Drug administration loading dose

For the theophylline example given in Example Maintenance Dose Calculation, the loading dose would be 350 mg (35 L x 10 mg/L) for a 70-kg person. For most drugs, the loading dose can be given as a single dose by the chosen route of administration. 

If an immediate effect is needed, a loading dose (Dload) must be given to administer the therapeutic amount (Dload = Ao). To maintain the drug effect, the maintenance dose (D) must be administered repetitively with the administration interval (Tau). 

Drug Name (Brand Name) Loading Dose Administration Rate Therapeutic Level Side Effects Comments... 

This system is the only osmotic system developed commercially at this time that is suitable for the oral administration of insoluble drugs to humans. It has been utilized in the development of several other drugs including isradipine, doxazosin, diltiazem, contraceptive steroids, glipizide, and verapamil [48-53], The system has also been utilized to codeliver the free bases of compounds normally administered as water-soluble salts such as pseudoephedrine and bromo-pheniramine [54], The latter system includes both a loading dose and a controlled release dose and is intended for applications in the over-the-counter market. 

Administration - The loading dose of aminophylline can be given by very slow IV push or, more conveniently, may be infused in a small guantity (usually 100 to 200 mL) of 5% Dextrose Injection or 0.9% Sodium Chloride Injection. Do not exceed the rate of 25 mg/min. Thereafter, maintenance therapy can be administered by a large volume infusion to deliver the desired amount of drug each hour. Aminophylline is compatible with most commonly used IV solutions. Oral therapy should be substituted for intravenous aminophylline as soon as adeguate improvement is achieved. 

Pyrimethamine is well absorbed after oral administration, with peak plasma levels occurring within 3 to 7 hours. An initial loading dose to saturate nonspecific binding sites is not required, as it is with chloroquine. However, the drug binds to tissues, and therefore, its rate of renal excretion is slow. Pyrimethamine has a half-life of about 4 days. Although the drug does undergo some metabolic alterations, the metabolites formed have not been totally identified. 

Quinine is derived from the bark of the cinchona tree, a traditional remedy for intermittent fevers from South America. The alkaloid quinine was purified from the bark in 1820, and it has been used in the treatment and prevention of malaria since that time. Quinidine, the dextrorotatory stereoisomer of quinine, is at least as effective as parenteral quinine in the treatment of severe falciparum malaria. After oral administration, quinine is rapidly absorbed, reaches peak plasma levels in 1-3 hours, and is widely distributed in body tissues. The use of a loading dose in severe malaria allows the achievement of peak levels within a few hours. The pharmacokinetics of quinine varies among populations. Individuals with malaria develop higher plasma levels of the drug than healthy controls, but toxicity is not increased, apparently because of increased protein binding. The half-life of quinine also is longer in those with severe malaria (18 hours) than in healthy controls (11 hours). Quinidine has a shorter half-life than quinine, mostly as a result of decreased protein binding. Quinine is primarily metabolized in the liver and excreted in the urine. 

FIGURE 2.5 Siimilation of plasma (solid line) and tissue (heavy dashed line) digoxin concentrations after intravenous administration of a 0.75-mg loading dose to a 70-kg patient with normal renal function. Cq is estimated by back extrapolation (dotted line) of elimination-phase plasma concentrations. is calculated by dividing the administered drug dose by this estimate of Cq, as shown. Tissue concentrations are referenced to the apparent distribution volume of a peripheral compartment that represents tissue distribution. (Reproduced with permission from Atkinson AJ Jr, Kushner W. Annu Rev Pharmacol Toxicol 1979 19 105-27.)... 

In 3325 patients who took leflunomide, the rate of drug withdrawal was 42% within 33 months after approval by the US Food and Drugs Administration, and was more likely in patients who received a loading dose. The most common causes of discontinuation were inefficacy (30%), gastrointestinal symptoms (29%), non-adherence to therapy or loss to follow-up (14%), and raised liver enzymes (5%) (50). 

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