S-ketamine and s-norketamine plasma concentrations after nasal and i.v. administration in anesthetized children.
BACKGROUND
It has been suggested that nasal administration of s-ketamine may be used to improve sedation or premedication in combination with nasal midazolam in pediatric patients. In this study we measured and compared plasma concentrations of s-ketamine and its main metabolite s-norketamine after nasal and i.v. administration in preschool children.


METHODS
During sevoflurane anaesthesia, 20 children, aged 1-7 years, weight 11-25 kg, received s-ketamine 2 mg x kg(-1) either intranasally (Group IN, n = 10), or i.v. (Group IV, n = 10). Six venous blood samples were obtained up to 60 min after drug administration for measurement of s-ketamine and s-norketamine plasma concentrations.


RESULTS
Plasma concentrations [mean +/- sd] of s-ketamine in group IN peaked at 355 +/- 172 ng x ml(-1) within 18 +/- 13 min vs. 1860 +/- 883 ng x ml(-1) within 3 +/- 1 min in group IV (P < 0.01). Plasma concentrations of s-norketamine in group IN peaked at 90 +/- 128 ng x ml(-1) within 50 +/- 11 min vs. 429 +/- 277 ng x ml(-1) within 40 +/- 16 min in group IV (P < 0.01). One child in group IN experienced rapid and high level s-ketamine absorption with a peak plasma concentration of 732 ng x ml(-1) after 2 min, which decreased to 274 ng x ml(-1) after 60 min. Systolic blood pressure and heart rate remained unaltered in both study groups after s-ketamine administration.


CONCLUSIONS
Nasal administration of s-ketamine 2 mg x kg(-1) results in a wide spread of plasma concentrations and absorption times. Rapid and high level drug absorption after nasal drug administration is possible. The use of a pulse oximeter and continuous observation after nasal administration of s-ketamine for pediatric premedication is recommended.
Weber
Frank
F
Department of Anaesthesia, University of Regensburg, Regensburg, Germany. frank.weber@klinik.uni-regensburg.de
Wulf
Hinnerk
H
Gruber
Michael
M
Biallas
Ralf
R
D000281:Administration, Intranasal; D000700:Analgesics / Q000008:administration & dosage* / Q000097:blood* / Q000493:pharmacokinetics; D000704:Analysis of Variance; D002648:Child; D002675:Child, Preschool; D006801:Humans; D007223:Infant; D007275:Injections, Intravenous; D007649:Ketamine / Q000008:administration & dosage* / Q000031:analogs & derivatives* / Q000097:blood* / Q000493:pharmacokinetics; D011446:Prospective Studies; D013997:Time Factors
D000700:Analgesics; D007649:Ketamine; C033419:norketamine