Intravenous bolus dose

FIGURE 1. Change in the apparent volume of distribution of PCP as a function of time following administration of an intravenous bolus dose of 3H-PCP (6.4 pg) in a male dog (19.5 kg)... 

A 36-year-old male is seen in the ED with tachycardia, a respiratory rate of 26 breaths per minute (BPM), and EKG evidence of an arrhythmia. An intravenous bolus dose of an antiarrhythmic agent is administered, and within 30 s, he has a respiratory rate of 43 BPM and complains of a burning sensation in his chest. 

The plasma concentration of a drug immediately following a 50-mg intravenous bolus dose of the drug was found to be 0.84 mcg/mL. What is the apparent volume of distribution of the drug ... 

Intravenous bolus dose of a 500-mg dose of an antibiotic every six hours in a patient produces minimum steady-state concentration of 10 meg/ mL. If the desired minimum steady-state concentration in this patient is 16 mcg/mL, calculate the size of dose needed to change this concentration. Assume that the drug follows linear kinetics. 

Intravenous bolus dose in a rat efficacy model measuring potency, duration of action, and plasma levels for effect... 

The human intravenous bolus dose of oximes in nerve agent treatment ranges between 250 and 500 mg ". Side effects of oxime treatment in humans were monitored in 750 volunteers, and the main adverse effects reported were changes in blood pressure, pulse rate, dizziness, nausea and blurred vision . Oral administration of oximes produces gastrointestinal distress. ... 

Theoretical depiction of plasma concentrations following either an intravenous bolus dose immediately followed by initiation of a continuous intravenous infusion or initiation of a continuous intravenous infusion only. 

Route of administration Integrilin is administered intravenously by constant rate infusion, preceded by an intravenous bolus dose. 

Recommended dosage and monitoring requirements In AMI, reperfusion has been achieved with single intravenous bolus doses of TNKase 30 to 50 mg, based on body weight. The dose of TNKase should not exceed 50 mg. Concomitant aspirin and heparin have usually been given. 

Sedation during unpleasant endoscopic, radiological, and other procedures—intravenous bolus doses. 

Linear pharmacokinetics. For a simple linear pharmacokinetics case, the body can be modeled as a single drug compartment with first-order kinetic elimination—where the dose is administered and drug concentrations are drawn from the same compartment. For an intravenous bolus dose, the expected drug plasma concentration Cp versus time curves are shown in Fig. 1.10. The kinetics for this system are described by Eq. (1.6). The well-known solution to this equation is given by Eq. (1.7), and a linearized version of this solution is given in Eq. (1.8) and shown graphically in Fig. 1.13. 

Instantaneous input (IB). Truly instantaneous input (IB) does not physically exist in fact, the kinetic order is mathematically undefined. However, when the input kinetics are exceedingly fast compared with distribution and elimination kinetics, the dose provides a relatively instantaneous input. The best example of an instantaneous input is an intravenous bolus dose—where the drug is administered over a short period (<5 minutes) and directly into the systemic circulation. Figure 1.5 (left panel) shows this type of input being given at time = t. When the intravenous bolus is given repetitively at a fixed interval... 

If we know input(f) and Cp(t), we can extract disposition ). The easiest way to accomplish this deconvolution (extraction) is to give an intravenous bolus dose and measure Cp(t), which will exactly mirror the underlying disposition ). Once disposition ) is known (and assumed not to change for the same drug), Cp(t) can be predicted for any input(t), or... 

If drug had been administered in equally sized multiple intravenous bolus doses at equally spaced t time intervals (e.g., t = 6 h), then an accounting of accumulated drug between doses must be instituted. Figure 1.18, similar to the zero-order input, shows that repetitive instantaneous dosing will produce an average Cp profile similar to Fig. 1.17. 

For multiple intravenous bolus doses, Cp in the nth dosing period is... 

Intravenous bolus doses of 1 mg/kg produce transient facial flushing and, rarely, dyspnea. Adrenocorticotropin (Corticotropin, ACTH, ACTH, 24)... 

Figure 1 Plasma concentration time profiles for a single 42-mg dose of a hypothetical drug with a half-life of 8 hours, Vj 42 liters, and oral bioavailability of 80%. Dashed curve intravenous bolus dose. Solid curve oral dose. Dotted horizontal lines represent plasma concentrations required for efficacy (green) and for the onset of adverse events (red).

If interest focuses entirely on the estimation of population parameters, then the simplest approach is to combine all the data as if they came from a single individual (1). The doses may need to be normalized so that the data are comparable. Equation 10.6 would be applicable if an intravenous bolus dose were administered. The minimization procedure is similar to that described in Figure 10.1. 

The pressor response to big ET-1 can be used as the basis for an in vivo test for ECE inhibitors. In the pithed rat, an intravenous bolus dose (1 nmol/kg) of big ET-1, produces a marked and sustained rise in arterial pressure Figure 8.4) which can be inhibited in a dose-related manner by 1 minute pre-treatment with a bolus dose of phosphoramidon, 1-10 mg/kg i.v. Figure 8.5). 

A 52-year-old woman with a wide-complex tachycardia was given adenosine 6,12, and another 12 mg as intravenous bolus doses immediately after the third dose she developed ventricular fibrillation (27). She recovered with cardioversion. 

All were successfully treated with hyperinsulinemia/ euglycemia therapy. The authors described the mechanism of action of this form of therapy, which is mainly related to improvement in cardiac contractility and peripheral vascular resistance and reversal of acidosis. They proposed indications and dosing for this therapy consisting in most cases of intravenous glucose with an intravenous bolus dose of insulin 1 U/kg followed by an infusion of 0.5-1 U/kg/hour until the systolic blood pressure is over 100 mm/Hg and the heart rate over 50/minute. Hyperinsulinemia/euglycemia therapy is currently reserved as an adjunct to conventional therapy and is recommended only after an inadequate response to fluid resuscitation, high-dose calcium salts, and pressor agents. 

Only six of 36 children who took overdoses of co-phenotrope had signs of atropine overdose (central nervous system excitement, hypertension, fever, flushed dry skin) (1). Opioid overdose (central nervous system and respiratory depression with miosis) predominated or occurred without any signs of atropine toxicity in 33 cases (92%). Diphenoxylate-induced hjrpoxia was the major problem and was associated with slow or fast respiration, hypotonia or rigidity, cardiac arrest, and in three cases cerebral edema and death. Respiratory depression recurred 13-24 hours after the ingestion in seven cases and was probably due to accumulation of difenoxine, an active metabolite of diphenoxylate. Recommended treatment is an intravenous bolus dose of naloxone, followed by a continuous intravenous infusion, prompt gastric lavage, repeated administration of activated charcoal, and close monitoring for 24 hours. 

Cerebral blood flow velocity in infants treated with an intravenous bolus dose of aminophylUne was reduced, perhaps because of a reduction in PCO2, due to aminophylUne (33). 

When the drug is administered as an intravenous bolus dose, the total areas under the curves can be calculated from the coefficients and exponents of the equation describing the disposition curve and obtained by compartmental pharmacokinetic analysis of the plasma concentration-time data. 

Regardless of whether the data are analysed by a compartmental or non-compartmental method, the duration of blood sampling and the limit of quantification of the analytical method used to measure the drug concentration are important features of the pharmacokinetic study. The MRT, after an intravenous bolus dose of a drug can be estimated from either plasma drug concentration or urinary excretion data (Rowland Tozer, 1989). 

The model was run with a single intravenous bolus dose of 1 mg/kg at various times during a 22-day rat gestation period and compared with previously published (different author) maternal and fetal organ concentrations. The model was also run with a daily dosing for 98 days, ending on Gd 20, to simulate a typical human dietary exposure pattern for a frequent consumer of methylmercury-contaminated food. 

For simplicity, the intravenous bolus one-compartment model is used for illustrative purposes. After introduction of an intravenous bolus dose (Dq) into the single compartment, the drug is assumed to distribute instantaneously through all fluids and tissues of the body. The property of kinetic homogeneity is also assumed. 

The plasma kinetics of the analgesic were describable by the following expression after the intravenous bolus dose, with Co = 45.0 and K = 0.50 h 1 ... 

Figure 8.6 Observed PCA time course following the administration of an intravenous bolus dose of warfarin...

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