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BIOAVAILABILITY OF KETAMINE AFTER ORAL OR SUBLINGUAL ADMINISTRATION

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CC Chong, SA Schug, M Page-Sharp, KF Ilett
Dept of Anaesthesia and Pain, Royal Perth Hospital, Perth, WA

Aim

To describe the bioavailability of ketamine after oral or sublingual administration.

Method

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 (AUC0-8h) (TopFit Ver 2.0). Bioavailability was calculated as AUC0-8h/doseoral or sublingual x 100/AUC0-8h/dosei.v.. Group data were compared using a paired t-test (SigmaStat Ver 2.0).

Result

The mean ± SD pharmacokinetic parameters are summarised in the Table.

Parameter	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 (µg.h/l.mg)	13.4 ± 2.4	4.0 ± 1.9	3.1 ± 0.7	13.0 ± 6.9	9.9 ± 5.3	12.1 ± 5.3

The bioavailabilies (mean ± SD) of ketamine after sublingual and oral administration were 32 ± 17% and 23 ± 9% respectively. When the contribution from norketamine (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 ketamine1, further studies are needed to determine analgesic efficacy of sublingual versus oral ketamine.

This project was funded by an ANZCA Research Grant

Time of Presentation
Saturday 13 May 2006 - 1530-1700

References

1.Bjarke E, Mikkelsen S, Thorkildsen C, Borgbjerg F. European Journal of Pharmacology 1997; 333:99-104.

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