Intravenous infusion, drug concentration with

The same relationship to k i and half-life also apply, so that as with intravenous infusion 87.5 % of the final steady state concentration is achieved following administration of the drug for three half-lives. 

True steady state is usually only achieved for a prolonged period with intravenous infusion. If we assume that we wish for a similar steady value after oral administration, then we need to balance our dosing frequency with the rate of decline of drug concentration and the rule of thumb referred to earlier (dosing interval equal to drug half-life) can be applied. Unbound clearance and free drug are particularly applicable to drugs delivered by the oral route. For a well-absorbed compound the free plasma concentrations directly relate to Cli (intrinsic unbound clearance). 

By setting the input function, I(t), in the differential equations on p. 28 to a constant rather than zero the equations can be solved to yield the disposition function for an intravenous infusion. With a fixed rate infusion, the plasma concentration will gradually increase towards a steady state concentration, CSS. Since CSS is constant, the amount of drug entering the body via the infusion at steady state must equal that being eliminated, (i.e. the clearance). Thus the infusion rate, R, e.g. mg min-1, needed to reach CSS is R=CSS.CI. It will take approximately 4 to 5 terminal half-lives to reach 95% CSS. Note that if the infusion rate is doubled CSS will also double, but the time taken to reach CSS remains the same, i.e. it is independent of the infusion rate (Figure 2.6). 

The highly polar ionic character of EDTA limits its oral absorption. Moreover, oral administration may increase lead absorption from the gut. Consequently, EDTA should be administered by intravenous infusion. In patients with normal renal function, EDTA is rapidly excreted by glomerular filtration, with 50% of an injected dose appearing in the urine within 1 hour. EDTA mobilizes lead from soft tissues, causing a marked increase in urinary lead excretion and a corresponding decline in blood lead concentration. In patients with renal insufficiency, excretion of the drug—and its metal-mobilizing effects—may be delayed. 

Figure 8.4 The variation of the concentration of a drug in the plasma (Cp) with time when administered by (a) a rapid single intravenous injection and (b) intravenous infusion. With rapid intravenous injections the graph does not show the time taken to carry out the injection it is normally taken as being spontaneous. In these cases the curve starts at the point where the first plasma concentration measurements were taken...

A patient is being treated with morphine by intravenous infusion. The steady state plasma concentration of the drug is to be maintained at 0.04 fig cm 3. Calculate the rate of infusion necessary assuming a first order elimination process (for morphine Vd is 4.0 dm3 and tU2 is 2.5 hours). 

The concentrated form of metronidazole hydrochloride reacts with aluminium needles used for drug administration. Metronidazole hydrochloride should not be mixed with other drugs, including antibiotics, during intravenous infusions.15... 

With continuous intravenous infusion, the rate of drug entry into the body is constant. In the majority of cases, the elimination of a drug is first-order, that is, a constant fraction of the agent is cleared per unit time. Therefore, the rate of drug exit from the body increases proportionately as the plasma concentration increases and at every point in time is proportional to the plasma concentration of the drug. 

The flow of pancreatic juice and bile was tested before and after the experiment by means of an intravenous bolus of 5 pmol/kg secretin. Before the experiment the duodenum was continuously perfused at a rate of 2 ml/min for 435 min with isotonic saline containing phenol red (10 mg/1) as a marker. After drug treatment (intravenous infusion of gastrin-releasing peptide or duodenal HC1 perfusion) pancreatic and hepatic secretions were collected in 15-min periods and the volumes determined by weighing. Duodenal effluents were collected in 15-min periods and phenol red concentrations determined spectrophotometrically. Blood sampled were withdrawn for determination of secretin by radioimmunoassay. 

Note Because it takes so long for an infusion to provide stable therapeutic drug concentrations, lidocaine therapy of life-threatening cardiac arrhythmias is usually begun by administering an intravenous loading dose together with an infusion. 

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