Continuous intravenous infusion loading dose

In the previous discussion of the one- and two-compartment models we have loaded the system with a single-dose D at time zero, and subsequently we observed its transient response until a steady state was reached. It has been shown that an analysis of the response in the central plasma compartment allows to estimate the transfer constants of the system. Once the transfer constants have been established, it is possible to study the behaviour of the model with different types of input functions. The case when the input is delivered at a constant rate during a certain time interval is of special importance. It applies when a drug is delivered by continuous intravenous infusion. We assume that an amount Z) of a drug is delivered during the time of infusion x at a constant rate (Fig. 39.10). The first part of the mass balance differential equation for this one-compartment open system, for times t between 0 and x, is given by ... 

B. Continuous intravenous infusion. Administer a loading dose of 5-6 mg/kg IV over 1 hour (not to exceed 50 mg/min children, 1 mg/kg/min), followed by maintenance Infusion of 0.5-3 mg/kg/h titrated to the desired effect. For treatment of status epilepticus, use loading dose of 5-15 mg/kg given by IV infusion over 1 to 2 hours, monitor blood pressure (vasopressor support may be required eg, dopamine) and provide respiratory support, and follow with maintenance Infusion. Electroencephalographic achievement of burst suppression usually occurs with a semm pentobarbital concentration of 25-40 mcg/mL. 

Aminopyrine had been on the market as an antipyretic drug under the name of Pyramidon, but it was withdrawn after toxic side effects were found. Its use required a large loading dose and continuous intravenous infusion to match its clearance, and consequently it could not be used in human subjects. After 1975 tracer doses of [ " Cjaminopyrine were used in human studies, but in the meantime two British physiologists introduced the use of radioactive aniline clearance, which they demonstrated was equal to aminopyrine clearance if suitable analytical methods were used. ... 

Administer caspofungin by slow intravenous (IV) infusion over approximately 1 hour. Candidemia and other Candida infections Administer a single 70 mg loading dose on day 1, followed by 50 mg/day thereafter. The patient s clinical and microbiological response should dictate duration of treatment. In general, continue antifungal therapy for at least 14 days after the last positive culture. 

Intravenous conivaptan had no effects on the electrocardiogram in a randomized, single-blind, placebo- and positive-controlled, parallel-group study, in which an intravenous loading dose of conivaptan of 20 mg was followed by a continuous infusion of 40 or 80 mg/day for 4 days or moxifloxacin 400 mg/day for 4 days (9). 

Aprotinin is not effective after oral administration, but is administered intravenously as a loading dose followed by a continuous infusion. Its activity is expressed as kallikrein inactivation units (KIU). The conventional (Munich) dose regimen consists of an initial 2 x 10 KIU bolus, a similar initial dose to prime the bypass machine, and then 0.5 x 10 KIU/ hour by continuous infusion thereafter. The half-life of aprotinin is about 2 hours. Plasma concentrations of 125 KlU/ml are necessary to inhibit plasmin, but a... 

An example of this approach can be obtained by continuing the theophylline patient case from the section on drug dosing in liver disease. In this example, a 55-year-old, 70-kg man with liver cirrhosis was prescribed a loading dose of theophylline 350 mg intravenously over 20 to 30 minutes, followed by a maintenance dose of 15 mg/h of theophylline as a continuous infusion. The infusion began at 9 A.M., blood samples were obtained at 10 A.M. and 4 P.M., and the clinical laboratory reported the theophylline serum concentrations as 10.9 and 12.3 mg/L, respectively. The patient s theophylline clearance and revised continuous infusion to maintain a Css of 15 mg/L can be computed as follows (patient s Vo estimated at 0.5 L/kg) ... 

The patient is given ZDV intravenously in a 10-hour loading dose of 2 mg per kg of body weight, followed by a continuous infusion of 1 mg per kg of body weight per hour at beginning of labor and until delivery. 

This is best accomplished by giving an intravenous bolus as a loading dose and then titrating the level using a continuous infusion. The rectal administration of aminophylline solution can also rapidly achieve therapeutic blood levels. Asthmatics who are prone to attacks of asthma can successfully utilize this route of administration instead of intravenous therapy. 

Following an intravenous injection of 10 mg propranolol, McAllister (1976) found the values of the elimination rate constant (K) and the apparent volume of distribution (V) to be 0.00505 0.0006min and 295 SSL, respectively (mean SD for six patients). These values were then used to calculate the loading dose (I ) and infusion rate (Q) necessary to instantly obtain and then continuously maintain propranolol plasma concentrations of 12, 40 and 75 ngmL . ... 

In a retrospective analysis of 36 patients who received intravenous levetiracetam for refractory status epilepticus [209 ] a median dose of 3000 mg/day (range 1000-9000) was used as a loading bolus or by continuous pump infusion. Status epilepticus was terminated in 69% of patients. None had cardiac dysrhythmias or significantly reduced blood pressure, or required an increase in the dose of catecholamines. Two patients had nausea and vomiting during levetiracetam loading, leading to aspiration pneumonia in one. 

Observational studies In a retrospective study in 70 patients with bone and joint infections, prolonged, continuous, intravenous clindamycin therapy (600 mg as a loading dose infused over 60 minutes, followed immediately by a continuous infusion of 30-40 mg/kg/day) one patient developed cytolytic hepatitis and one had an allergic rash, both resolved after clindamycin withdrawal [llO ]. 

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