We have studied the pharmacokinetics and distribution of ketamine and its biotransformation products in dogs after extradural administration of ketamine at L4-5. The mean apparent uptake rate constants of ketamine for plasma and CSF were 4.17 (SD 1.84) and 5.15 (2.50) h-1, respectively. The concentrations of ketamine in CSF were greater than those found in plasma. The elimination half-life values of the parent drug for both biological fluids were similar (4.3 (2.96) h and 4.6 (3.31) h for plasma and CSF, respectively). The apparent formation rate constant of norketamine was greater than that of dehydronorketamine. However, the concentrations of the biotransformation products in CSF were smaller than those of the parent drug. These results are similar to the distribution of ketamine and its metabolites in different cerebral structures and tissues. The concentrations decreased in concert with the increase in polarity of the metabolites. A specific distribution for all compounds was observed. Ketamine showed a greater affinity for brainstem, while norketamine and dehydronorketamine were distributed mostly in cerebellum and kidney, respectively.

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We have studied the pharmacokinetics of ketamine administered rectally in a dose of 10 mg kg-1 to five children aged 6-9 yr and mean weight 28.80 (SD 6.55) kg. An acceptable level of anaesthesia was not obtained in any patient. Despite this, the degree of analgesia obtained was good and no child required further administration of analgesics during the postoperative period. Tolerance to the suppositories was excellent. The absorption of ketamine was found to be relatively fast, with a median peak concentration of 160 ng ml-1 (range 96-250 ng ml-1) at 0.75 h (range 0.50-1.00 h) after administration. The plasma concentrations of norketamine were greater than those of the parent drug, with a maximum of 510 ng ml-1 (range 450-810 ng ml-1) at 0.81 h (range 0.50-1.00 h) after administration. The medians of the half-lives of ketamine and norketamine were 3.15 h and 2.56 h, respectively (range 1.57-4.95 h and 1.47-5.30 h, respectively).

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The present study was carried out to define the pharmacokinetics of salbutamol sulfate administered to mongrel dogs in five pharmaceutical forms via two routes of administration. One pharmaceutical form was administered intravenously (Ventolin i.v.) while the other four were administered orally (Ventolin: immediate-release formulation, Volmax: commercial osmotic pump, SG7 and SG14: sustained-release hydrophilic matrices developed in our laboratory). We obtained a first-order release kinetic of the salbutamol from Ventolin and SG7, whereas a zero-order release kinetic was observed for SG14 and Volmax formulations. Oral bioavailability was 80% and there were neither significant differences (P > 0.05) in terms of the calculation method used (relation of the areas under the plasma level curve Loo-Riegelman, deconvolution) nor in terms of the dosage form (Ventolin Volmax, SG7 and SG14). The elimination half-life value of salbutamol was 1.2 h when administered intravenously; this parameter had a value of 3.0 h for the immediate-release formulation and ranged between 5.4 and 7.2 h in the sustained-release formulations when administered orally. These changes in the half-life value of the sustained-release formulations will allow us to modify the frequency of administration in relation to immediate-release formulations.