Drug administration repetitive

Restricted diffusion also limits tissue distribution after intraparenchymal drug administration, as shown in Figure 2.7c and d. Distribution has been measured in the rat brain after implantation of polymer discs containing NGF [66]. Drug concentrations decreased to less than 10% of the values measured on the disc surface within a distance of 2-3 mm, even after prolonged periods of several days. Therefore, applying this approach in the larger human brain would require the stereotaxic placement of multiple intraparenchymal depots, as has been evaluated in rat brain [67], on a repetitive schedule. 

In most clinical situations, drugs are administered in a series of repetitive doses or as a continuous infusion to maintain a steady-state concentration of drug associated with the therapeutic window. Calculation of the appropriate maintenance dosage is a primary goal. To maintain the chosen steady-state or target concentration, the rate of drug administration is adjusted such that... 

If an immediate effect is needed, a loading dose (Dload) must be given to administer the therapeutic amount (Dload = Ao). To maintain the drug effect, the maintenance dose (D) must be administered repetitively with the administration interval (Tau). 

If a drug is given repetitively with a constant dose (D) and a constant administration interval (Tau) accumulation occurs until a steady-state concentration (Css) is obtained after 4.32 times the elimination half-life (/ss -4.32 Tl/2). 

The subjective effects of all the psychostimulants depend on personality, the environment in which it is administered, the dose of the drug, and the route of administration. For example, moderate doses of D-amphetamine (10-20 mg) in a normal person will produce euphoria, a sense of increased energy and alertness, anorexia, insomnia, and an improvement in the conduct of repetitive tasks. Some people become anxious, irritable and talkative. As the dose of amphetamine is increased, the symptoms become more marked and the influence of the environment less pronounced. 

Fig. 3. The plasma concentration of drug in the patient as a function of time after administration ---) traditional delivery system with repetitive administration ( ), (-) prolonged...

Arnold, R. D., Mager, D. E., Slack, J. E., and Straubinger, R. M. (2005), Effect of repetitive administration of Doxorubicin-containing liposomes on plasma pharmacokinetics and drug biodistribution in a rat brain tumor model, Clin. Cancer Res., 11, 8856-8865. 

Some drugs, such as rifampin, induce their own metabolism. During repetitive administration of rifampin at a daily dose of 600 mg for 30 days, the elimination half-lives of rifamprin were 4.2 and 1.9 h on the first and last days, respectively. Carbamazepine also shows pronounced self-induction. The plasma concentrations at steady state predicted from single-dose data were two to three times higher than the actual concentrations observed during chronic treatment. 

Ullrich A, Berg C, Hengstler JG, Runge D (2007) Use of a standardised and validated long-term human hepatocyte culture system for repetitive analyses of drugs repeated administrations of acetaminophen reduces albumin and urea secretion. ALTEX 24(1) 35M 0... 

When an initially painful intravenous or intramuscular injection must be administered repetitively, patient reluctance develops. Injection pains are usually accompanied by hemorrhage, edema, inflammation, and tissue necrosis." Among the factors responsible for painful injections, the most important are the drug solubility in aqueous medium, the viscosity, the pH and the hypo- or hyperosmotic character of the injected drug solution, the amount of the injected volume, the site of injection, the pain tolerance of the patient, and the technique of administration. Other factors include precipitation of the drug at the injection site, and localized cell lysis. ... 

Hypnotic doses of barbiturates increase the total sleep time and alter the stages of sleep in a dose-dependent manner. Like the benzodiazepines, these drugs decrease sleep latency, the number of awakenings, and the durations of rapid-eye-movement (REM) and slow-wave sleep. During repetitive nightly administration, some tolerance to the effects on sleep occurs within a few days, and the effect on total sleep time may be reduced by as much as 50% after 2 weeks of use. Discontinuation leads to rebound increases in all the parameters reported to be decreased by barbitmates. 

All of these barbiturates will accumulate during repetitive administration unless appropriate adjustments in dosage are made. Furthermore, the persistence of the drug in plasma during the day favors the development of tolerance and abuse. 

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.

If perioperative antibiotic prophylaxis is indicated, responsibility for drug choice, timing and administration must be clear to all. Typical antibiotics for perioperative prophylaxis in vascular surgery target bacterial colonization at the surgical site, such as cephalosporin (e.g. cefazoline, cefuroxime). To achieve adequate tissue concentration, a time interval between i.v. administration and skin incision of 30-60 min is mandatory. The dose of a single shot antibiotic prophylaxis is not adapted to renal clearance, but repetition doses may require adaptation. 

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