A study to evaluate whether increased codeine levels are seen when both codeine and ketamine are given in small doses to well volunteers.
Mechanistic basis for the use of ketamine as an adjuvant to opioid analgesia – a pharmacokinetic drug-drug interaction study to define any clinically relevant drug to drug interaction between codeine and ketamine in healthy volunteers.
Flinders University- Department of Clinical Pharmacology
10 participants
Dec 21, 2009
Interventional
Conditions
Summary
Pain from damaged nerves is a common problem particularly in the aged and those with medical problems including diabetes, vascular disease and cancer.A medication called ketamine which is used for anaesthetics is, at much lower doses, also used to help try and control severe chronic nerve pain. In an experiment that has been carried out at Flinders University in the laboratory, it appears that ketamine may increase the effective blood levels of opioid pain killers such as codeine or morphine that are often given in conjunction with ketamine. This study will evaluate whether increased codeine levels are seen when both codeine and ketamine are administered in small doses to well volunteers.Ketamine is already being evaluated in a clinical study by a team led by Flinders University at eight sites across Australia for severe nerve-based pain. This study will be a definitive study on the place of ketamine in the control of chronic, complex pain and should be finished in mid-2010.This study will have huge importance if ketamine is shown to be of clinical benefit. To date, it may well be that the perceived clinical benefit is only because of its effect on increasing the blood levels of strong pain killers.
Eligibility
Inclusion Criteria1
- Participant is capable of completing all participant assessments and complying with the study procedures, is able to give fully informed written consent, Normal performance status = Australian-modified Karnofsky performance stauts of 100.
Exclusion Criteria1
- Any history of drug or alcohol abuse, any known allergy to either of the study medications,alcohol consumption during the trial period, on any regular or as needed medications including opioids and Non Steroidal Anti Inflammatory Drugs(NSAIDs),anaemia, renal dysfunction with creatinine clearance calculated as less than 25 ml/minute. Hepatic impairment defined as 2 times upper limit of mormal for 2 or more hepatic enzymes, International normalized ratio (INR >1.2 )– not treated with warfarin, documented respiratory failure induced by any opiate medication,recent seizures or history of uncontrolled epilepsy, medically assessed history of uncontrolled hypertension, cardiac arrhythmias, cardiac failure, ischaemic heart disease or history of cerebral vascular accident, cerebral trauma, intracerebral mass or previous intracerebral haemorrhage, currently taking monoamine oxidase inhibitors (MAOIs) or who have been taking non-reversible monoamine oxidase inhibitors within 4 weeks prior to study entry or reversible MAOIs within 5 days of study entry, history of increased intraocular pressure (e.g. glaucoma), schizophrenia, acute psychosis, acute intermittent porphyria, uncontrolled hyperthyroidism,women pregnant or lactating and if at risk of pregnancy must have appropriate and effective contraception in place.
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Interventions
Study exposure is for 4 days and commences with a comprehensive medical assessment to identify that the participants meet the eligibility criteria.Participants will take in total 9 doses of 30mg of codeine orally every 8 hours. The first 5 doses will be taken at home, ie days 1 and 2 of the study. On day 3 the participants will continue to take the codeine 30mg every 8 hours orally but will be monitored in hospital from 08.00 to 16.00. 11 samples of blood will be taken at predetermined times throughout the day and at the same time vital signs, pulse, respirations and blood pressure, will be measured by a registered nurse. On day 4 the participant will again be monitored in hospital from 08.00 hours to 16.00 hours. The final dose of codeine 30mg orally will be given at 08.00 hours and at the same time ketamine 0.5mg per kg of body weight up to a maximum of 40mg will be given intravenously over 5 minutes. Again 11 blood samples will be taken at predetermined times throughout the day, and vital signs , pulse, respirations and blood pressure will be measured at the same time. An intravenous cannual, a small plastic tube, will be inserted into a vein in the arm on both days 3 and 4 which will be used to collect the 11 blood samples on each day, thus eliminating the need to insert a needle into the vein each time a blood sample is required. On both days 3 and 4, whilst in hospital, all urine passed by the participants will be collected.
Locations(1)
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ACTRN12610000283077