The loading dose

Thus, for drug dosing, one only needs to know the loading dose or the standard dose and the elimination half-life. 

The calculated peak concentration is not always the measured concentration. For bi-exponential kinetics the calculated peak concentration is less, but after oral dosing, the calculated peak concentration is higher than the highest measurable plasma concentration. The peak concentration provides a target for the loading dose to start with (Dload). 

During the time on dialysis (/HD) a fraction (FR) of the amount in the body is eliminated. The required amount in the body often corresponds to the loading dose (Dload) otto (Dload - Dfail). This fraction must be rqftaced by a supplementary dose (Dsuppl) to maintain therapeutic dtug levels for the time interval between two dialysis sessions. 

Begin phenytoin maintenance dose 12 h after the loading dose if indicated... 

The loading dose may be followed by a continuous IV infusion of 20 mg over 24 h. May titrate to a maximum of 40 mg/d if inadequate response. Total duration of therapy not to exceed 4 d... 

Once the loading dose of the AED is administered, it is important to remember to initiate maintenance doses to ensure that therapeutic levels are sustained. Chronic and idiosyncratic side effects as well as potential drug interactions should be considered if the patient will continue AED therapy indefinitely. All drug therapy should be adjusted for any hepatic or renal disease states. Table 28-1 summarizes the drug doses used in SE, and Table 28-2 provides an example of an algorithm for the treatment of patients in SE. Published studies comparing these treatment strategies are summarized in Table 28-3. 

Fosphenytoin Fosphenytoin is a water-soluble, phospho-ester prodrug of phenytoin that is rapidly converted to phenytoin in the body. It is compatible with most IV solutions and is well tolerated as an IM injection, even with the large volumes associated with loading doses (20 to 30 mL).19 It is dosed in phenytoin equivalents (PE), and it can be infused three times as fast as phenytoin, up to 150 mg PE/minute. The loading dose for patients not taking phenytoin is 15 to 20 mg PE/kg. It can be an advantage to use IM fosphenytoin when IV access cannot be obtained immediately and in patients with poor venous access. Although it has fewer cardiovascular side... 

The loading dose of quinidine should be omitted in those patients who have received quinine or mefloquine. 

Corticosteroids are a mainstay in the management of brain I metastases. They reduce edema that typically surrounds sites of metastasis, thereby reducing ICP. A loading dose of dexam-ethasone 10 mg followed by 4 mg by mouth or intravenously every 6 hours typically is used. Symptom relief may occur shortly after the loading dose, although the maximum benefit may not be seen for several days (after definitive therapy). 

For IV administration, the easiest way to determine the loading dose is in terms of Cp and Cmax. For example, if the desired Cmax is 20 pg/mL and a dose of 100 mg gives a Cp of 10 pg/mL, a loading dose of 200 mg should give a Cp of 20 pg/mL, which is the desired Cmax. If this loading dose is followed by maintenance doses of 100 mg every half-life, the plasma concentrations can be maintained at the... 

The maintenance dose needed to replace the amount lost over the dosing interval is the difference between the loading dose and the amount remaining at the end of the interval ... 

The usual loading dose of milrinone is 50 mcg/kg over 10 minutes. If rapid hemodynamic changes are unnecessary, the loading dose should be eliminated because of the risk of hypotension. Most patients are simply started on the maintenance continuous infusion of 0.25 mcg/kg/min (up to 0.75 mcg/kg/min). 

A reduction in the loading dose is recommended for elderly patients, and a larger loading dose is required in obese patients. 

Peak brain concentrations occur 12 to 60 minutes after IV dosing. On average, seizures are controlled within minutes of the loading dose. 

There are no reports of respiratory depression hemodynamic instability is rare, but vital signs should be monitored closely during the loading dose. 

What would be the loading dose of an antibiotic drug with a maintenance dose of 300 mg, half-life of 9 hours and a dosing interval also of 9 hours ... 

In Example 2, if the clinical pharmacist decides to administer 300 mg q8h, what should be the size of the loading dose ... 

In a clinical situation, if it is known that the loading dose is one gram for a drug administered every 12 hours, what should be the maintenance dose The plasma half-life of the drug has been reported to be 4 hours. 

Using a simple one-compartment model, the loading dose and the infusion rate required to maintain a constant plasma concentration can be calculated as follows. 

For example, obesity affects Vi because lipid-soluble drugs diffuse into the adipose tissues of the obese person. Vi is a useful parameter for determining the loading dose for a drug to attain equilibrium after the drug is administered. 

Administer the loading dose in several portions, with roughly half the total given as the first dose. Additional fractions of this planned total dose may be given at 6- to 8-hour intervals, with careful assessment of clinical response before each additional dose. 

Loading 15 mg/kg in 250 mL normal saline infused over 4 hours followed by Maintenance beginning 24 hours after the beginning of the loading dose, 7.5 mg/kg infused over 4 hours, every 8 hours for 7 days or until oral therapy can be instituted. 

Initial loading dose For rapid control of ventricular arrhythmia, give an initial loading dose of 300 mg immediate release (200 mg for patients less than 50 kg [110 lbs]). Therapeutic effects are attained in 30 minutes to 3 hours. If there is no response or no evidence of toxicity within 6 hours of the loading dose, 200 mg every 6 hours may be administered instead of the usual 150 mg. If there is no response within 48 hours, discontinue the drug or carefully monitor subsequent doses of 250 or 300 mg every 6 hours. 

The loading dose for theophylline is based on the principle that each 0.5 mg/kg of theophylline administered as a loading dose will result in a 1 mcg/mL increase in serum theophylline concentration. Defer the loading dose if a serum theophylline concentration can be obtained rapidly. 

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. 

Initially, 1 g of phenytoin capsules is divided into 3 doses (400 mg, 300 mg, 300 mg) and administered at intervals of 2 hours. Normal maintenance dosage is then instituted 24 hours after the loading dose, with frequent serum level determinations. 

To determine maintenance doses administered every 12 hours, reduce the loading dose in proportion to the reduction in the patient s Ccr ... 

Renal function impairment There is no need to adjust single dose therapy for vaginal candidiasis in patients with impaired renal function. In patients with impaired renal function who will receive multiple doses, give an initial loading dose of 50 to 400 mg. After the loading dose, base the daily dose on the following table ... 

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