Bolus injections

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. 

Meropenem. This drug is administered only by the IV route The nurse gives meropenem every 8 hours over a period of 15 to 30 minutes if die drug is diluted or over a period of 3 to 5 minutes as a bolus injection (5-20 mL). 

Although the drug is most often administered orally, warfarin injection may be used as an alternative route for patients who are unable to receive oral drag. The intravenous dosage is the same as that for the oral drug. Intravenous warfarin is administered as a slow bolus injection during a period of 1 to 2 minutes. Warfarin is not recommended for intramuscular injection. After the drug is reconstituted, it is stable for 4 hours at room temperature. The vial is not recommended for multiple use, and any unused solution should be discarded. 

The release of steroids such as progesterone from films of PCL and its copolymers with lactic acid has been shown to be rapid (Fig. 10) and to exhibit the expected (time)l/2 kinetics when corrected for the contribution of an aqueous boundary layer (68). The kinetics were consistent with phase separation of the steroid in the polymer and a Fickian diffusion process. The release rates, reflecting the permeability coefficient, depended on the method of film preparation and were greater with compression molded films than solution cast films. In vivo release rates from films implanted in rabbits was very rapid, being essentially identical to the rate of excretion of a bolus injection of progesterone, i. e., the rate of excretion rather than the rate of release from the polymer was rate determining. 

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...

In chimpanzees, administration of Fab fragments of a monoclonal anti-F-VII antibody preceding an endotoxin bolus injection effectively blocked the activation of the coagulation pathway (B25). Administration of monoclonal anti-lL-6 under the same experimental conditions attenuated the activation of coagulation, while the fibrinolytic system remained unaltered. However, administration of monoclonal anti-TNF enhanced the tendency to microvascular thrombosis (P17,18). Monoclonal anti-TF antibodies administered to baboons as a pretreatment attenuated coagulopathy after induction of E. coli sepsis in these animals (T4). Primates pretreated with anti-C5a antibodies before infusion of E. coli developed less hypotension and had better survival rates than untreated animals, who developed ARDS and septic shock with a mortality rate of 75% (S35, Z6). No favorable treatment results have been published yet with one of these treatment modalities given to humans. 

Mallo, C., Zaidan, R., Galy, G. et al. (1990). Pharmacokinetics of melatonin in man after intravenous infusion and bolus injection. Fur. ]. Clin. Pharmacol. 38, 297-301. 

The severity of magnesium depletion and presence of symptoms dictate the route of magnesium supplementation (Table 78-7). Intramuscular magnesium is painful and should be reserved for patients with severe hypomagnesemia and limited venous access. IV bolus injection is associated with flushing, sweating, and a sensation of warmth. 

Reaction (52) occurs at the gradient interface of the bolus addition until local Hb(02) concentrations have been reduced, at which point additional NO reduces the iron(III) to iron(II) which can further react with free NO to form Hb(NO). The validity of this mechanism was verified by the observation that addition of CN- ion, which binds irreversibly to metHb to form metHb(CN), significantly attenuated the formation of Hb(NO) in both cell-free Hb and RBC. Mathematical models used to simulate bolus addition of NO to cell-free Hb and RBC were compatible with the experimental results (147). In the above experiments, SNO-Hb was a minor reaction product and was formed even in the presence of 10 mM CN, suggesting that RSNO formation does not occur as a result of (hydrolyzed) NO+ formation during metHb reduction. However, formation of SNO-Hb was not detectable when NO was added as a bolus injection to RBC or through thermal decomposition of DEA/NO in cell free Hb (DEA/NO = 2-(A/ A/ diethylamino)diazenolate). SNO-Hb was observed... 

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. 

A single bolus injection (200 pL) containing various doses of AmB of different formulations was given intravenously to groups of 10 male CDl mice (Charles River, France), weighing 25 to 30 g. Mouse survival was monitored daily for 30 days and the LD50 was determined by the method of Litchfield and Wilcoxon (27). 

There is substantial variability in the pharmacokinetics of vinblastine in patients. Evidence has been obtained that implicates altered liver function and dose-dependent elimination as contributing factors to the variable pharmacokinetics. When vinblastine was administered by a bolus injection, a mean terminal elimination half-life of 29.2 hr was estimated for a group of 24 patients, but the half-lives ranged from a low value of 16 hr to a high value of 65 hr (55). When vinblastine was administered by intravenous infusion, clearance of the drug appeared to decrease with time over a 4-month period decreases in serum albumin values were found to be correlated with decreases in the clearance of vinblastine. 

Table 2.1. Brain concentration, blood-brain barrier PS product, and plasma AUC (0-60 min) of brain delivery vectors after i.v. bolus injection.

Percentage injected dose per g brain 60 min after i.v. bolus injection. 

In a typical procedure, a continuous wave laser (50 mW) excites ICG at 780 nm and the fluorescence signal is captured at 830 nm. Subsequent to a bolus injection in the tail vein of the rat, the time-dependent clearance of ICG from plasma can be monitored in real-time as shown in Eig. 9 for three rat data sets. 

Three distinct regions are observed in the clearance curves. It begins with a region where data is gathered pre-bolus injection, and represents the baseline value for the subsequent experiments. The ICG plasma concentration rapidly peaks within a few seconds, followed by rapid exponential decay as the liver eliminates the dye from blood. Visually, the decay rates are similar for all three, and well within biological variability. After 15 minutes, approximately 90% of the initial signal is lost. The ICG elimination from blood follows the single compartment pharmacokinetics model described by Eq. (3). After several experi-... 

Fig. 9. In vivo fluorescence time-dependence for three rats with normal liver function after a bolus injection of ICG. The solid line is a single exponential fit to the measured data...

Endothelial permeabiHty can be assessed in vitro, i.e. in well-controlled experimental conditions allowing a rigorous comparison between CA and eUminating a number of parameters that may vary significantly following bolus injection in in vivo models. 

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