Rectal drug absorption

Raab, Y., Gerdin, B., Hallgren, R., Regional rectal perfusion a new in vivo approach to study rectal drug absorption in man, Pharm. Res. 1995, 12, 426-432. 

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. 

The physicochemical properties of the drug molecules and the formulation can also influence rectal drug absorption (Table 7.1). Crucial parameters in this regard include drug concentration, molecular weight, solubility, lipophilicity, pKa, surface properties, and particle size [12]. In addition, formulation properties such as the nature of the suppository base material may play a critical role in regulating drug absorption. 

TABLE 7.1 Influential Factors on Rectal Drug Absorption from Suppository ... 

Takahashi, H., et al. 1997. The enhancing mechanism of capric acid (CIO) from a suppository on rectal drug absorption through a paracellular pathway. Biol Pharm Bull 20 446. 

CYCLODEXTRINS AS MULTIFUNCTIONAL ENHANCERS FOR RECTAL DRUG ABSORPTION... 

Sodium salicylate and 5-methoxysalicylate increased the absorption of insulin. Sodium glycocholate was more effective than sodium taurocholate but less effective than sodium-deoxycholate and PE-9-laurylether in enhancing rectal insulin absorption in rabbits. The role of disodium EDTA in the enhancement of rectal drug absorption, along with the damaging effects on the rectal mucosa, has been described for several drugs. ... 

Opioids maybe administered in a variety of routes including oral (tablet and liquid), sublingual, rectal, transdermal, transmucosal, intravenous, subcutaneous, and intraspinal. While the oral and transdermal routes are most common, the method of administration is based on patient needs (severity of pain) and characteristics (swallowing difficulty and preference). Oral opioids have an onset of effect of 45 minutes, so intravenous or subcutaneous administration maybe preferred if more rapid relief is desired. Intramuscular injections are not recommended because of pain at the injection site and wide fluctuations in drug absorption and peak plasma concentrations achieved. More invasive routes of administration such as PCA and intraspinal (epidural and intrathecal) are primarily used postoperatively, but may also be used in refractory chronic pain situations. PCA delivers a self-administered dose via an infusion pump with a preprogrammed dose, minimum dosing interval, and maximum hourly dose. Morphine, fentanyl, and hydromorphone are commonly administered via PCA pumps by the intravenous route, but less frequently by the subcutaneous or epidural route. 

A review of GI transit and oral drug absorption can be organized in many ways, but a logical sequence is to start at the top and work down. In this review, techniques to study buccal and rectal delivery will not be covered, but a detailed description of these is available in a recent book (1). 

Concerning the absorption theory for organic compounds in the alimentary tract, the pH-partition hypothesis has been accepted. Under normal physiological conditions, drug absorption from the lower alimentary tract is well described by the pH-partition hypothesis. Therefore, the passive transport mechanism is dominant in drug absorption from rectal mucous membranes. On the other hand, does any specific transport mechanism, such as... 

Many physiological aspects affect drug absorption from the rectum (Table 7.1). Influential factors include the pH of the rectal contents, state of the mucus layer, volume and viscosity of rectal fluid, luminal pressure from the rectal wall on the dosage form, enzymatic and microbacterial degradation by rectal epithelium, presence of stools, and venous drainage differences within the rectosigmoid regions. 

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

Muranishi, S. 1984. Characteristics of drug absorption via the rectal route. Methods Find Exp Clin Pharmacol 6 763. 

De Boer, A.G., E.J. Van Hoogdalem, and D.D. Breimer. 1992. (D) Routes of delivery Case studies, (4) rate-controlled rectal peptide drug absorption enhancement. Adv Drug Deliv Rev 8 237. 

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