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

NCT05571176 | Unknown Phase 1

• 2 other identifiers: EBrinck2021-006011-28
• Study Type: interventional
• Target: 12
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

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

Keywords

S-ketamine; hepatic UGT2B7 enzyme; pharmacokinetic interaction; morphine; hydromorphone; buprenorphine

Outcome Measures

Primary Outcomes (3)

• Area under the plasma concentration versus time curve (AUC) of morphine, hydromorphone and buprenorphine after intravenous S-ketamine infusion.

  We aim to investigate whether there is a clinically significant pharmacokinetic interaction between S-ketamine and morphine, S-ketamine and hydromorphone and S-ketamine and buprenorphine.

  Time points for the measurements after the initiation of S-ketamine infusion: 0 minutes, 60 minutes, 90 minutes, 120 minutes, 180 minutes and 210 minutes

• Peak plasma concentrations (Cmax) of morphine, hydromorphone and buprenorphine after intravenous S-ketamine infusion

  We aim to investigate whether there is a clinically significant pharmacokinetic interaction between S-ketamine, morphine, S-ketamine and hydromorphone and S-ketamine and buprenorphine.

  Time points for assessing peak plasma concentrations (Cmax) for morphine, hydromorphone and buprenorphine are the following: 0 minutes, 30 minutes, 60 minutes, 90 minutes, 120 minutes, 180 minutes, 210 minutes after the initiation of S-ketamine infusion.

• Half-life time (t1/2) of morphine, hydromorphone and buprenorphine concentrations after intravenous S-ketamine infusion.

  We aim to investigate whether there is a clinically significant pharmacokinetic interaction between S-ketamine, morphine, S-ketamine and hydromorphone and S-ketamine and buprenorphine.

  Time points for assessing half-life time of morphine, hydromorphone and buprenorphine are 0 minutes, 30 minutes, 60 minutes, 90 minutes, 120 minutes, 180 minutes and 210 minutes after initiation of S-ketamine infusion.

Secondary Outcomes (5)

• The effect of S-ketamine on brain-derived neurotrophic factor (BDNF) release

  Time points for assessments: 30 minutes, 120 minutes, 240 minutes, 360 minutes, 480 minutes and at Day1 after the intiation of S-ketamine infusion

• The effect of S-ketamine on vascular endothelial growth factor (VEGF) release

  Time points for assessments: 30 minutes, 120 minutes, 240 minutes, 360 minutes, 480 minutes and at Day1 after the intiation of S-ketamine infusion.

• The effect of S-ketamine infusion on prolactin release.

  Time points for assessments: 30 minutes, 120 minutes, 240 minutes, 360 minutes, 480 minutes and at Day1 after the intiation of S-ketamine infusion

• The effect of S-ketamine infusion on cortisol release.

  Time points for assessments: 30 minutes, 120 minutes, 240 minutes, 360 minutes, 480 minutes and at Day1 after the intiation of S-ketamine infusion

• The effect of S-ketamine infusion on thrombocyte aggregation.

  At 2 hours after initiation of S-ketamine infusion.

Study Arms (2)

S-ketamine infusion

EXPERIMENTAL

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

Drug: S-ketamine

Placebo (NaCl 0.9%) infusion

PLACEBO COMPARATOR

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

Drug: S-ketamine

Interventions

S-ketamine DRUG

S-ketamine infusion 0.29 mg/kg/h for 4 hours

Placebo (NaCl 0.9%) infusion; S-ketamine infusion

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Elina Brinck: lead

MeSH Terms

Interventions

Esketamine

Study Officials

• Tuomas Lilius, MD, PhD

  University of Helsinki

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Elina CV Brinck, MD, PhD

CONTACT

+358504286267; elina.brinck@hus.fi

Tuomas Lilius, MD, PhD

CONTACT

+358404843931; tuomas.lilius@hus.fi

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: This is a double-blind study. Study participants, investigators, care providers and personnel collecting samples are blinded. Personnel preparing study drugs will not participate on conducting the study. On the first phase of the study, study participants will be administered one of the study drug infusions (either S-ketamine or placebo). The order of the study drug is random. On the second phase, study participants will be administered the other study drug (S- ketamine or placebo) that she/he did not receive on the first phase.
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: MD, PhD

Model Details: This is a cross-over study with two phases on 12 healthy volunteers. Study participants will be administered S-ketamine 0.29mg/kg/h intravenously or placebo (NaCl 0.9%) for 4 hours. 30 minutes after the initiation of the study drug infusion, each subject will be given single boluses of morphine 0.01mg/kg, hydromorphone 0.002mg/kg and buprenorphine 0.003mg/kg IV. We will analyze pharmacokinetic parameters (Cmax, tmax, AUC, t1/2) for morphine, hydromorphone, and buprenorphine. The aim of the study is to evaluate whether S-ketamine has a pharmacokinetic interaction with the opioids (morphine, hydromorphone, buprenorphine) known to be metabolized via liver UGT2B7 enzyme.

Study Record Dates

• First Submitted: September 28, 2022
• First Posted: October 7, 2022
• Study Start: January 1, 2023
• Primary Completion: June 1, 2023
• Study Completion: December 1, 2023
• Last Updated: October 7, 2022

Record last verified: 2022-09

Data Sharing

• IPD Sharing: Will not share