Pharmacokinetics of Propofol in Children

Abstract

The pharmacokinetics of propofol were studied in 12 healthy Chinese children, aged 4-12 yr, undergoing circumcision under inhalation anaesthesia. All patients received a single i.v. bolus dose of propofol 2.5 mg kg-1 and blood concentrations of propofol over the subsequent 24 h were measured using high pressure liquid chromatography with fluorimetric detection. Data were consistent with a three-compartment model with a mean (SEM) elimination half-life of 209 (29) min and total body clearance of 40.4 (3.6) ml min-1 kg-1. The mean (SEM) apparent volume of distribution at steady state was 5.0 (2.7) litre kg-1 and volume of the central compartment was 0.6 (0.1) litre kg-1. The mean (SEM) ratio of k12:k21 was 1.4 (0.2), suggesting that, after injection of a single bolus dose in children, propofol is distributed rapidly to the shallow compartment. The mean ratio of k31:k10 suggests that lipophilicity constrains return of the drug to the central compartment.

Propofol decreases cerebral blood flow velocity in anesthetized children

“…11 The propofol dosing regimen used in the present study was adapted from published pharmacokinetic studies of propofol infusion data in children. [12][13][14][15] For the "low" propofol concentration arm of the study, a manual infusion regimen capable of maintaining an estimated steady state blood concentration of 3 µg·mL -1 in children was used. 8 This same target concentration has been chosen in several adult studies.…”

“…19 Due to significant pharmacokinetic and pharmacodynamic differences between children and adults however, propofol doses and infusion rates required to achieve a certain target blood concentration are higher for pediatric patients. 13,16 In addition, the context-sensitive half-life of propofol is longer in children than in adults, presumably due to altered compartment volumes of distribution. 8 This implies that recovery from a propofol infusion will be slower in children than in adults, which may limit its usefulness in prolonged neurosurgical procedures.…”

Método simplificado para manutenção da concentração sangüínea de propofol em nível aproximadamente constante, associado ao óxido nitroso no paciente pediátrico

“…Na criança, as curvas de concentrações do propofol são melhor descritas pelo modelo tricompartimental, com uma meia-vida inicial curta (1,5 a 4,2 minutos), pela ocorrência da redistribuição que é seguida por uma segunda fase (9,3 a 56 minutos) associada à alta depuração metabólica no fígado e em outros locais de grande volume de distribuição. Finalmente, a terceira fase final (209 a 475 minutos) reflete o período de eliminação lenta dos tecidos pouco vascularizados 21,22 . Desse modo, na criança, o volume de distribuição do compartimento central (343 ml.kg -1 ) é maior quando comparado ao do adulto (228 ml.kg -1 ).…”

“…Propofol concentration curves in children are better described by a tricomparmental model, with a short initial half-life (1.5 to 4.2 minutes), due to redistribution process, followed by a second phase (9.3 to 56 minutes) associated to high metabolic clearance in the liver and in other large distribution volume sites. The third and final phase (209 to 475 minutes) reflects the slow elimination process of less vascularized tissues 21,22 . So, in children, central compartment distribution volume (343 ml.kg -1 ) is higher as compared to adults (228 ml.kg -1 ).…”

Analgesia e sedação em situações de emergência e unidades de tratamento intensivo pediátrico

“…Its half-life decreases with age, probably due to better metabolism and increase in the liver blood flow. 21 It has the added advantage of providing rapid sedation. Propofol has been safely used in short-term sedation before painful procedures such as lumbar puncture and cardioversion in patients on spontaneous ventilation.…”