Rectal Dosing

Diazepam (Valium injection, Diastat rectal gel) IV 0.2-0.3 mg/kg over 2-5 minutes PR 2-5 years 0.5 mg/kg 6-11 years 0.3 mg/kg greater than 12 years 0.2 mg/kg Maximum dose in children less than 5 y 5 mg Maximum dose in children greater than 5 y 15 mg A second rectal dose can be given 4-12 hours after the first dose if necessary... 

The hepatic first-pass effect can be avoided to a great extent by use of sublingual tablets and transdermal preparations and to a lesser extent by use of rectal suppositories. Sublingual absorption provides direct access to systemic—not portal—veins. The transdermal route offers the same advantage. Drugs absorbed from suppositories in the lower rectum enter vessels that drain into the inferior vena cava, thus bypassing the liver. However, suppositories tend to move upward in the rectum into a region where veins that lead to the liver predominate. Thus, only about 50% of a rectal dose can be assumed to bypass the liver. 

Fig. 10.1 Rat colon tissue (A) or liver tissue (B) oligonucleotide concentrations as a percentage of administered radioactive dose for normal rats (filled symbols) or treated with trinitrobenzene sulfonic acid (open symbols) as a model for colitis. Solid lines represent intravenous route broken lines designate rectal dosing (both 100 mg/kg ISIS 2302 with nonexchangeable 3H label).

The presence of medium chain fatty acids and glycerides in food products has stimulated interest in their potential utility as absorption enhancers. Some fatty acids and glycerides have been shown to increase drug absorption under a variety of conditions, almost always in animals and in most cases after rectal dosing. However, some studies have yielded positive results after oral dosing. Oral insulin bioavailability was increased to 9-13% relative to IM administration by a mixture of sodium dodecanoate and cetyl alcohol. Aftiraxone absorption was enhanced by glyceryl-1-monooctanoate after oral, duodenal, and rectal administration to animals. 

The interaction of fluconazole with bromazepam has been studied in 12 healthy men in a randomized, double-blind, four-way, crossover study (76). They received single oral or rectal doses of bromazepam (3 mg) after 4-day pretreatment with oral fluconazole (100 mg/day) or placebo. Fluconazole caused no significant changes in the pharmacokinetics and pharmacodynamics of oral or rectal bromazepam. 

Paraldehyde is the cyclic trimer of acetaldehyde, a colorless or slightly yellow-colored liquid. It has been used as an anticonvulsant, but because of its adverse effects and because it is difficult to use it has been replaced by more modern agents. However, it is still sometimes used to treat status epilepticus that is resistant to first-line drugs (1). The usual adult rectal dose is 10-20 ml. 

Historically, rectal or intravenous paraldehyde has been used for refractory GCSE. Although effective, it is extremely difficult to administer, is associated with serious adverse effects (e.g., hypotension, tachycardia, pulmonary edema, and polyethylene emboli), and is no longer manufactured in the United States. The only available formulation currently licensed is an enteral product that is difficult to obtain in a timely manner. If a rectal dose is given, it should be diluted 1 1 in vegetable oil and given every 20 minutes as needed via a rubber catheter."... 

A mean peak plasma drug concentration of 2.6 mg/L of the "second component" with a high-performance liquid chromatography (HPLC) retention time of 26.4 min was measured in 12 healthy young men after a single oral dose of 320 mg of saw palmetto. The time to peak concentration occurred 1.5 h after administration (De Bemardi Di Valserra et al., 1994). A 640-mg rectal dose of saw palmetto extract produced a peak of 2.6 pg/rnL occurring 3 h after the dose (De Bemardi Di Valserra and Tripodi, 1994). 

Beginning in 1985, a series of patents was issued for the use of ibogaine as a rapid means of interrupting addiction to narcotics (morphine and heroin) (3), cocaine and amphetamine (4), alcohol (5), nicotine (6) and polydrug dependency syndrome (35). These patents claim that an oral or rectal dose of ibogaine (4-25 mg/kg) interrupts the dependence syndrome, allowing patients to maintain a drug-free lifestyle for at least 6 months. 

Figure 14. Uses of isotropic optical fiber fluence probes for different applications, (a) interstitial probes placed into dog prostate during an intraoperative experimental procedure (courtesy Drs F. Hetzel and Q. Chen, Denver, USA) source fibers irradiating the prostate surface, bladder and bowel are also seen, (b) a probe on the surface of a transrectal ultrasound applicator to monitor the rectal dose during interstitial PDT of prostate cancer, (c) corresponding interstitial probes placed into the prostate, along with source fibers, through a template (courtesy Dr J. Trachtenberg, Toronto, Canada).

Rectal absorption of an active substance proceeds, usually, more slowly and less completely than oral absorption. The active substance can only be absorbed after melting or dissolution of the base and dissolution of the active substance in the rectum fluid. These processes take time. Additionally, the surface for rectal absorption is much smaller than for oral absorption. Literature often advises higher standard dosages for rectal administration. The rectal dose of carbamazepine, for example, is for children 125 % of the oral dose [6]. No universal guidance could be found for the dose correction for rectal administration. When a rectal dosage cannot be found in literature the safest approach is to use the oral dosage. 

Several systems for dosage syringes are commercially available (Oral-dose, Rectal dose, Baxa and Dose-pac Fig. 24.12). 

Sanders, S.W., Haering, N., Mosberg, J. and Jaeger, H. (1986) Pharmacokinetics of ergotamine in healthy volunteers following oral and rectal dosing. Eur. J. Clin. 

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