Ketamine Disposition in Children and Adults

Abstract

The pharmacokinetics of ketamine 2 mg kg-1 i.v. and 6 mg kg-1 i.m. were investigated in nine children undergoing minor surgery. After either route of administration plasma ketamine concentrations were similar to those found in adult patients receiving the same dose, except at later times after i.v. injection, when concentrations were smaller in children. Also, absorption after i.m. injection appeared to be more rapid in children. Substantially larger concentrations of the metabolite norketamine were found in children than in adults after the injection of ketamine. Concentrations of ketamine upon awakening in a further group of nine children receiving ketamine as the sole anaesthetic showed large inter-individual variation. The concentrations were greater than those previously reported for adults. The greater dose requirements in children, compared with adults, are probably attributable to pharmacodynamic rather than pharmacokinetic factors.

Cytoskeleton Interruption in Human Hepatoma HepG2 Cells Induced by Ketamine Occurs Possibly through Suppression of Calcium Mobilization and Mitochondrial Function

“…Administration of neither 25, 50, nor 100 M ketamine was cytotoxic to HepG2 cells. Concentrations of ketamine used in this study are within the range of clinical relevance (Domino et al, 1982;Grant et al, 1983). Under such clinically relevant concentrations, ketamine suppressed polymerization of F-actin and microtubular cytoskeletons.…”

“…Ketamine was dissolved in phosphate-buffered saline (0.14 M NaCl, 2.6 mM KCl, 8 mM Na 2 HPO 4 , and 1.5 mM KH 2 PO 4 ). Concentrations of ketamine (Յ100 M), which correspond to clinical plasma concentrations (Domino et al, 1982;Grant et al, 1983), were chosen as the treated dosages in this study. To avoid drug interaction, when HepG2 cells were exposed to ketamine, the culture medium did not contain serum and antibiotics.…”

Unconventional ligands and modulators of nicotinic receptors

“…However, the findings that the concentrations at which ketamine inhibits the NMDA receptors are about 10-fold lower than the plasma concentrations needed to induce anesthesia in mammals have suggested that inhibition of NMDA receptors may not be the only determinant of dissociative anesthesia (Grant et al, 1983;Coan and Collingridge, 1987). Studies investigating the sensitivity of numerous ligand-gated channels ectopically expressed in different systems to these compounds came to demonstrate that ␣7 nAChRs as well as ␤4* and ␤2* nAChRs can be inhibited noncompetitively and voltage dependently by ketamine and MK-801 (Ramoa et al, 1990;Buisson and Bertrand, 1998;Furuya et al, 1999).…”

Long term high dose morphine, ketamine and midazolam infusion in a child with burns.

“…No psychological sequelae were observed in our patient, possibly because of the co-administration of midazolam (Park et al, 1987). Grant et al (1983) reported a greater plasma clearance of ketamine in children aged 4-9 years than in adults (16.8 and 12.6 ml min-' kg-', respectively). They also found greater plasma norketamine concentrations in children than in adults suggesting that the N-demethylation of ketamine to norketamine is the major metabolic pathway in children.…”

“…Its major metabolite is norketamine which animal studies suggest is pharmacologically active (White et al, 1982). There have been few studies of the pharmacokinetics of ketamine in children (Cook et al, 1982;Grant et al, 1983). It is well known that thermal injury causes 'resistance' to many drugs used in anaesthetic practice (Marathe et al, 1989;Martyn, 1986;White et al, 1982) Total parenteral nutrition (glucose, aminoacids and fat) and albumin were given from day 2 (see Figure 1).…”