Intravenous bolus injection

Adenosine is produced by many tissues, mainly as a byproduct of ATP breakdown. It is released from neurons, glia and other cells, possibly through the operation of the membrane transport system. Its rate of production varies with the functional state of the tissue and it may play a role as an autocrine or paracrine mediator (e.g. controlling blood flow). The uptake of adenosine is blocked by dipyridamole, which has vasodilatory effects. The effects of adenosine are mediated by a group of G protein-coupled receptors (the Gi/o-coupled Ai- and A3 receptors, and the Gs-coupled A2a-/A2B receptors). Ai receptors can mediate vasoconstriction, block of cardiac atrioventricular conduction and reduction of force of contraction, bronchoconstriction, and inhibition of neurotransmitter release. A2 receptors mediate vasodilatation and are involved in the stimulation of nociceptive afferent neurons. A3 receptors mediate the release of mediators from mast cells. Methylxanthines (e.g. caffeine) function as antagonists of Ai and A2 receptors. Adenosine itself is used to terminate supraventricular tachycardia by intravenous bolus injection. 

The plasma half-life of 6-MP after intravenous bolus injection is 21 min in children and is twofold greater in adults. After oral intake peak levels are attained within 2 h. 6-MP is used for the treatment of ALL and has shown certain activity in chronic myelogenous leukemia. The major side effects involve myelosuppression, nausea, vomiting, and hepatic injury. 

One compound from this series, (10), has been tested in vitro in human myometrium tissue obtained at term following caesarean section and shown to inhibit contractions induced by oxytocin [44] with a pA2 of 7.6. This is one of the first direct indications that the use of an oxytocin antagonist may be of benefit in the treatment of preterm labour in humans. This compound has been extensively studied in the near-term baboon and has been shown to inhibit nocturnal and near-term contractions following an intravenous bolus injection [45]. Further studies on the effect of oxytocin antagonism in the weeks leading up to delivery in the baboon have also been published [46]. 

In vivo Release of Desmopressin and Somatostatin. The in vivo release of Desmopressin and Somatostatin after subcutaneous and intramuscular injections of the peptide in the cubic or the lamellar phase has been studied in the rabbit. Blood was sampled at regular intervals, and systemically absorbed Desmopressin and Somatostatin were determined as the specific immunoreactitvity in plasma of the actual peptide. For details of the analyses with dDAVP, consult ref. 9. For comparison, Desmopressin-like and Somatostatin-like immunoreactitvity (dDAVP-LI and SRIF-LI) in plasma after intravenous bolus injections of the two peptides were determined as well. 

Fig. 22 (A) Plasma concentration of SMA-NCS and NCS in human after an intravenous bolus injection. (B) Intratumor concentration of SMA-NCS, NCS, and mitomycin (MMC). SMA-NCS exhibits a much higher and more prolonged tumor concentration than MMC and NCS. All drugs were given as an intravenous bolus at 10 mg/kg to rabbits bearing VX-2 tumor in...

LD50 acute toxicity assessed in CDl male mice after a single intravenous bolus injection. Values are calculated from the number of mice surviving the injection. 

Animal experiments have shown (A3) that equilibration of lignocaine between blood and brain occurs relatively slowly. This may explain why plasma levels of lignocaine that can readily be tolerated, without cerebral side effects, after intravenous bolus injection nevertheless are associated with serious toxic symptoms when produced by constant intravenous infusion or when resulting from impaired metabolic degradation. 

The plasma half-fife of an intravenous bolus injection of mercaptopurine is 21 minutes in children and 47 minutes in adults. After oral administration, peak plasma levels are attained within 2 hours. The drug is 20% bound to plasma proteins and does not enter the CSF. Xanthine oxidase is the primary enzyme involved in the metabolic inactivation of mercaptopurine. 

Cytarabine is rapidly metabolized in the liver, kidney, intestinal mucosa, and red blood cells and has a half-life in plasma of only 10 minutes after intravenous bolus injection. The major metabolite, uracil arabinoside (ara-U), can be detected in the blood shortly after cytarabine administration. About 80% of a given dose is excreted in the urine within 24 hours, with less than 10% appearing as cytarabine the remainder is ara-U. When the drug is given by continuous infusion, cytarabine levels in CSF approach 40% of those in plasma. 

The elimination half-life of lignocaine following an intravenous bolus injection is 1.5 to 2.0 hours. 

They produces headache, dizziness, dry mouth, rashes. CNS effects include restlessness, delirium, hallucinations, convulsion and coma. Intravenous bolus injection cause bradycardia, arrhythmia and... 

This is primarily an anticonvulsant. Because of a wide range of toxic side effects its use as an antiarrythmic is limited to the treatment of arrhythmias caused by digitalis toxicity. Intravenous bolus injections can cause myocardial depression, hypotension, AV block and bradycardia. 

Effects of an -selective (phenylephrine), 13-selective (isoproterenol), and nonselective (epinephrine) sympathomimetic, given as an intravenous bolus injection to a dog. Reflexes are blunted but not eliminated in this anesthetized animal. BP, blood pressure HR, heart rate. 

Hering, W. Schlecht, R., Geisslinger, G, Biburger, G, Dinkel, M., Brune, K., and Ruegheimer, E. (1995) EEG analysis and pharmacodynamic modelling after intravenous bolus injection of eltanolone (pregnanoloneJEur. J. Anaesthesiol., 12 407—415. 

Choline esters are poorly absorbed and poorly distributed into the central nervous system because they are hydrophilic. Although all are hydrolyzed in the gastrointestinal tract (and less active by the oral route), they differ markedly in their susceptibility to hydrolysis by cholinesterase in the body. Acetylcholine is very rapidly hydrolyzed (see Chapter 6 Introduction to Autonomic Pharmacology) large amounts must be infused intravenously to achieve concentrations high enough to produce detectable effects. A large intravenous bolus injection has a brief effect, typically... 

A. Korfel, I.M. von Broen,Y. Bankmann, and D.K. Hossfeld. 1996. Phase I clinical and pharmacokinetic study of LU103793 (cemadotin hydrochloride) as an intravenous bolus injection in patients with metastatic solid tumors. Onkologie 19 490-495. 

PMOs have been evaluated for adverse effects after intravenous bolus injections in both primates (GLP studies by Sierra Biomedical) and man (GCP studies at MDS Harris). No alterations in heart rate, blood pressure, or cardiac output were observed. In summary, bolus injections of PMO by local catheter-based delivery devices are feasible. 

The model was used to identify indocyanine green profile in man after qo = 10 mg intravenous bolus injection. Both injection and sampling sites (zq and z, respectively) were closely located on the ring-shaped tube. The model of drug administration was a thin Gaussian function ... 

The test substance is then administered by intravenous bolus injection or continuous infusion, or by intraduodenal application. CFRs are registered for 2 to 4 times over 60 min and compared to pre-treatment values. 

Blood collection from the femoral artery is mentioned by Davis et al. (1994) after surgically preparing vascular access ports to the femoral artery. Using dogs with surgically instrumented indwelling venous access ports into the femoral vein and using a 6 min infusion instead of a intravenous bolus injection is mentioned by... 

Krishna et al. (2002). Occasionally, such a short term infusion is recommended instead of a bolus intravenous administration (Chiou 1989, p 283). The advantage is to avoid high blood concentrations shortly after intravenous administration which may be in conflict with the assumed linear dose-exposure relationship (validity of linear relation at border concentration ). The advantage of the intravenous bolus injection is the lower/shorter stress situation for the animals (and may be also for the experimenter) which might influence the reproducibility of the study results. 

Bioavailability studies quantify rate and extent of absorption. They compare the efficiency of the disposition of several drug formulations, e.g. immediate-release vs. extended-release or capsule vs. tablet or tablet A vs. tablet B etc., or they compare the disposition of different routes of administration, e.g. oral vs. subcutaneous or oral vs. intravenous. According to the definition, a comparison to the intravenous bolus injection yields the absolute bioavailability. 

To illustrate the type of data that can be obtained using the study discussed, a high level summary of the pharmacokinetic results obtained from the study described above under Procedure is presented below. Due to the anticipated mode of action of the drug (blood pressure lowering) in this example, instead of an intravenous bolus injection an intravenous infusion over 30 minutes was chosen. 

Tenecteplase is a variant of alteplase that has been altered by six point mutations, resulting in a significant prolongation of its plasma half-life (tenecteplase tv, = 20 minutes alteplase tVl = 3-4 minutes). Tenecteplase is dosed according to body weight and given by intravenous bolus injection. 

In a double-blind randomized study in 30 women in the recovery room a single intravenous bolus injection of amiphenazole 150 mg was compared with placebo amiphenazole did not improve ventilation (6). However, in a double-blind study amiphenazole reversed respiratory depression and analgesia due to morphine (7). 

Gadobenate dimeglumine (intravenous bolus injection of 0.05 mmol/kg) was well tolerated by 103 patients (mean age 56 years) with acute myocardial infarction... 

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