Maximal absorbable dose

Aqueous solubility is typically inversely proportional to lypophilicity. Lypophilicity represents the affinity of a molecule (or moiety) for a lypophilic environment. Dmg solubility is also an important attribute to its oral absorption and subsequent permeability through membranes. In medicinal chemistry, solubility for a 1-mg kg dose of 5,50, and 500 p,g mL is estimated to be low, medium, and high, respectively (Van de Waterbeemd, 2002). Solubility characteristics have long been recognized as important in pharmaceutical chemistry and are part and parcel of the drug design process. For example, the solubility can be used to determine the maximal absorbable dose (MAD), that is. 

A number of mathematical models have been developed to describe the interplay of solubility and these physiological parameters to model dmg absorption. The most simplistic model is the maximal absorbable dose (MAD) calculation. The MAD calculation combines the amount of dmg that can dissolve to form a saturated solution in water equal in volume to the small intestinal volume, with an estimate of the absorption rate and the small intestinal transit time. The maximal absorbable dose is then related to the dose required to achieve the desired therapeutic effect [2], If the estimated MAD is much greater than the predicted dose to achieve a therapeutic effect, this can give confidence enough to take the dmg toward clinical use. Predictions of aqueous solubility may then be useful in predicting the extent of absorption in man. 

The radiopharmaceutical is applied as a single dose maximally of 2 GBq I-lipiodol per session. The estimated tumour-absorbed dose varies widely from a few gray to a few hundred gray (most calculated hy the MIRD - Medical Internal Radiation Dose -method) but at present the correct estimation of this dose remains uncertain. Until now there has been no positive correlation between calculated dose and outcome or tumour reaction. 

A number of factors can limit calcium absorption, and special consideration must be given to calcium dosing to maximize absorption. Large amounts of calcium taken at once cannot be absorbed. Supplement doses should be limited to 500 to 600 mg of elemental calcium per dose. Calcium intake greater than 2500 mg/day should be avoided due to increased risk of toxicity, including hypercalciuria and hypercalcemia. 

Absorption/Distribution - Atomoxetine is well absorbed after oral administration and is minimally affected by food. It is rapidly absorbed after oral administration, with absolute bioavailability of about 63% in extensive metabolizers (EMs) and 94% in poor metabolizers (PMs). Maximal plasma concentrations (Cmax) reached approximately 1 to 2 hours after dosing. At... 

Synthetic levothyroxine sodium is used most commonly and is the drug of choice. Oral doses are incompletely absorbed. In plasma levothyroxine is for more than 99% bound to proteins, mainly to TBG. Maximal effects are reached in 3 weeks and the activity persists for 1-3 weeks after withdrawal of chronic therapy. It has a half-life of 7 days which permits once-daily administration. Its adverse effects mainly consist of signs and symptoms of hyperthyroidism. 

Approximately 50% of an orally administered dose of a-methyldopa is absorbed from the gastrointestinal tract. Both peak plasma drug levels and maximal blood pressure-lowering effects are observed 2 to 6 hours after oral administration. A considerable amount of unchanged a-methyldopa and several conjugated and de-carboxylated metabolites can be found in the urine. 

The carbonic anhydrase inhibitors are well absorbed after oral administration. An increase in urine pH from the HC03 diuresis is apparent within 30 minutes, is maximal at 2 hours, and persists for 12 hours after a single dose. Excretion of the drug is by secretion in the proximal tubule S2 segment. Therefore, dosing must be reduced in renal insufficiency. 

Amiodarone is slowly absorbed with an average bioavailabilty of 50% (range, 22-86%). Food has been shown to increase the rate and extent of absorption. Peak plasma concentrations are seen within 3-7 h (range, 2-12 h) however, the onset of action is not seen for at least 2-3 days and usually not until 1-3 weeks. This delay occurs even if a loading dose is given. Maximal responses may not occur until up to 5 months after starting therapy. Amiodarone is... 

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