Intravenous drug administration bolus

The course of systemic exposure to a drug is studied by comparing intravenous (IV) administration shidies using deconvolution approach, in which r(f) is the systemic concentration produced from IV adminisfrafion (also called bolus function) and /(f) is the systemic input rate (in units such as g/min) from fhe noninfravenous (non-lV) route ... 

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 ... 

Bile secretion is studied in anesthetized bile fistula rats, which are anesthetized by an intraperitoneal injection of pentobarbital sodium (60 mg/kg), tracheotomized, and one jugular vein per rat is cannulated for intravenous administration (bolus injection or infusion of the drug candidate). Anesthesia is maintained for up to 7 hours by subcutaneous infusion of pentobarbital sodium (adjusted to the aesthetic depth of the individual animal about 24 mg/kg/h). Body temperature is monitored with a rectal probe thermometer, and temperature is maintained at 37 °C by means of a heated surgical plate. 

The kinetic parameters of the noncompartmental model are those defined previously for the accessible pool and system. However/ the formulas depend upon the experimental protocol/ especially on the mode of drug administration. In this chapter/ only the canonical inputs will be considered/ such as an intravenous bolus (or multiple boluses) or constant infusion (or multiple constant infusions). References will be given for those interested in more complex protocols. 

Because considerable time may elapse before a steady-state condition is attained as a result of repeated drug administration, it often is desirable to administer a large dose initially (i.e., loading dose) to achieve the desired drug levels immediately. Equation 9.42, which describes the time course of drug concentration after a single intravenous bolus dose, may be written as... 

For the 250 mg tablet (AUC)p = 6.6131 pgmL" h and WC=32340mLh (obtained from intravenous bolus data and assumed to be independent of the route of drug administration). 

Drug overdose Life-threatening flecainide intoxication in a 2-year-old toddler occurred when syringes used for oral administration were accidentally reversed, producing a fivefold flecainide overdose 3 hours after drug administration he developed a bradycardia of 50/minute and had a cardiopulmonary arrest, requiring resuscitation and adrenaline, after which the bradycardia recurred, followed by a wide-complex tachycardia that converted rapidly to a narrow-complex tachycardia after bolus intravenous adrninistration of sodium bicarbonate [60 ]. He then remained hemo-dynamicaUy stable and in sinus rhjflhm. The serum flecainide concentration was 0.7 mg/1. 

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. 

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. 

Injection Slow infusion of injection is preferable to bolus administration. Rapid infusion of digitalis glycosides has been shown to cause systemic and coronary arteriolar constriction, which may be clinically undesirable. Caution is thus advised and injection probably should be administered over a period of 5 minutes or more. Mixing injection with other drugs in the same container or simultaneous administration in the same intravenous line is not recommended. 

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. 

Route of administration Orthoclone OKT3 is administered as an intravenous bolus over less than one minute. The preparation should not be administered by infusion or in conjunction with other drug solutions. 

These result from the drug s sympathoplegic actions. The major adverse effect is postural hypotension. This effect can be almost totally prevented by concomitant administration of a tricyclic antidepressant agent such as protriptyline. Nausea and vomiting may occur after the intravenous administration of a bolus of bretylium. 

Plasma concentration profiles after buccal administration of the saturated drug solution varied considerably between animals but the overall time dependency was similar (Figure 4). Plasma levels increased rapidly after application of the solution onto the mucosa to produce relatively constant concentrations in the range 1500-8000 ng/ml after 2 h. Following removal of the solution the drug exhibited the expected decline in plasma concentrations at a rate comparable to that observed in the intravenous bolus study. 

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