose-ranging, phase I study. Neurosurgery 2006 59 789-796 [discussion 796-787]. 

C Low dose effects usually not measurable directly In human or animal observations Need to extrapolate observed high dose effects to low or zero dose range by theoretical dose-response models ... 

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