Exponente alomérico dependiente del peso corporal para escalar la eliminación a través de la duración de la vida humana
A bodyweight-dependent allometric exponent for scaling clearance across the human life-span.
Wang C, Peeters MY, Allegaert K, Blussé van Oud-Alblas HJ, Krekels EH, Tibboel D, Danhof M, Knibbe CA.
Division of Pharmacology, LACDR, Leiden University, Leiden, the Netherlands.
Pharm Res. 2012 Jun;29(6):1570-81. doi: 10.1007/s11095-012-0668-x.
Abstract
PURPOSE:To explore different allometric equations for scaling clearance across the human life-span using propofol as a model drug. METHODS: Data from seven previously published propofol studies ((pre)term neonates, infants, toddlers, children, adolescents and adults) were analysed using NONMEM VI. To scale clearance, a bodyweight-based exponential equation with four different structures for the exponent was used: (I) 3/4 allometric scaling model; (II) mixture model; (III) bodyweight-cut-point separated model; (IV) bodyweight-dependent exponent model. RESULTS: Model I adequately described clearance in adults and older children, but overestimated clearance of neonates and underestimated clearance of infants. Use of two different exponents in Model II and Model III showed significantly improved performance, but yielded ambiguities on the boundaries of the two subpopulations. This discontinuity was overcome in Model IV, in which the exponent changed sigmoidally from 1.35 at a hypothetical bodyweight of 0 kg to a value of 0.56 from 10 kg onwards, thereby describing clearance of all individuals best. CONCLUSIONS: A model was developed for scaling clearance over the entire human life-span with a single continuous equation, in which the exponent of the bodyweight-based exponential equation varied with bodyweight.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3349030/pdf/11095_2012_Article_668.pdf
Propofol en emulsión lipídica atenúa menos la regulación de la temperatura corporal que la microemulsión de propofol o el sevoflurano en los ancianos.
Lipid-emulsion propofol less attenuates the regulation of body temperature than micro-emulsion propofol or sevoflurane in the elderly.
Jeong CW, Ju J, Lee DW, Lee SH, Yoon MH.
Department of Anesthesiology and Pain Medicine, Chonnam National University Medical School, Gwangju, Korea.
Yonsei Med J. 2012 Jan;53(1):198-203. doi: 10.3349/ymj.2012.53.1.198.
Abstract
PURPOSE: Anesthesia and surgery commonly cause hypothermia, and this caused by a combination of anesthetic-induced impairment of thermoregulatory control, a cold operation room environment and other factors that promote heat loss. All the general anesthetics markedly impair normal autonomic thermoregulatory control. The aim of this study is to evaluate the effect of two different types of propofol versus inhalation anesthetic on the body temperature. MATERIALS AND METHODS: In this randomized controlled study, 36 patients scheduled for elective laparoscopic gastrectomy were allocated into three groups; group S (sevoflurane, n=12), group L (lipid-emulsion propofol, n=12) and group M (micro-emulsion propofol, n=12). Anesthesia was maintained with typical doses of the study drugs and all the groups received continuous remifentanil infusion. The body temperature was continuously monitored after the induction of general anesthesia until the end of surgery. RESULTS: The body temperature was decreased in all the groups. The temperature gradient of each group (group S, group L and group M) at 180 minutes from induction of anesthesia was 2.5 ± 0.6°C, 1.6 ± 0.5°C and 2.3 ± 0.6°C, respectively. The body temperature of group L was significantly higher than that of group S and group M at 30 minutes and 75 minute after induction of anesthesia, respectively. There were no temperature differences between group S and group M. CONCLUSION: The body temperature is maintained at a higher level in elderly patients anesthetized with lipid-emulsion propofol.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3250313/pdf/ymj-53-198.pdf
Mecanismo GABAergico de la toxicidad de propofol en neuronas inmaduras
GABAergic mechanism of propofol toxicity in immature neurons.
Kahraman S, Zup SL, McCarthy MM, Fiskum G.
Department of Anesthesiology, University of Maryland, Baltimore, MD 21201, USA.
J Neurosurg Anesthesiol. 2008 Oct;20(4):233-40. doi: 10.1097/ANA.0b013e31817ec34d.
Abstract
Certain anesthetics exhibit neurotoxicity in the brains of immature but not mature animals. Gamma-aminobutyric acid (GABA), the primary inhibitory neurotransmitter in the adult brain, is excitatory on immature neurons via its action at the GABAA receptor, due to a reversed transmembrane chloride gradient. GABAA receptor activation in immature neurons is sufficient to open L-type voltage-gated calcium channels. As propofol is a GABAA agonist, we hypothesized that it and more specific GABAA modulators would increase intracellular free calcium ([Ca2+]i), resulting in the death of neonatal rat hippocampal neurons. Neuronal [Ca2+]i was monitored using Fura2-AM fluorescence imaging. Cell death was assessed by double staining with propidium iodide and Hoechst 33258 at 1 hour (acute) and 48 hours (delayed) after 5 hours exposure of neurons to propofol or the GABAA receptor agonist, muscimol, in the presence and absence of the GABA receptor antagonist, bicuculline, or the L-type Ca2+ channel blocker, nifedipine. Fluorescent measurements of caspase-3,-7 activities were performed at 1 hour after exposure. Both muscimol and propofol induced a rapid increase in [Ca2+]i in days in vitro (DIV) 4, but not in DIV 8 neurons, that was inhibited by nifedipine and bicuculline. Caspase-3,-7 activities and cell death increased significantly in DIV 4 but not DIV 8 hippocampal neuronal cultures 1 hour after 5 hours exposure to propofol, but not muscimol, and were inhibited by the presence of bicuculline or nifedipine. We conclude that an increase in [Ca2+]i, due to activation of GABAA receptors and opening of L-type calcium channels, is necessary for propofol-induced death of immature rat hippocampal neurons but that additional mechanisms not elicited by GABAA activation alone also contribute to cell death.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2730603/pdf/nihms107690.pdf
Atentamente
Anestesiología y Medicina del Dolor
www.anestesia-dolor.org
A bodyweight-dependent allometric exponent for scaling clearance across the human life-span.
Wang C, Peeters MY, Allegaert K, Blussé van Oud-Alblas HJ, Krekels EH, Tibboel D, Danhof M, Knibbe CA.
Division of Pharmacology, LACDR, Leiden University, Leiden, the Netherlands.
Pharm Res. 2012 Jun;29(6):1570-81. doi: 10.1007/s11095-012-0668-x.
Abstract
PURPOSE:To explore different allometric equations for scaling clearance across the human life-span using propofol as a model drug. METHODS: Data from seven previously published propofol studies ((pre)term neonates, infants, toddlers, children, adolescents and adults) were analysed using NONMEM VI. To scale clearance, a bodyweight-based exponential equation with four different structures for the exponent was used: (I) 3/4 allometric scaling model; (II) mixture model; (III) bodyweight-cut-point separated model; (IV) bodyweight-dependent exponent model. RESULTS: Model I adequately described clearance in adults and older children, but overestimated clearance of neonates and underestimated clearance of infants. Use of two different exponents in Model II and Model III showed significantly improved performance, but yielded ambiguities on the boundaries of the two subpopulations. This discontinuity was overcome in Model IV, in which the exponent changed sigmoidally from 1.35 at a hypothetical bodyweight of 0 kg to a value of 0.56 from 10 kg onwards, thereby describing clearance of all individuals best. CONCLUSIONS: A model was developed for scaling clearance over the entire human life-span with a single continuous equation, in which the exponent of the bodyweight-based exponential equation varied with bodyweight.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3349030/pdf/11095_2012_Article_668.pdf
Propofol en emulsión lipídica atenúa menos la regulación de la temperatura corporal que la microemulsión de propofol o el sevoflurano en los ancianos.
Lipid-emulsion propofol less attenuates the regulation of body temperature than micro-emulsion propofol or sevoflurane in the elderly.
Jeong CW, Ju J, Lee DW, Lee SH, Yoon MH.
Department of Anesthesiology and Pain Medicine, Chonnam National University Medical School, Gwangju, Korea.
Yonsei Med J. 2012 Jan;53(1):198-203. doi: 10.3349/ymj.2012.53.1.198.
Abstract
PURPOSE: Anesthesia and surgery commonly cause hypothermia, and this caused by a combination of anesthetic-induced impairment of thermoregulatory control, a cold operation room environment and other factors that promote heat loss. All the general anesthetics markedly impair normal autonomic thermoregulatory control. The aim of this study is to evaluate the effect of two different types of propofol versus inhalation anesthetic on the body temperature. MATERIALS AND METHODS: In this randomized controlled study, 36 patients scheduled for elective laparoscopic gastrectomy were allocated into three groups; group S (sevoflurane, n=12), group L (lipid-emulsion propofol, n=12) and group M (micro-emulsion propofol, n=12). Anesthesia was maintained with typical doses of the study drugs and all the groups received continuous remifentanil infusion. The body temperature was continuously monitored after the induction of general anesthesia until the end of surgery. RESULTS: The body temperature was decreased in all the groups. The temperature gradient of each group (group S, group L and group M) at 180 minutes from induction of anesthesia was 2.5 ± 0.6°C, 1.6 ± 0.5°C and 2.3 ± 0.6°C, respectively. The body temperature of group L was significantly higher than that of group S and group M at 30 minutes and 75 minute after induction of anesthesia, respectively. There were no temperature differences between group S and group M. CONCLUSION: The body temperature is maintained at a higher level in elderly patients anesthetized with lipid-emulsion propofol.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3250313/pdf/ymj-53-198.pdf
Mecanismo GABAergico de la toxicidad de propofol en neuronas inmaduras
GABAergic mechanism of propofol toxicity in immature neurons.
Kahraman S, Zup SL, McCarthy MM, Fiskum G.
Department of Anesthesiology, University of Maryland, Baltimore, MD 21201, USA.
J Neurosurg Anesthesiol. 2008 Oct;20(4):233-40. doi: 10.1097/ANA.0b013e31817ec34d.
Abstract
Certain anesthetics exhibit neurotoxicity in the brains of immature but not mature animals. Gamma-aminobutyric acid (GABA), the primary inhibitory neurotransmitter in the adult brain, is excitatory on immature neurons via its action at the GABAA receptor, due to a reversed transmembrane chloride gradient. GABAA receptor activation in immature neurons is sufficient to open L-type voltage-gated calcium channels. As propofol is a GABAA agonist, we hypothesized that it and more specific GABAA modulators would increase intracellular free calcium ([Ca2+]i), resulting in the death of neonatal rat hippocampal neurons. Neuronal [Ca2+]i was monitored using Fura2-AM fluorescence imaging. Cell death was assessed by double staining with propidium iodide and Hoechst 33258 at 1 hour (acute) and 48 hours (delayed) after 5 hours exposure of neurons to propofol or the GABAA receptor agonist, muscimol, in the presence and absence of the GABA receptor antagonist, bicuculline, or the L-type Ca2+ channel blocker, nifedipine. Fluorescent measurements of caspase-3,-7 activities were performed at 1 hour after exposure. Both muscimol and propofol induced a rapid increase in [Ca2+]i in days in vitro (DIV) 4, but not in DIV 8 neurons, that was inhibited by nifedipine and bicuculline. Caspase-3,-7 activities and cell death increased significantly in DIV 4 but not DIV 8 hippocampal neuronal cultures 1 hour after 5 hours exposure to propofol, but not muscimol, and were inhibited by the presence of bicuculline or nifedipine. We conclude that an increase in [Ca2+]i, due to activation of GABAA receptors and opening of L-type calcium channels, is necessary for propofol-induced death of immature rat hippocampal neurons but that additional mechanisms not elicited by GABAA activation alone also contribute to cell death.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2730603/pdf/nihms107690.pdf
Atentamente
Anestesiología y Medicina del Dolor
www.anestesia-dolor.org
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