Stereoselective pharmacokinetics of ketamine and norketamine after constant rate infusion of a subanesthetic dose of racemic ketamine or S-ketamine in Shetland ponies

Abstract

CRI of S-ketamine may be preferable over CRI of racemic ketamine in standing equids because the S-enantiomer was eliminated faster when infused alone instead of as part of a racemic mixture.

Stereoselective determination of drugs and metabolites in body fluids, tissues and microsomal preparations by capillary electrophoresis (2000–2010)

“…Other investigations dealt with the complete elucidation of the pharmacokinetics via analysis of the drug enantiomers in plasma or serum. Examples studied included the drugs anisodamine [75], carvedilol [78], ibafloxacine [81], ibuprofen [82,83], indobufen [84], ketoprofen [85], trans-tramadol [91,93], venlafaxine [94] and ketamine [157,160,161,163]. For one drug, carvedilol, enantiomer plasma concentrations were found to be comparable to those determined by HPLC [78].…”

“…Compared to the previous decade, during which mostly uncharched CDs were employed [26], we noted a strong increase of the use of charged CDs. S-␤-CD, with 7-11 mol sulfate/mol ␤-CD, was most often used [58,60,63,69,71,79,80,83,95,97,99,101,108,110,118,123,131,134,135,139,[154][155][156][157][158][159][160][161][162][163][164][165][166][167][168][169] whereas the better defined highly sulfated CD derivatives (HS-␤-CD and HS-␥-CD [170]) were only used in a few assays [50,51,72,111,144,145]. These and other selectors, such as phosphated-␥-CD (PH-␥-CD) [94,106,126], carboxymethyl-␤-CD (CM-␤-CD) or carboxymethyl-␥-CD (CM-␥-CD) …”

“…bolus drug administration under isoflurane anesthesia [160] rac-K, S-K NK Pony plasma Pharmacokinetics after single i.v. bolus drug administration and sedation with xylazine [161] rac-K, S-K NK Pony plasma Effects of low-dose infusion on nociceptive withdrawal reflex in standing ponies [162] rac-K, S-K NK Pony plasma Pharmacokinetics after constant rate, low dose (subanesthetic) infusion in ponies [163] rac-K, S-K NK Horse plasma Anesthesia recovery quality after low-dose infusion during anesthesia with isoflurane [164] rac-K NK Canine plasma Effect on nociceptive stimuli after low-dose constant rate infusion in concious dogs [165] rac-K, S-K NK Equine liver and lung microsomes…”

“…As with our previous compilation 10 years ago [26], insight into the achievements is presented via distinction between enantiomer analysis in fortified body fluids (Table 1), body fluids and tissues of humans and animals (Tables 2 and 3), in vitro preparations (Table 4) and in forensic biosamples (Table 5 [ ). Furthermore, the stereoselective CE work associated with a multidisciplinary ketamine project is presented separately (Table 6 [ [154][155][156][157][158][159][160][161][162][163][164][165][166][167][168][169]). Major focus is given on systems in which stereoisomers of parent drug and metabolites are analyzed together in one run.…”

Chiral electromigration techniques in pharmaceutical and biomedical analysis

“…Thormann and colleagues have extensively studied the in vitro and in vivo metabolism of the anesthetic drug ketamine in equine plasma [129,130], dog plasma [131], equine, canine and human liver microsomes [132,133] and single human CYP isoenzymes [134]. The drug undergoes hepatic first-pass metabolism, the major pathways include N-demethylation to norketamine followed by hydroxylation and further glucuronidation or formation of 5,6-dehydronorketamine.…”