Bolus injection volume

Standard Bolus Injection Volumes of Lepirudin According to Body Weight for a 5 mg/mL Concentration ... 

There are limitations and disadvantages to the bolus approach, however. Only a limited volume may be injected, which may prohibit the use of bolus when volumes to be introduced are high (due to, e.g., low active compound solubility or a host of other reasons). Only two devices (syringe and catheter) are available for use in the bolus approach. If a multiple-day course of treatment is desired (say, every day for 15 days), separate injections must be made at discreet entry sites. 

Bolus Injection. The bolus mode consists of the successive perfusions of as many bolus (n) volumes as necessary to reach the cumulative activity required by the scintigraphic examination. A mathematical analysis of this technique results in the following equation ... 

The injected volume corresponding to one bolus is usually quite small, equivalent at the best to the void volume of the column. The principal advantage of the repeated bolus method is that small injection volumes are required. On the other hand, perfused activity measurements using small volumes requires high activity generators. 

Fig. 2.6 S imulated absorption curves for different injection volumes (a) and concentrations (b) of the bolus injection. Note that the reduced initial absorption rate is observed only for large injection volumes and concentrations.

In the clinic a single slow bolus injection of 90 mg of AVI 4126 had a multi-phasic distribution plasma kinetics with half-lives of approximately 1 and 11 hours, but no data were reported on elimination half-life. The volume of distribution was roughly 250ml/kg, somewhat different than those seen in rats. Metabolites were not detected in plasma [25]. 

The following parameters can be calculated from data following a bolus injection into the first accessible pool. Let CL 2 and V[2, respectively/ be the clearance from and volume of the second accessible pool/ and let CL 2/ relf and V 2, relf be the relative clearance from and volume of the second accessible pool. Then... 

Assume a linear, constant-coefficient compartmental model in which compartment 1 is the accessible compartment into which the drug is administered and from which samples are taken. Following a bolus injection of the drug, the volume Vi will be estimated as a parameter of the model. Vi thus will correspond to Va for the noncompartmental model. The clearance rate from compartment 1, CLi, is equal to the product of Vi and A oi ... 

Drugs injected directly into the cerebrospinal fluid have a tendency to produce unpredictable effects, their spread being influenced not only by the volume administered, but also by the concentration of the drug, its specific gravity in relation to that of cerebrospinal fluid, the positioning of the patient (head-up or head-down), and on the speed of injection of bolus doses. Truncal muscle spasms can also increase the spread of drug within the cerebrospinal fluid. All these parameters need to be taken into consideration. Standardization is required as a first step. Rapid bolus injection in particular can produce unexpectedly severe adverse effects. 

FIGURE 3.6 Compartmental analysis for different terms of volume of distribution. (Adapted from Kwon, Y., Handbook of Essential Pharmacokinetics, Pharmacodynamics and Drug Metabolism for Industrial Scientists, Kluwer Academic/Plenum Publishers, New York, 2001. With permission.) (a) Schematic diagram of two-compartment model for compound disposition. Compound is administrated and eliminated from central compartment (compartment 1) and distributes between central compartment and peripheral compartment (compartment 2). Vj and V2 are the apparent volumes of the central and peripheral compartments, respectively. kI0 is the elimination rate constant, and k12 and k21 are the intercompartmental distribution rate constants, (b) Concentration versus time profiles of plasma (—) and peripheral tissue (—) for two-compartmental disposition after IV bolus injection. C0 is the extrapolated concentration at time zero, used for estimation of V, The time of distributional equilibrium is fss. Ydss is a volume distribution value at fss only. Vj, is the volume of distribution value at and after postdistribution equilibrium, which is influenced by relative rates of distribution and elimination, (c) Time-dependent volume of distribution for the corresponding two-compart-mental disposition. Vt is the starting distribution space and has the smallest value. Volume of distribution increases to Vdss at t,s. Volume of distribution further increases with time to Vp at and after postdistribution equilibrium. Vp is influenced by relative rates of distribution and elimination and is not a pure term for volume of distribution. 

Intramuscular or subcutaneous injections are almost always administered a bolus. Typically, the injection volume is less than 1-1.5 mL by the subcutaneous route and usually no more than 2 mL by the intramuscular route, although higher volumes (up to 4 mL) can be administered if essential (Ford 1988). Jorgensen et al. (1996) have shown a correlation between pain and the volume of a subcutaneous injection with volumes of 1-1.5 mL causing significantly more pain than volumes of 0.5 mL or less. Clearly, it is preferable to minimize injection volume wherever possible, particularly if chronic administration is anticipated. When the total volume to be administered cannot be reduced to an acceptable level, two or more injections at multiple sites may be required. 

Fractional elution may be indicated when small volumes of high activity are needed for bolus injection or for labeling. In the case of generator I, it will suffice to elute a total volume of 3 ml, while two 3-ml fractions should be obtained in the case of generator II, since the main activity peak is collected in the second fraction. 

Figure 4.10 demonstrates the limited utility of a scan when the delay is not chosen correctly. Both mathematical and animal models have demonstrated that, when there is reduced cardiac output, intravenous injection will result in a delayed intra-arterial arrival time and a greater peak arterial enhancement [65]. In patients with reduced cardiac output, therefore, once again, a 35- to 40-s prep delay is typically employed. Increasing the degree of arterial opacification can be accomplished simply by utilizing either a larger injection volume or a faster injection rate. With a test bolus, the time density curve generally has a slightly different geometry from that of the main bolus, as shown in Fig. 4.11. This is likely due to injection of a smaller...

Tissue plasminogen activator tPA alteplase (Activase) 59.04 Plasma volume (0.05 Lkg- ) 0.083 (initial) IV bolus injection followed by IV infusion (1.0 in both) Thrombolytic agent used in acute myocardial infarction, acute ischemic stroke and pulmonary embolism... 

Accurate quantitation of the shape and dimensions of all cardiac chambers and myocardium is possible with the Dynamic Spatial Reconstructor (DSR). Generally a single bolus injection of approximately 2ml/kg roentgen contrast agent in the right atrium will provide information of the chamber volumes and myocardial mass within 5% of the actual value. The detailed shape of the chambers and myocardium facilitates evaluation of heart deformed by complex congenital heart disease or myocardial infarction (aneurysm). 

In general, therefore, IV PPIs are likely to be preferred even to infusion of Hz receptor antagonists and bolus injection of Hz receptor antagonists is outdated. A formulation or modification of PPI structure to allow continuous IV infusion of a neutral pH solution so as to bring gastric volume down to close to zero and to elevate pH to 6.0 is also desirable. 

Microbubbles are also ideal tracers because of the small injected volumes and this has been exploited in the liver to identify conditions characterised by arteriovenous shunting such as cirrhosis and metastases an early hepatic vein transit time indicates a haemodynamic abnormality (Blomley et al. 1998). The dynamics of the wash-in and wash-out phases following a bolus injection can be calculated and used to form functional images which are truly quantitative (Eckersley et al. 1998). 

Peak tissue enhancement is determined by blood volume but also depends upon cardiac output (which can vary from one patient to the other) and the volume of CA injected [10]. Furthermore, in the case of all presently available NS-CA, the intra- and extra-vascular components of enhancement cannot be evaluated separately [ 14]. It is also well known that the imaging window in CT angiography is very short and is classically compensated by the injection of high doses of NS-CA or the use of bolus-tracking software. 

Even if a medication is available in multiple formulations and dosage forms, the prescriber must consider the absorption and distribution differences between adult and pediatric patients. Blood supply at injection or infusion site, available blood supply for unit muscle mass, and skeletal muscle mass relative to body mass vary with patient age and size, causing drug absorption to vary, as well. A rapid intravenous bolus in a pediatric patient might result in acute toxicity a slow intravenous infusion, often required in neonates, can cause erratic, unreliable drug delivery in an older child. In addition, the volume of fluid tolerated for intravenous delivery varies significantly with the age and size of the patient. The blood supply and blood flow to and from the injection site are of prime importance since a gradual decrease in blood supply per unit muscle mass is seen with maturation. In addition, the skeletal muscle mass relative to... 

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