Intravenous drug administration continuous

Most muscle relaxants are absorbed fairly easily from the gastrointestinal tract, and the oral route is the most frequent method of drug administration. In cases of severe spasms, certain drugs such as methocarbamol and orphenadrine can be injected intramuscularly or intravenously to permit a more rapid effect. Likewise, diazepam and dantrolene can be injected to treat spasticity if the situation warrants a faster onset. As discussed earlier, continuous intrathecal baclofen administration may be used in certain patients with severe spasticity, and local injection of botulinum toxin is a possible strategy for treating focal dystonias and spasticity. Metabolism of muscle relaxants is usually accomplished by hepatic microsomal enzymes and the metabolite or intact drug is excreted through the kidneys. 

Recently, there is a growing recognition that the benefits of intravenous drug infusion can be closely duplicated, without its potential hazards, by using the intact skin as the portal of drug administration to provide a continuous transdermal drug delivery into the systemic circulation Q). 

Morphine is available for oral, rectal, and parenteral administration. Oral formulations include immediate and controlled release tablets, as well as oral solution regular strength and concentrate. Parenterally, it can be administered subcutaneously, intramuscularly, intravenously, or by continuous infusion. It is a drug of abuse and can be nasally insufflated. 

Clinical management can potentially reduce the effects of plutonium intake, although the effectiveness can be highly variable. Administration of the calcium salt of diethylenetriaminepentaacetic acid (DTPA) can accelerate removal of soluble forms of plutonium from body fluids and recent deposits. It is unable to remove intracellular deposits or activity buried in bone and must therefore be administered as soon as possible after an intake. In a review of 18 patients exposed to plutonium, americium, or curium, the US Food and Drug Administration concluded that administration of 1 g Ca-DTPA in 5 ml sterile aqueous solution, either by intravenous injection or as a nebulized inhalation dose, increased the rate of radioactivity elimination in urine by an average of 39-fold. Daily maintenance doses of Zn-DTPA resulted in continued elimination of radioactivity. 

As the rate of absorption increases, the concentration maxima approach 2 and tiie minima approach 1 during tiie steady state. The black line depicts the pattern during administration of equivalei dosage by continuous intravenous infusion. Curves are based on the one-compartment model. Average concentration (Css) when tiie steady state is attained during intermittent drug administration is... 

Figure 11.11 A plot of plasma concentration (Cp) versus time following repetitive intravenous bolus administration of a drug. The figure demonstrates the plasma level resulting from either a series of maintenance doses (dashed line) or an initial loading dose followed by a series of maintenance doses (continuous line), min, minimum max, maximum MTC, minimum toxic concentration MEC, minimum effective concentration t, dosing interval.

The development of some of the secondary models such as conditioned place preference and electrical brain stimulation which do not require intravenous drug injections will continue to occur (for complete descriptions of the conditioned place preference paradigm and validation data, see Bardo and Bevins (2000) or Cunningham et al. (2006, 2011) for a complete description of the electrical brain stimulation model, also see O Neill and Todtenkopf (2010) or McBride et al. (1999)). A better understanding of the predictivity of these models and correlation with the traditional self-administration model will be required for these models to assume a mainstream position in abuse potential assessment. The self-administration model s predictive correlation to abuse potential in humans has been well characterized but new models will have to be characterized and published to have equal impact in future abuse potential testing. 

The drug is metabolized rapidly in the liver, kidney, intestinal mucosa, and even red blood cells. Therefore it has a plasma half-life of only 10 min after bolus intravenous application. The major metabolite, uracil arabinoside (ara-U), can be detected in the blood shortly after cytarabine administration. About 80% of the dose is excreted in the urine within 24 h, with less than 10% appearing as cytarabine the remainder is ara-U. After continuous infusion, cytarabine levels in the liquor (cerebro-spinal fluid) approach 40% of that in plasma. Continuous infusion schedules allow maximal efficiency, with uptake peaks of 5-7 pM. It can be administered intrathecally as an alternative to methotrexate. 

The short plasma half-life of dobutamine (1-2 minutes) was found by Murphy et al. (4) to be due to the rapid redistribution of the drug from the plasma to the tissue. However, plasma half-life of radioactivity following the administration of 14C-dobutamine was 1.9 hours. The major circulating metabolite is the glucuronide conjugate of 3-0-methyldobutamine. During a continuous intravenous infusion of dobutamine, the plasma level of the parent drug reach a maximum within 8 to 10 minutes, while those of the metabolites peak be-... 

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. 

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