Rectal drugs

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

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 ... 

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. 

Breimer, D.D., et al. 1985. Rate controlled rectal drug delivery. In Rate control in drug therapy, eds. L.F. Prescott, and W.S. Nimmo, 54. Edinburgh Churchill Livingstone. 

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. 

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... 

However, some negative effects of the combination of CyDs and polysaccharide on the rectal drug delivery were reported. Lin et al. [38] demonstrated that the mixture of (3-CyD and hydroxypropylmethylcellulose (HPMC) markedly reduced the in vivo bioavailability of acetaminophen from both aqueous solution and hydrogels. Not only the lower partition coefficient but also the higher hydrophilic property of the (3-CyD complex and the higher viscosity of HPMC hydrogel matrix might be responsible for the decrease in the in vitro permeation rate and depression of in vivo rectal absorption of acetaminophen. 

Yamamoto, A., and S. Muranishi. 1997. Rectal drug delivery systems—Improvement of rectal peptide absorption by absorption enhancers, protease inhibitors and chemical modification. 

Miyazaki, S., et al. 1995. Thermally gelling poloxamine Synperonic T908 solution as a vehicle for rectal drug delivery. Biol Pharm Bull 18 1151. 

Miyazaki, S., Suisha, F., Kawasaki, N., Shirakawa, M., Yamatoya, K., and Attwood, D. (1998),Thermally reversible xyloglucan gels as vehicles for rectal drug delivery,/. Controlled Release, 56,75-83. 

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. ... 

Bile salts were also used for the enhancement of drug absorption, but several studies indicated severe damage due to their use in rectal drug delivery. Sodium tauro-24, 25-dihydrofusidate (STDHF) had a positive effect on the availability of cefoxitin, vasopres-sine, and insulin in rats. ... 

De Leede, L.G.J. Rate-Controlled and Site-Specified Rectal Drug Delivery Ph.D. Thesis State University of Leiden Leiden, The Netherlands, 1983. 

In certain areas of the world, particularly some European countries and Japan, rectal dosage forms are somewhat more accepted by the patient population and, hence, development of rectal dosage forms has surpassed that in the United States. According to a survey in 1970, approximately 7.5% of all prescriptions in France were formulations intended for rectal administration.Even though a few countries may find rectal dosage forms more acceptable, these still represent a small area of the world-wide market share which can be assigned to rectal drug therapy. 

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