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Rectal drug administration
Dr Mohammad Issa
Rectal drug administration advantages
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a relatively large dosage form can be
accommodated in the rectum
the rectal route is safe and convenient for elderly
and young patients
drug dilution is minimized as the residual fluid
volume is low
the rectum is generally empty
absorption adjuvants have a more pronounced
effect than in the upper gastrointestinal tract
degradative enzymes in the rectal lumen are at
relatively low concentrations
therapy can easily be discontinued
first-pass elimination of drug by the liver is partly
avoided
Barriers for drug absorption following
rectal administration
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If the drug is administered as a suppository,
melting or liquefaction of the base has to occur
and the degree of this will partly determine the
spreading of the dose through the rectum. The
drug must then dissolve in the limited rectal fluid
available, which has been estimated to be
between 1 and 3 ml
The amount of drug available for absorption can
be further reduced by degradation by luminal
contents, adsorption to luminal contents and
defaecation. The drug must then diffuse across
the unstirred water and mucous layers adjacent
to the epithelium
Drug absorption and avoidance of firstpass metabolism
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Drugs may be absorbed across the epithelial cell or via
tight junctions, and it is believed that only passive
transport occurs
Venous return from the colon and upper rectum is via
the portal vein to the liver. If a drug is delivered to the
upper part of the rectum, it is transported into the
portal system, and is therefore subject to first pass
metabolism in the liver.
The only way of avoiding first-pass metabolism is to
deliver the drug to the lower part of the rectum
A 100% increase in the availability of lignocaine was
demonstrated when administered rectally rather than
orally, and it was calculated that the mean fraction of
the rectally administered dose escaping first-pass
metabolism was 57%
Dosage forms for rectal delivery
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Suppositories: are normally either solid
suspensions or solid emulsions
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Rectally administered gelatin capsules:
can contain liquid formulations
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Enema: Micro-enemas have a volume of
between 1 and 20 ml and macro enemas
50 ml or more, both of which may be
administered as either solutions or
suspensions
Adjuvants and enhancers
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Transport from the rectal epithelium
primarily involves two transport
processes: paracellular and transcellular
routes.
As in other parts of the gut, the opening
of tight junctions by absorption enhancers
has been extensively investigated
Putative enhancers include enamine
derivatives, salicylates, calmodulin
inhibitors, surfactants, chelating agents,
fatty acids and lectins
Adjuvants and enhancers
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Bioavailability of a small peptide such as
vasopressin is increased to nearly 30% in
the presence of sodium
taurodihydrofusidate
It should always be borne in mind that
the enhancement via the paracellular
route is non-selective, with the risk of
absorption of bacterial endotoxins caused
by lysis of bacterial cell walls
Therapeutic agents administered
rectally
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Anticonvulsants
Preoperative medication and induction of
anaesthesia
Analgesics and antiarthritics
Antiemetics
Antibacterial agents
Xanthines
Drugs in inflammatory bowel disease
Cardiovascular active drugs