Understanding Ketamine’s Pathways: How Different Routes of Administration Affect Its Efficacy

Normal people who have not studied pharmacology or medicine have a perfectly reasonable idea that if a medicine gets into your body it works. Unfortunately it’s not that simple and this is the reason meds have different forms and routes of administration.

Ketamine exhibits different pharmacokinetic properties depending on its route of administration. Here’s an overview of how absorption and bioavailability vary for ketamine when delivered intranasally, sublingually, orally, intravenously, and intramuscularly:

Intranasal Administration

• Absorption: Rapid absorption through the nasal mucosa.
• Bioavailability: Approximately 15-40%
• Onset: Quick, usually within 5-15 minutes.
• Peak Levels: Reached in about 15-30 minutes.
• Duration: Shorter compared to oral administration, with effects lasting around 1-2 hours.
• Sublingual Administration
• Absorption: Absorbed through the mucous membranes under the tongue.
• Bioavailability: Estimated at around 20-50%.
• Onset: Intermediate, with effects beginning in about 15-30 minutes.
• Peak Levels: Typically achieved in 30-60 minutes.
• Duration: Effects can last 1-2 hours, but variability is higher due to incomplete absorption and potential swallowing of the drug.

Oral Administration

• Absorption: Absorbed through the gastrointestinal tract.
• Bioavailability: Low, approximately 0-20%, due to significant first-pass metabolism in the liver.
• Onset: Slower, generally within 30-60 minutes.
• Peak Levels: Reached in 1-2 hours.
• Duration: Effects can last 2-4 hours, but this can vary depending on individual metabolism.

Intravenous (IV) Administration

• Absorption: Immediate, as the drug is delivered directly into the bloodstream.
• Bioavailability: 100%, as there is no first-pass metabolism.
• Onset: Very rapid, within seconds to a few minutes.
• Peak Levels: Achieved almost immediately.
• Duration: Effects are short-lived, usually 30 minutes to an hour.

Intramuscular (IM) Administration

• Absorption: Rapid absorption from the muscle tissue.
• Bioavailability: High, around 90-95%.
• Onset: Fast, within 5-10 minutes.
• Peak Levels: Reached in about 10-20 minutes.
• Duration: Effects can last 1-2 hours.

Summary of Key Points

• Intranasal: Quick onset and moderate bioavailability, suitable for rapid, non-invasive administration.
• Sublingual: Intermediate onset and bioavailability, but variable due to potential swallowing.
• Oral: Slow onset and low bioavailability due to first-pass metabolism, with longer-lasting effects.
• IV: Immediate onset and 100% bioavailability, ideal for controlled, precise dosing.
• IM: Rapid onset and high bioavailability, providing a balance between IV and intranasal routes.