Rectal drug administration

AG De Boer, F Moolenaar, LGJ de Leede, DD Breimer. Rectal drug administration clinical pharmacokinetic considerations. Clin Pharmacokinet 7 285-311, 1982. 

Rectal Administration Rectal administration of a drug may be applied when the patient is unable to take the drug orally and some other routes are impractical. The drug administered via the rectum is absorbed and partially bypasses the liver. However, the absorption of drugs may be unreliable in certain cases. 

Rectal bioavailability and pharmacokinetics. Serenoa repens extract, administered rectally to 12 healthy male volunteers at a dose of 640 mg/person, produced the mean maximum concentration in plasma of nearly 2.60 (Xg/mL approx 3 hours after administration, with mean value for the area under the curve AUC 10 (Xg/hour/mL. The bioavailability and pharmacokinetic profile were similar to those observed after oral administration. T j occurred approx 1 hour later, and plasma concentration 8 hours after drug administration was still quantified. The drug tolerability was good, and no adverse effect was observed ". Serenoa repens capsules, administered orally at a dose of 160 mg four times daily or rectally 640 mg daily for 30 days to 60 patients with BPH, produced no significant differences in diminu-... 

This chapter focuses on rectal drug administration, which represents one of the most common routes of transmucosal drug delivery, and some aspects of rectal drug absorption, including enhancement strategies. 

In the past two decades, many studies have tested adjuvants that act by either permeabilizing the rectal mucosa or inhibiting drug degradation. Oral and rectal routes of drug administration are unsuitable for adequate absorption of various compounds with a peptide or protein structure and of several hydrophilic antibiotics. The use of absorption enhancers, e.g., salicylates, enamines, surfactants, and straight-chain fatty acids, has gained wide interest... 

New Types of Absorption Enhancing Systems Used in Rectal Drug Administration... 

Van Hoogdalem, E.J., A.G. De Boer, and D.D. Breimer. 1991. Pharmacokinetics of rectal drug administration, Part I. General considereations and clinical applications of centrally acting drugs. Clin Pharmacokinet 21 11. 

De Boer, A.G., et al. 1982. Rectal drug administration Clinical pharmacokinetic consideration. Clin Pharmacokinet 7 285. 

De Leede, L.G.J., et al. 1984. Site specific rectal drug administration in man with an osmotic system Influence on first-pass elimination of lidocaine. Pharm Res 1 129. 

As mentioned above, the rectal route is very attractive for systemic delivery of peptide and protein drugs, but rectal administration of peptides often results in very low bioavailability due to not only poor membrane penetration characteristics (transport barrier) but also due to hydrolysis of peptides by digestive enzymes of the GI tract (enzymatic barrier). Of these two barriers, the latter is of greater importance for certain unstable small peptides, as these peptides, unless they have been degraded by various proteases, can be transported across the intestinal membrane. Therefore, the use of protease inhibitors is one of the most promising approaches to overcome the delivery problems of these peptides and proteins. Many compounds have been used as protease inhibitors for improving the stability of various peptides and proteins. These include aprotinin, trypsin inhibitors, bacitracin, puromycin, bestatin, and bile salts such as NaCC and are frequently used with absorption enhancers for improvement in rectal absorption. 

Various characteristics of the molecule influence its chances of reaching its target receptor since they influence the nature and extent of the body s effect on it. A drug s pharmacokinetic profile therefore determines the extent of the drug s opportunity to exert its pharmacodynamic effect. While there are various routes for human drug administration (oral rectal intravenous, subcutaneous, intramuscular, and intra-arterial injections topical and direct inhalation into the lungs), the most common for small-molecule drugs is oral administration, and discussions in the first part of this chapter therefore focus on oral administration. (In contrast, biopharmaceuticals are typically administered by injection, often directly into the bloodstream.)... 

Today, there are a number of methods that can be used to introduce a drug into the body. Because of its convenience, the most common delivery system is the oral route. However, sometimes the oral route is not the most appropriate. In addition to the oral route, some of the alternative routes of drug administration with the oldest history include, not surprisingly, inhalation, and, surprisingly, rectal and vaginal, as illustrated by the following examples. 

One of the key pieces to development of a successful drug product is the ability to deliver the drug to the site of action with minimal discomfort or inconvenience to the patient. For small molecule therapeutics, there is a wide range of options available for drug administration. Delivery via injection (IV, IM, and SC), oral, nasal, ocular, transmucosal (buccal, vaginal, and rectal), and transdermal routes is possible with small molecule drugs. However, the size of proteins and the complexity of their structures severely limit the routes of administration available to proteins. 

Caldwell, L. Nishihata, T. Rytting, J. Higuchi, T. Lymphatic uptake of water-soluble drugs after rectal administration. J. Pharm. Pharmacol 1982, 34, 520-522. 

Central nervous system toxicity is unusual with vinca alkaloids, because they do not readily cross the blood-brain barrier. However, fatal myeloencephalopathy can occur a few hours after accidental intrathecal drug administration (58,59), with severe bilateral leg pain, and over the next 36 hours progressive leg weakness, urinary retention, meningism, fever, and somnolence. Other effects include absence of deep tendon and gag reflexes and disappearance of rectal tone. In spite of high-dose folinic acid rescue, patients became comatose, for example by the fourth day after injection, with loss of brain stem function a few days later. 

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