Are kappa (ketamine) tabs equivalent to an oral solution?

Ketamine Tablets vs Oral Solution: Bioequivalence

There is no evidence that ketamine tablets ("kappa tabs") and oral ketamine solution are bioequivalent formulations, and critically, oral ketamine has poor bioavailability (approximately 17-24%) due to extensive first-pass metabolism regardless of formulation. 1, 2

Key Pharmacokinetic Considerations

Oral ketamine has inherently poor bioavailability compared to other routes of administration, making it a suboptimal choice for clinical use regardless of whether tablets or solution are used 2:

• Oral bioavailability is only 17-24% due to extensive first-pass hepatic metabolism via CYP3A4 and CYP2B6 enzymes 2
• This contrasts sharply with parenteral routes: intravenous (100%), intramuscular (93%), subcutaneous (similar to IM), intranasal (45-50%), and sublingual (30%) 1, 2

Formulation-Specific Issues

No comparative data exists between ketamine tablets and oral solution formulations 1, 2:

• The literature on ketamine administration focuses on route of administration rather than comparing different oral formulations 1
• Unlike other medications where oral solutions may have different absorption profiles than tablets, ketamine's primary limitation is the route itself (oral), not the specific formulation 2

Clinical Implications for Route Selection

Alternative routes should be strongly considered over any oral formulation for ketamine administration 1:

• Intranasal administration produces rapid maximum plasma concentrations with relatively high bioavailability (45-50%) and is practical for outpatient use 1, 2
• Sublingual/transmucosal routes offer better bioavailability (approximately 30%) than oral administration 1, 2
• Subcutaneous and intramuscular routes are safe, effective, and can be administered as bolus injections with bioavailability exceeding 90% 1

Dosing Considerations

If oral ketamine must be used, expect to require substantially higher doses than parenteral routes 1, 2:

• The conversion ratio from IV to oral is approximately 1:3 to 1:5 due to poor bioavailability 2
• Standard IV ketamine dosing for depression is 0.5 mg/kg, but oral doses studied range from 0.5-3 mg/kg to achieve similar effects 1

Safety and Abuse Potential

Oral formulations carry specific risks that must be considered 1:

• Domiciliary (home) treatment with oral ketamine increases abuse risk compared to clinic-based parenteral administration 1
• The longer time to peak effect with oral administration (1-2 hours) may lead to dose stacking if patients re-dose prematurely 2

Common Pitfalls to Avoid

• Do not assume oral tablets and solutions are interchangeable without specific bioequivalence data for ketamine formulations
• Do not use oral ketamine when rapid onset is needed—the 1-2 hour time to peak concentration makes it unsuitable for acute situations 2
• Do not overlook alternative routes that offer superior bioavailability and more predictable pharmacokinetics 1, 2