Bioavailability of Ketamine After Oral or Sublingual Administration:

Abstract

Aim: To describe the bioavailability of ketamine after oral or sublingual administration. Methods: This was a randomised cross-over study (10 mg intravenously (i.v.) and 25 mg sublingually or orally) involving six inpatients with neuropathic pain. Written informed consent was obtained. Serial blood samples were taken for drug analysis over an 8 hour period starting just before dose administration. Ketamine and norketamine in plasma were analysed using high performance liquid chromatography. The concentration-time profiles were subjected to noncompartmental analysis, including measurement of the area under the concentration-time curve (AUC 0-8 h) (TopFit Ver 2.0). Bioavailability was calculated as AUC 0-8 h /dose oral or sublingual × 100/AUC 0-8 h /dose i.v.. Group data were compared using a paired t-test (SigmaStat Ver 2.0). Results: The mean ± SD pharmacokinetic parameters are summarised in the Table. Ketamine Norketamine Parameter i.v. Sublingual Oral i.v. Sublingual Oral Cmax (µg/l) 156 ± 161 28.6 ± 6.6 22.8 ± 12.8 38 ± 29 66 ± 29 82 ± 34 Tmax (h) 0.24 ± 0.29 0.76 ± 0.51 0.96 ± 0.8 0.6 ± 0.7 1.9 ± 1.0 1.6 ± 0.9 AUC/dose 13.4 ± 2.4 4.0 ± 1.9 3.1 ± 0.7 13.0 ± 6.9 9.9 ± 5.3 12.1 ± 5.3 (µg.h/l.mg) The bioavailabilies (mean ± SD) of ketamine after sub-lingual and oral administration were 32 ± 17% and 23 ± 9% respectively. When the contribution from norketa-mine (as ketamine equivalents) was also included, the combined bioavailabilities increased to 54 ± 17% and 59 ± 16% respectively. Conclusion: Both the bioavailability of ketamine alone, and when combined with norketamine was similar after sublingual or oral administration. However, norketamine made a substantial contribution to AUC and the combined bioavailability after both routes. Since norketamine may contribute to analgesic effect of oral ketamine 1 , further studies are needed to determine analgesic efficacy of sublingual versus oral ketamine. The availability of medical information is now spread over several frequently used media. This includes printed journals, on-line journals, text books, conferences, DVD's, audio tapes / CD's, formal and informal discussions (with friends and colleagues), and sometimes newspaper articles and TV presentations. The practice of evidence-based medicine encourages medical practitioners to utilise a selection of these resources, assimilate the information, and condense it into clinical pathways or protocols that can be applied consistently to patient management. The Pub Med database alone has 6.6 million references including 0.7 million reviews [Limits "Human / English"]. "Where is the evidence?" is asked by ourselves, administrators , clinicians, allied medical staff, and occasionally by patients. It is also asked by lawyers and insurance clerks. Individual practitioners try to answer this question when asked. The frequent answer is "Where did I put that article?" Purpose of the Study: Can exposure to a novel idea increase the frequency of medical searches to answer clinical questions? Are the number of references stored increased? Is reference retrieval enhanced? Method: A questionnaire was used to assess the historical frequency of medical searches, and the method used to store and retrieve references. After exposure to the program, the number of references stored (to the database) was calculated, and the frequency of searches made by each user (and reference retrieval). Results: In the early assessment phase users had access to the program for an average of 16 days. This resulted in an average of 8 references stored per user. However, 50% of users were responsible for 91% of the references stored. Conclusions: It is possible that a novel idea which helps to minimise the effort (and time) taken by individuals to do searches, which also stores and retrieves references, may help practitioners seeking to use an "evidence based medicine" approach.