Bolus infusion studies

Figure T. Elution time in s to deliver 20 mCi of Kb-82 for bolus infusion studies at a flow rate of 1 mL/s. (Reproduced with permission from Ref. 21. Copyright 1981, J. Nucl. Med.)...

This system will perform both bolus and constant infusion studies with the microprocessor controller. In addition, variable or exponential infusion studies can be performed by using programs residing in a host computer to calculate constants which are sent to the controller through the serial port. 

Figure 9 shows the results of two coronary bypass patients studied with Rb-82 and PET. The uptake of Rb-82 is shown in three 1 cm sections of the myocardium. Each section was imaged with a single bolus infusion of 20 mCi Rb-82. Patient A had blood perfusion defects in the mid and lower sections of the myocardium. 

Clinical studies of the safety and efficacy of Hb-PHP (Apex) as a septicemia therapy are continuing. In a Phase I/II open label, ascending-dose study, patients with volume-refractory, vasopressor-dependent shock secondary to sepsis or presumed sepsis received a bolus infusion of Hb-PHP (25, 50, or lOOmgHb/kg body weight) over 30 min and were observed for cardiovascular changes and adverse effects. Hb infusion was well tolerated and permitted a decrease in vasopressor utilization while maintaining an increasing MAP. No adverse effects on pulmonary, cardiac, renal, or hepatic fimctions have been noted at this dose level Hb-PHP infusion increased SVR and decreased HR. These results supported further study of Hb-PHP in this indication. 

Extravasation of ionic and non-ionic contrast media after rapid bolus infusion has been stndied in 5106 CT studies in adults (276). The mean infusion rate was 2.8 ml/ second and extravasation occurred in 48 patients (0.9%). Injection rate did not correlate with the freqnency or amount of extravasation. Average age and nse of ionic versus non-ionic contrast medium were identical in patients with and without extravasation. There was no sex difference. There was extravasation of ionic contrast medium in 31 patients, nine of whom had extravasation of at least 50 ml. There was extravasation of non-ionic contrast medium in 17 patients, of whom seven had extravasation of at least 50 ml. Hyaluronidase infiltration was often used to treat more extensive extravasation in 10 patients each with extravasation of ionic or non-ionic media. No patient required surgical intervention and none had severe or long-term effects. 

Nievelstein, P.F., Fogelman, A.M., Mottino, G., Frank, J.S. 1991. Lipid accumulation in rabbit aortic intima 2 hours after bolus infusion of low density lipoprotein. A deep-etch and immunolocalization study of ultrarapidly frozen tissue. Arterioscler. Thromb. 11 1795-1805. 

VS. 3 of 13 local bolus infusion animals p < 0.01) and no cures in other study groups. Follow-up study confirmed cisplatin-loaded polymer biocompatibility (36). 

Continuous versus intermittent administration A study randomised 20 patients who underwent a transjugular intrahepatic portosystemic shunt procedure to be treated with either TV bolus infusion of terlipressin (1 mg) followed by continuous infusion (4 mg/24 h) or intravenous bolus injection of ferlipressin (2 mg) followed by intermittent injections (1 mg/6 h) [92 ]. The continuous administration route more stably reduced portal venous pressure and did so with a lower initial IV dose, which could minimise tiie risk of adverse drug reactions. Larger studies are required to assess that possibility. 

Compared to streptokinase, urokinase has been less extensively studied because of its high cost, ie, about 10 times that of a comparable treatment with streptokinase. In addition to the indications described for streptokinase, urokinase is indicated for use in patients with prior streptokinase treatment, or prior Streptococcal infection. Urokinase is commonly used at a loading dose of 4400 units /kg, with a maintenance intravenous infusion dose of 4400 units/kg/h for thromboses other than acute myocardial infarction. In the latter case, a much larger dose, ie, 0.5—2.0 million units/h or a bolus dose of 1.0 million units followed by a 60-min infusion with 1.0 million units, has been found optimal (106). An intracoronary dose of 2000 units/min for two hours was used in one comparative study with intracoronary streptokinase (107). In this study, urokinase exhibited efficacy equivalent to streptokinase with fewer side effects. Other studies with intracoronary urokinase have adrninistered doses ranging from 2,000 to 24,000 units/min with a reperfusion efficacy of 60—89% (108—112). In another urokinase trial, 2.0 million units were adrninistered intravenously, resulting in a thrombolytic efficacy of 60% (113). Effectiveness in terms of reduction in mortaUty rate has not been deterrnined because of the small number of patients studied. 

DOX, as EPI seems to form fewer amounts of ROS and secondary alcohol metabolite, (ii) encapsulation of anthracyclines in uncoated or pegylated liposomes that ensure a good drug delivery to the tumor but not to the heart, (iii) conjugation of anthracyclines with chemical moieties that are selectively recognized by the tumor cells, (iv) coadministration of dexrazoxane, an iron chelator that diminishes the disturbances of iron metabolism and free radical formation in the heart, and (v) administration of anthracyclines by slow infusion rather than 5-10 min bolus (Table 1). Pharmacological interventions with antioxidants have also been considered, but the available clinical studies do not attest to an efficacy of this strategy. 

Kruizinga, W., and Hillen, F. C. (1989b). A comparative study on antitumor effect, cardiotoxicity and nephrotoxicity of doxorubicin administered as bolus, continuous infusion or entrapped in liposomes in the Lou/M Wsl rat, Cancer Chemother. Pharmacol. 24, 341-348. 

The Interventional Management of Stroke (IMS I) Study was a multicenter, open-labeled, single-arm pilot study in which 80 patients (median NIHSS 18) were enrolled to receive IV rt-PA (0.6 mg/kg, 60 mg maximum, 15% of the dose as a bolus with the remainder administered over 30 minutes) within 3 hours of stroke onset (median time to initiation 140 minutes). " Additional rt-PA was subsequently administered via a microcatheter at the site of the thrombus in 62 of the 80 patients, up to a total dose of 22 mg over 2 hours of infusion or until complete recanalization. Primary comparisons were with similar subsets of the placebo and rt-PA-treated subjects from the NINDS rt-PA Stroke Trial. The 3-month mortality in IMS I subjects (16%) was numerically lower but not statistically different than the mortality of the placebo (24%) or rt-PA-treated subjects (21%) in the NINDS rt-PA Stroke Trial. The rate of symptomatic ICH (6.3%) in IMS I subjects was similar to that of the rt-PA-treated subjects (6.6%) but higher than the rate in the... 

The abciximab in Acute Ischemic Stroke trial was a randomized, placebo-controlled dose-escalation study to examine the safety of abciximab in acute stroke. It randomized 74 patients within 24 hours of stroke onset to receive one of four doses of abciximab (by bolus with or without additional infusion, 54 patients) or placebo (20 patients). The median baseline National Institute of Health Stroke Scale (NIHSS) score was 15. The rates of asymptomatic ICH were 19% in the intervention group compared to 5% in the placebo group p = 0.07). Most (9 of 11) of the asymptomatic ICH patients had more severe stroke (NIHSS >14). No cases of symptomatic ICH or major systemic bleeding occurred. There was a trend toward a lower rate of stroke recurrence (2% vs. 5%) and a higher rate of functional recovery at 3 months in the group treated with abciximab than with placebo. 

Heparin may be given intravenously or subcutaneously, and there is no universally accepted dose. Full-dose heparin therapy in adults is a bolus of 5000 units, followed by a continuous infusion of 1000 units/hour. Since the aPTT is already elevated in individuals with DIC, monitoring full-dose heparin therapy may be difficult, and D-dimer and fibrinogen levels maybe better markers of activity. Subcutaneous heparin at a dose of 80 to 100 units/kg every 4 to 6 hours and low-molecular-weight heparins are other, less studied options.25... 

Fluorouracil-based chemotherapy is the standard of care for the adjuvant treatment of colorectal cancer either as a single agent or, more commonly, in combination with other agents. 5-Fluorouracil (5-FU) alone results in a small improvement in survival that can vary based on the method of 5-FU administration. Studies suggest that protracted or continuous intravenous (IV) 5-FU infusion treatment schedules are more effective than bolus therapy.20... 

A comprehensive, randomized, placebo-controlled trial of infused bolus L-arg and its enantiomer (D-arg) included healthy subjects, non-insulin dependent diabetics, hypertensive subjects, and normotensives with primary hypercholesterolemia [147]. A blood-pressure drop and an acute inhibition of ADP-induced aggregation in platelet-rich plasma were observed in all subjects after L-arg administration (<5 g). Both responses to L-arg infusion closely correlated in magnitude, were weaker in noninsulin dependent diabetics and hypercholesterolemics, and declined with increasing age. Notably, D-arg did not elicit any of the L-arg effects, which were reduced by some 70% when superimposed upon ongoing, nonselective NOS inhibition with infused L-N-monomethyl-arginine (L-NMMA). Since D-arg is not a NOS substrate, and L-NMMA is a substrate-competitive NOS inhibitor, the L-arg effects observed in this study were theorized to reflect a rise in vascular NO production by eNOS. In contrast, the inhibition of platelet aggregation observed in vitro after a 5 min L-arg infusion (160 mg total dose) into healthy subjects and patients with angiographic... 

Almost 30 routes exist for administration of drugs to patients, but only a handfbl of these are commonly used in preclinical safety studies (Gad, 1994). The most common deviation from what is to be done in clinical trials is the use of parenteral (injected) routes such as IV (intravenous) and SC (subcutaneous) deliveries. Such injections are loosely characterized as bolus (all at once or over a very short period, such as five minutes) and infusion (over a protracted period of hours, days, or even months). The term continuous infusion implies a steady rate over a protracted period, requiring some form of setup such as an implanted venous catheter or infusion port. 

---