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Population pharmaco...
Population pharmacokinetics of S-ketamine and norketamine in healthy volunteers after intravenous and oral dosing
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- Fanta, Samuel (författare)
- Uppsala universitet,Institutionen för farmaceutisk biovetenskap
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Kinnunen, Mari (författare)
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Backman, Janne T. (författare)
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Kalso, Eija (författare)
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(creator_code:org_t)
- 2015-03-01
- 2015
- Engelska.
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Ingår i: European Journal of Clinical Pharmacology. - : Springer Science and Business Media LLC. - 0031-6970 .- 1432-1041. ; 71:4, s. 441-447
- Relaterad länk:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- Low-dose ketamine is a lucrative therapeutic approach in cancer pain, perioperative treatment of pain, and management of treatment-resistant depression. The analgesic potency of its main metabolite norketamine is thought to be one third that of ketamine. However, few studies exist on the pharmacokinetics of orally administered S-ketamine. In our study, 11 healthy volunteers received S-ketamine 0.25 mg/kg orally and 0.125 mg/kg intravenously. S-ketamine and norketamine concentrations were measured up to 23.5 h post-dose. A population pharmacokinetic model was built to describe S-ketamine and norketamine pharmacokinetics. A three-compartment model for both S-ketamine and norketamine best described the data. To accommodate for the extensive formation of norketamine after oral S-ketamine, a separate presystemic absorption-phase component was included in addition to its systemic formation. The oral bioavailability of S-ketamine was low, 8 % (11 % interindividual variability), and its clearance was high, 95 L/h/70 kg (13 % interindividual variability). Simulations suggested that after oral dosing, norketamine AUC at steady state is 16.5 times higher than that of S-ketamine. Given that the analgesic effect of S-ketamine is due to both S-ketamine and norketamine, relatively small oral doses of S-ketamine can be assumed to be a feasible alternative to repeated intravenous dosing, for example in the setting of chronic pain.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Farmaceutiska vetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Pharmaceutical Sciences (hsv//eng)
Nyckelord
- Ketamine
- S-ketamine
- Norketamine
- Population pharmacokinetics
- CYP2B6
- CYP3A4
- First-pass effect
- Well-stirred model
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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