Single Dose Administration of Ketamine 10, 20, 40 and 80 mg and 5 mg Solution for Infusion in 15 Healthy Subjects
Condition: Healthy
Study type: Interventional
Phase: Phase 1

Summary: 
      This study is designed for descriptive pharmacokinetic characterization of ketamine and
      norketamine in serum, urine and feces after oral single dose administration of a new
      developed prolonged release tablet formulation containing 10, 20, 40 and 80 mg ketamine under
      fasting conditions and for descriptive pharmacokinetic characterization of ketamine and
      norketamine in serum, urine and feces after intravenous single dose administration of 5 mg
      ketamine solution for infusion within 30 min
    

Detailed description: 
      Ketamine, a cyclohexanone derivative, is a non-barbiturate anesthetic agent which has been
      available in clinical practice for more than 40 years. Ketamine was first synthesized in 1962
      and patented in Belgium in 1963. Ketamine, a potent non-competitive N-methyl-D-aspartate
      (NMDA) receptor antagonist, has a recognized unique therapeutic value in human and veterinary
      medicine as an anesthetic with analgesic properties. Ketamine is considered as one of the
      World Health Organisation (WHO) essential drugs for the management of refractory pain.

      Ketamine is widely used for the induction and maintenance of general anesthesia, usually in
      combination with a sedative and if required a muscle relaxant. When used as an intravenous
      (i.v.) or intra-muscular (i.m.) injection, ketamine is best suited for short procedures. With
      additional doses, or by i.v. infusion, ketamine can be used for longer procedures. Due to its
      pharmacodynamic properties, important clinical applications are mainly brief diagnostic ones
      and surgical procedures in paediatric patients and ambulatory anesthesia, treatment of burn
      patients, obstetrics, and for the induction and maintenance of anesthesia in trauma victims,
      hypovolemic patients, patients with septic or cardiogenic shock, and patients with pulmonary
      diseases. Other uses include sedation in the intensive care setting, and analgesia
      particularly in emergency medicine as well as treatment of bronchospasm / asthma. However,
      the use of ketamine for humans in the EU is restricted to special indications, due to the
      occurrence of emergence reactions. Outside the EU, its ease of use gives ketamine a major
      advantage under difficult circumstances (developing countries and remote areas).

      For therapeutic purposes, ketamine is usually administered intravenously (i.v.) or
      intramuscularly (i.m.). Its hydrochloride salt is marketed under many brand names such as
      Ketanest, Ketalar, or Ketaset. Ketamine is a chiral compound. While most marketed ketamine
      preparations are racemic mixtures of R-(-)-ketamine and S-(+)-ketamine (1:1), formulations
      containing only the enantiomer S-(+)-ketamine are also commercially available (e.g. Ketanest®
      S, Pfizer Pharma GmbH). S-(+)-ketamine is approximately four times more potent than
      R-(-)-ketamine and twice as potent as the racemic mixture.

      It is well-known that ketamine exerts analgesic effects at subanesthetic doses. Therefore,
      during the past 15-20 years, ketamine has been used as an analgesic in a wide range of pain
      settings, including acute (e.g. post-operative pain, pain during dental procedures) and
      chronic pain (e.g. central or peripheral neuropathic pain, cancer pain) conditions.

      Although the drug is only approved for intramuscular injection and intravenous injection or
      infusion, ketamine is frequently used via other routes of administration, such as
      subcutaneous (s.c.) injection or infusion, rectal, oral, intranasal, transdermal (patch),
      intrathecal or epidural administration. Considering that no oral formulation is approved, the
      marketed solution for injection/infusion or an extemporaneous preparation was used in
      clinical studies investigating the efficacy of orally administered ketamine. For clinical
      (off-label) use, the solution for injection/infusion is generally employed for oral
      treatment.
    

Intervention name(s): Ketamine
Intervention type(s): Drug
Intervention description(s): Intravenous infusion of 5 mg ketamine solution, diluted in 240 ml 0.9% saline within 30 min under fasting conditions on study day 1 and oral administration of one prolonged release tablet ketamine together with 240 ml table water under fasting conditions with increased dose (10, 20, 40 and 80 mg) and at least 7 days wash-out between the study days
Intervention MeSH terms: Ketamine
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Anesthetic Drugs