Administration: Suppository

Suppository administration of therapeutic ketamine is less common than other administration routes. However, suppository administration can still offer some benefits and raise specific concerns. Here, we discuss the benefits, problems, dosing, and bioavailability of suppository administration of therapeutic ketamine.


  1. Non-invasive: Suppository administration is a non-invasive method that may be more acceptable to patients uncomfortable with injections.
  2. Ease of administration: Suppositories are simple and easy to administer, requiring no assistance from healthcare professionals.
  3. Bypassing first-pass metabolism: Rectal administration bypasses the liver’s first-pass metabolism, which may lead to a more predictable response and lower doses required for therapeutic effects than oral administration (1).
  4. Suitable for patients with swallowing difficulties: Suppositories can be an alternative for patients who cannot swallow pills or tolerate oral medications.
  5. Rectal administration avoids taste and saliva objections.
  6. Many users of the rectal ROA report significant improvement in bioavailability, albeit this isn’t confirmed in the literature. It might be a consequence of individual biology differences.


  1. Lower bioavailability: The rectal route generally has lower bioavailability compared to IM and IV administration, which require higher doses to achieve therapeutic effects (2).
  2. Variable absorption: Due to factors such as rectal pH, moisture, and individual variability, absorption can be inconsistent, leading to unpredictable therapeutic effects.
  3. Patient acceptability: Some patients may find suppository administration uncomfortable or socially stigmatizing, limiting its acceptability.

Dosing and Bioavailability:

There is limited data available on the dosing and bioavailability of ketamine suppositories, as this route of administration is less common. Dosing would likely depend on the indication and patient population, with close monitoring and titration based on individual response.

Suppositories are apt to be more expensive than lozenges. Ask your compounding pharmacy about comparative pricing. You can try the rectal ROA using RDTs by either inserting the tablet whole or crushing it, dissolving the granules in water, and injecting the solution with a syringe (without a needle). This approach may be a means of trying rectal without committing to a month’s order of suppositories. We suggest you discuss this method of using RDTs rectally with your provider first.

Pacifici GM. Clinical pharmacology of the rectal administration of drugs. An update. Clin Pharmacokinet. 1989;16(2):89-112. doi: 10.2165/00003088-198916020-00002.

Peltoniemi MA, Hagelberg NM, Olkkola KT, Saari TI. Ketamine: A Review of Clinical Pharmacokinetics and Pharmacodynamics in Anesthesia and Pain Therapy. Clin Pharmacokinet. 2016 Sep;55(9):1059-77. doi: 10.1007/s40262-016-0383-6.

Notify of

Inline Feedbacks
View all comments