KetaMoHydBup: Pharmacokinetic Interaction of S-ketamine, Morphine, Hydromorphone and Buprenorphine

Elina Brinck

Status and phase: Not yet enrolling; Phase 1

Conditions: The Effect of S-ketamine on Pharmacokinetics of Morphine, Hydromorphone, and Buprenorphine

Treatments: Drug: S-ketamine

Study type: Interventional

Funder types: Other

Identifiers

NCT05571176

2021-006011-28 (EudraCT Number)

EBrinck

Details and patient eligibility

About

S-ketamine is often administered as a part of multimodal analgesia to reduce postoperative pain and postoperative opioid consumption. Current data indicates that ketamine may be useful for patients with prior use of opioids whereas the benefit for opioid-naive patients is less clear. However, different opioids have variable pharmacokinetic characteristics. Therefore, it is important to evaluate S-ketamine's effect on the pharmacokinetics of opioids.

Full description

S-ketamine is often used as a part of multimodal analgesia to reduce postoperative pain and opioid consumption, in part by mitigating opioid tolerance and opioid-induced hyperalgesia. However, there are mixed results concerning the effect of ketamine for this indication. Different opioids have various pharmacokinetic characteristics. Ketamine is known to inhibit the liver UGT2B7-enzyme, that is responsible for e.g., morphine metabolism. Therefore, it is important to investigate whether there is a clinically important pharmacokinetic interaction between S-ketamine and opioids metabolized via liver UGT2B7 enzyme. These opioids include morphpine, hydromorphone and buprenoprhine.

Enrollment: 12 estimated patients

Sex: All

Ages: 18 to 45 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• written informed consent
• age 18-45 years
• healthy
• Normal values in the following laboratory assessments: Hb, P-ALAT, P-AFOS, P-GT, P-creatinine, P-K, P-Na, chemical sample for urine (U-KemSeul). Pregnancy test (P-hCG-tot) must be negative.
• Urine sample for detection of any illegal drugs must be negative (U-Huum-PS)
• Normal EKG
• Normal blood pressure
• No prior use of illicit drugs

Exclusion criteria

• Tendency/predisposition to illicit drug use, illicit drug use in history
• Abnormal EKG
• smoking
• use of oral contraceptives
• pregnancy, lactation
• participating in a less tha 3 months ago
• Blood donation less than 3 months ago
• The subject's peripheral veins are hardly visible (predisposing difficulties in cannulation)
• weight less than 50 kg, body mass index (BMI) less than 18,5 or over 30

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Quadruple Blind

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12 participants in 2 patient groups, including a placebo group

S-ketamine infusion

Experimental group

Description:

12 healthy volunteers, S-ketamine infusion 0.29 mg/kg/h for 4 hours

Treatment:

Drug: S-ketamine

Placebo (NaCl 0.9%) infusion

Placebo Comparator group

Description:

12 healthy volunteers, placebo (NaCl 0.9%) infusion for 4 hours

Treatment:

Drug: S-ketamine