Sustained-release preparations, administration

Administering Oral Nitroglycerin. Nitroglycerin is also available as oral tablets tiiat are swallowed. The nurse gives tiiis form of nitroglycerin to die patient whose stomach is empty, unless the primary health care provider orders otherwise. If nausea occurs after administration, die nurse notifies die primary healdi care provider. Taking die tablet or capsule widi food may be ordered to relieve nausea The sustained released preparation may not be crushed or chewed. 

Drug/Food interactions Theophylline elimination is increased (half-life shortened) by a low carbohydrate, high protein diet, and charcoal broiled beef (due to a high polycyclic carbon content). Conversely, elimination is decreased (prolonged half-life) by a high carbohydrate low protein diet. Food may alter the bioavailability and absorption pattern of certain sustained-release preparations. Some sustained-release preparations may be subject to rapid release of their contents when taken with food, resulting in toxicity. It appears that consistent administration in the fasting state allows predictability of effects. 

Methylphenidate and D-amphetamine are both short-acting compounds, with an onset of action within 30 to 60 minutes and a peak clinical effect seen usually between 1 and 2 hours after administration, lasting 2 to 5 hours. Therefore, multiple daily administrations are required for a consistent daytime response. The amphetamine compound Adderall, the sustained-release preparations of methylphenidate and dextroamphetamine, and pemoline are all intermediate-acting compounds with an onset of action within 60 minutes and a peak clinical effect seen usually between 1 and 3 hours after administration and maintained for up to 8 hours (8 hours with metadate C.D. and Ritalin LA 12 hours with Concerta), allowing for a single dose for the entire school day. Adderall XR is a 12 hour preparation. 

Most of the drugs in this class are well absorbed after oral administration peak concentrations occur 1-3 hours after ingestion. Sustained-release preparations of propranolol and metoprolol are available. 

Improvements in theophylline preparations have come from alterations in the physical state of the drugs rather than from new chemical formulations. For example, the increased surface area of anhydrous theophylline in a microcrystalline form facilitates solubilization for complete and rapid absorption after oral administration. Numerous sustained-release preparations (see Preparations Available) are available and can produce therapeutic blood levels for 12 hours or more. These preparations offer the advantages of less frequent drug administration, less fluctuation of theophylline blood levels, and, in many cases, more effective treatment of nocturnal bronchospasm. 

After a single oral dose of 20 mg to 1 subject, a peak plasma concentration of about 0.02 ig/ml was attained in about 1.5 hours following administration of 40 mg to the same subject as a sustained-release preparation, a maximum plasma concentration of about 0.08 pg/ml was reported after about 2.5 hours (P. J. Meffin et ai, ibid.). 

The drug is absorbed rapidly and almost completely from the digestive tract. It reaches peak plasma levels within I hour after administration in gelatin capsules. Oral formula lions on (he market are sustained-release preparations providing peak plasma levels 3 to 4 hours after administration. 

A single oral dose (200 to 400 mg) of etodolac (Lodine) provides postoperative analgesia that typically lasts for 6 to 8 hours. Etodolac also is effective in the treatment of osteoarthritis and rheumatoid arthritis, and the drug appears to be uricosuric. A sustained-release preparation (Lodine XL) is available, allowing once-a-day administration. 

Theophylline administered in liquids or uncoated tablets is absorbed rapidly and completely. In the absence of food, solutions or uncoated tablets of theophylline produce maximal concentrations in plasma within 2 hours and maximal plasma concentrations are achieved within I hour. Numerous sustained-release preparations of theophylline are available, designed for dosing intervals of 8, 12, or 24 hours. There is marked interpatient variability in the rate and extent of absorption, and especially in the effect of food and time of administration on these parameters. Thus, it is necessary to avoid substituting one apparently similar product for another. 

The United States is considering the development of sustained-release forms of pyridostigmine that would permit maintenance of an adequate level of AChE inhibition with once-daily oral administration. To date, however, no sustained-release preparation has shown sufficient promise to warrant advanced testing. Unfortunately as well, efforts to provide transdermal delivery of pyridostigmine with skin patches have had disappointing results, as would be expected because of the polar nature of the compound. 

Hospital. Administer activated charcoal. Consider gastric lavage for all but the most trivial ingestions. For large ingestions of a sustained-release preparation, consider whole-bowel irrigation (see p 52) in addition to repeated doses of charcoal (see p 57). Continue charcoal administration for up to 48-72 hours. 

Similar findings suggesting presystemic GI inversion with ibuprofen have been described by Avgerinos and Hutt [92]. However, a C ax S/R ratio alone does not unequivocally demonstrate inversion this is only demonstrated through an increase in ratio with an increase in 7) ax- Other laboratories have also shown a similar trend of increasing C ax S/R ratio with prolongation of T ax [93]. After administration of racemic ibuprofen to humans, the Tmax values for the enantiomers were found to be identical, but the mean Cmax for the S-ibuprofen exceeded that of the R-isomer [94]. Absorption rate dependency of ibuprofen inversion has also been demonstrated in the rat [95]. Theoretical proof of this presystemic inversion was put forward employing newly developed pharmacokinetic equations [96]. Furthermore, food-induced reduction of the rate of ibuprofen delivery may mimic the effect of a sustained release preparation and also supports the concept of presystemic GI inversion [97]. 

Figure 6.16 A schematic piot of different drug administration routes. (A) Singie dose preparation (B) sustained release preparation (C) prolonged release preparation.

If disturbances of gastrointestinal function prevent the use of oral sustained-release morphine, the fentanyl transdermal system (fentanyl patch) can be used over long periods. Furthermore, buccal transmucosal fentanyl can be used for short episodes of breakthrough pain (see Alternative Routes of Administration). Administration of strong opioids by nasal insufflation has been shown to be efficacious, and nasal preparations are now available in some countries. Approval of such formulations in the USA is growing. In addition, stimulant drugs such as the amphetamines have been shown to enhance the analgesic actions of the opioids and thus may be very useful adjuncts in the patient with chronic pain. 

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