Is there data supporting rectal administration of phenobarbital for palliative sedation?

Comment by InpharmD Researcher

There is limited data on rectal administration of phenobarbital for palliative sedation. One study compared mircoenema suspensions to suppositories and found that microenemas achieved higher plasma concentrations more rapidly and with less discomfort (Table 1). Another study focused on phenobarbital suppositories for palliative sedation in home setting as primarily indicated for agitated delirium, providing an alternative for individuals who desire to avoid hospitalization (Table 2). While a dated pharmacokinetic study indicated effective rectal absorption of phenobarbital, its relevance to palliative sedation remains unclear. Further research is needed to establish the broader safety and efficacy of rectal phenobarbital administration.

Background

The 2014 European Society for Medical Oncology (ESMO) clinical practice guidelines for the management of refractory symptoms, including use of palliative sedation, indicate that the use of sedation should be tailored to the patient's preference, condition, and current therapy. Current sedative options include phenobarbital, among other medications, although the guidelines do not discuss rectal administration. [1]

One dated pharmacokinetic study aimed to determine the relative bioavailability and time course of absorption of the commercially available parenteral phenobarbital sodium solution administered rectally in comparison with the same preparation given intramuscularly. Seven healthy adult male volunteers were given 5 mg/kg dose of phenobarbital on two separate occasions five weeks apart. One dose was administered intramuscularly into the lateral aspect of the gluteus maximus, and the other was given rectally. The rectal dose was prepared in a 3 mL syringe, administered undiluted into the rectal vault, and retained for a minimum of four hours. Eighteen blood samples were drawn over 288 hours. The pharmacokinetic parameters after intramuscular and rectal administration were as follows: the area under the curve (AUC) reached 5,916 vs. 5,253 micromol*h/L; half-life (T1/2) was 112 vs. 113 hours; time to peak concentration (Tmax) occurred at 2.1 vs. 4.4 hours; and maximum serum concentration (Cmax) was 36.2 vs. 31.4 micromol/L. One participant experienced a significant reduction in absorption after rectal administration compared to the other six participants. Aside from mild drowsiness, there were no reports of subjective toxicity. With a mean relative bioavailability for rectal phenobarbital of 90%, findings suggest that the parenteral phenobarbital sodium solution given rectally is well absorbed and provides a useful alternative route of administration. These findings may not be applicable to palliative sedation scenarios, as the study was conducted on healthy volunteers and may lack generalizability to that specific context. [2]

Literature Review

A search of the published medical literature revealed 2 studies investigating the researchable question: