Administered dose

Since about 85% of the administered dose is passed unchanged in the feces of the patient, selective toxicity of the dmg can be attributed primarily to poor absorption. Side effects include abdominal pain, nausea, vomiting, diarrhea, loss of appetite, headaches, and vertigo or drowsiness. Skin rashes can also develop. Pyrantel pamoate is produced by Pfi2er, Inc., New York, New York. 

Tocainide is rapidly and well absorbed from the GI tract and undergoes very fitde hepatic first-pass metabolism. Unlike lidocaine which is - 30% bioavailable, tocainide s availability approaches 100% of the administered dose. Eood delays absorption and decreases plasma levels but does not affect bio availability. Less than 10% of the dmg is bound to plasma proteins. Therapeutic plasma concentrations are 3—9 jig/mL. Toxic plasma levels are >10 fig/mL. Peak plasma concentrations are achieved in 0.5—2 h. About 30—40% of tocainide is metabolized in the fiver by deamination and glucuronidation to inactive metabolites. The metabolism is stereoselective and the steady-state plasma concentration of the (3)-(—) enantiomer is about four times that of the (R)-(+) enantiomer. About 50% of the tocainide dose is efirninated by the kidneys unchanged, and the rest is efirninated as metabolites. The elimination half-life of tocainide is about 15 h, and is prolonged in patients with renal disease (1,2,23). 

Where data permit, slope factors listed in IRIS are based on absorbed doses, although to date many of them ha c been based on administered doses. 

Toxicity alucs for carcinogenic effects also can be c.xprcsscd in terms of risk per unit concentration of the substance in the medium where human contact occurs. These measures, called unit risks, are calculated by dividing the slope factor by 70 kg and multiplying by the inhalation rate (20 m /day) or the water consumption rate (2 L/day), respecti ely, for risk associated with unit concentration in air or water. Where an absorption fraction less than 1.0 has been applied in deriving the slope factor, an additional conversion factor is necessary in the calculation of unit risk so that the unit risk will be on an administered dose basis. The standardized duration assumption for unit risks is understood to be continuous lifetime c.xposure. Hence, when there is no absorption conversion required ... 

The daily dose of allopurinol is 300-600 mg. In combination with benzbromarone, the daily allopurinol dose is reduced to 100 mg. In general, allopurinol is well tolerated. The incidence of side effects is 2-3%. Exanthems, pruritus, gastrointestinal problems, and dty mouth have been observed. In rare cases, hair loss, fever, leukopenia, toxic epidermolysis (Lyell syndrome), and hqDatic dysfunction have been reported. Allopurinol inhibits the metabolic inactivation of the cytostatic dtugs azathioprine and 6-mercaptopurine. Accordingly, the administered doses of azathioprine and 6-mercaptopurine must be reduced if allopurinol is given simultaneously. 

In a study of pregnant rats that were exposed to radiolabeled methyl parathion by single dermal application, half-life elimination rate constants for various tissues ranged from 0.04 to 0.07 hour, highest values noted in plasma, kidneys, and fetus. Of the applied radioactivity, 14% was recovered in the urine in the first hour postapplication. By the end of the 96-hour study, 91% of the applied dose had been recovered in the urine. Fecal excretion accounted for only 3% of the administered dose (Abu-Qare et al. 2000). 

Different forms of IFN-a have been available for the treatment of chronic hepatitis B and C, including IFN-a2a and IFN-a2b. The administered dose was 3-5 megaunits three times a week subcutaneously. 

Elevated trichloroethylene levels in expired air were measured in subjects who immersed one hand in an unspecified concentration of trichloroethylene for 30 minutes (Sato and Nakajima 1978). Guinea pigs, exposed to dilute concentrations of aqueous trichloroethylene (-0.020 to 0.110 ppm) over a majority of their body surface area for 70 minutes, excreted 59% of the administered dose in the urine and feces 95% of the metabolized dose was excreted in 8.6 days (Bogen et al. 1992). No other studies were located for humans or animals regarding excretion after dermal exposure to trichloroethylene. 

After exhaustive hydrolysis with bovine liver 3-glucuronidase. Trace -<0.01% administered dose. 

From the mean residence time MRT, the area under the curve AUC and the administered dose D, one can derive the steady-state volume of distribution of... 

Dose may depend on the lapsed time after LMWH administration (e.g., 0.5 mg protamine per 1 mg enoxaparin to a maximum of 50 mg if greater than 8 h has passed since the last administered dose)... 

Opioids maybe administered in a variety of routes including oral (tablet and liquid), sublingual, rectal, transdermal, transmucosal, intravenous, subcutaneous, and intraspinal. While the oral and transdermal routes are most common, the method of administration is based on patient needs (severity of pain) and characteristics (swallowing difficulty and preference). Oral opioids have an onset of effect of 45 minutes, so intravenous or subcutaneous administration maybe preferred if more rapid relief is desired. Intramuscular injections are not recommended because of pain at the injection site and wide fluctuations in drug absorption and peak plasma concentrations achieved. More invasive routes of administration such as PCA and intraspinal (epidural and intrathecal) are primarily used postoperatively, but may also be used in refractory chronic pain situations. PCA delivers a self-administered dose via an infusion pump with a preprogrammed dose, minimum dosing interval, and maximum hourly dose. Morphine, fentanyl, and hydromorphone are commonly administered via PCA pumps by the intravenous route, but less frequently by the subcutaneous or epidural route. 

Oral starting doses of tacrolimus range from 0.1 to 0.2 mg/kg per day in two divided doses. Tacrolimus is available in 0.5, 1, and 5 mg capsules and as an injectable.11 The IV formulation usually is avoided owing to the risk of anaphylaxis because of its castor oil component. Tacrolimus C0 whole-blood levels should be monitored (12 hours after the last administered dose) and maintained between 5 and 15 ng/mL again, desired serum concentrations depend on the transplanted organ, the patient s condition, and the time since transplant.11 A once-daily modified formulation of tacrolimus is being studied currently. 

After completion of induction and restoration of normal hematopoiesis, patients begin intensification (consolidation). The goal of intensification is to administer dose-intensive chemotherapy in an effort to further reduce the burden of... 

A sex difference in the rate of conversion of DIMP to its primary metabolite was observed after intravenous administration of 14C-DIMP in rats (Bucci et al. 1992). The males appeared to convert DIMP to IMPA more actively than the females. The apparent plasma elimination half-life of DIMP was about 45 minutes in males and up to 250 minutes in females. Both the rate and total excretion of the administered dose in urine were also higher in male rats. However, this sex difference was not observed for orally-administered DIMP in minks (Bucci et al. 1992 Weiss et al. 1994). 

The shapes of the profiles for the amount absorbed vs. time for F-PHEA with different MWDs have been reported previously (9). In general, the amount of F-PHEA absorbed increases steadily with time although polymers with smaller MWD are absorbed more rapidly. The effect is illustrated in Table I which is reproduced from a previous paper (9). Interpretation of F-PHEA s absorption kinetics can be complicated however, either by varying the administered dose or the administered molecular weight distribution. Table I shows clearly the increasing percent absorbed of a weight averaged F-PHEA of 4.68 kD as the dose was systematically reduced. This data is evidence of the existence of carrier-mediated transfer for F-PHEA in the... 

During absorption of this particular F-PHEA (Mw = 8.6 kD, Mn = 5.3 kD), through the rat lung, transfer occurred at an apparently constant rate of 110 43 ig/h or 3.5 1% of the administered dose per hour. Because mucociliary clearance from the lower airways occurs very slowly (7) these absorption rates convert to substantial bioavailabilities when the absorption process is extrapolated over a 12 h period [(3.5% x 12) or, around 42% may be feasible]. 

The fraction of the orally administered dose that is bioavailable to the systemic circulation (Fsystemjc) is dependent upon the fraction of the dose that is released from the dosage form (/released), multiplied by the fraction that is absorbed into the portal circulation on its way to the liver (/absorbed this is the fraction that escapes gut metabolism), multiplied by the fraction of the dose that escapes the hepatic first-pass effect (/hepatic)- Since this is a multiplicative process if, for... 

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