RESUMO
We determined the pharmacokinetics and duration of action of a bolus dose of doxacurium (15 micrograms/kg) in 27 patients anesthetized with isoflurane and nitrous oxide. Nine patients had normal renal and liver functions and were undergoing a variety of surgical procedures, nine were undergoing cadaveric kidney transplantation because of end-stage renal disease, and nine were undergoing cadaveric liver transplantation because of end-stage hepatocellular disease. Plasma concentrations of doxacurium were measured for 6 h after administration using a sensitive and specific capillary gas chromatographic assay. Plasma concentration versus time data were analyzed by a noncompartmental method based on statistical moments. Neuromuscular blockade was assessed by measuring the electromyographic evoked response of the adductor pollicis muscle to train-of-four stimulation of the ulnar nerve. The degree of neuromuscular blockade after doxacurium administration was described as the percent of control of the first train-of-four response. The pharmacokinetic variables were (normal vs hepatic failure vs renal failure, respectively): volume of distribution at steady state (220 +/- 110 vs 290 +/- 60 vs 270 +/- 130 mL/kg [mean +/- SD]), plasma clearance (2.7 +/- 1.6 vs 2.3 +/- 0.4 vs 1.2 +/- 0.7 mL.kg-1.min-1), mean residence time (95.2 +/- 57 vs 129.4 +/- 30 vs 270 +/- 210 min), and elimination half-life (99 +/- 54 vs 115 +/- 31 vs 221 +/- 156 min). Plasma clearance and mean residence time differed significantly between patients with renal failure and control patients.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Isoquinolinas/farmacocinética , Falência Renal Crônica/metabolismo , Hepatopatias/metabolismo , Fármacos Neuromusculares não Despolarizantes/farmacocinética , Adulto , Anestesia Geral , Pressão Sanguínea/efeitos dos fármacos , Frequência Cardíaca/efeitos dos fármacos , Humanos , Isoquinolinas/farmacologia , Falência Renal Crônica/fisiopatologia , Falência Renal Crônica/cirurgia , Hepatopatias/fisiopatologia , Hepatopatias/cirurgia , Taxa de Depuração Metabólica/efeitos dos fármacos , Pessoa de Meia-Idade , Junção Neuromuscular/efeitos dos fármacos , Fármacos Neuromusculares não Despolarizantes/farmacologiaRESUMO
Increased intra-abdominal pressure (IAP) occurs in pediatric patients with end-stage liver disease and ascites, as well as in children following surgery for diaphragmatic hernia, omphalocele, gastroschisis and orthotopic liver transplantation. Although the hemodynamic response to increased IAP is well described, little information is available regarding the effects of IAP on drug distribution and elimination. We studied the effects of increased IAP (20 mm Hg) on the pharmacokinetics of alfentanil in piglets and compared these findings with those in control animals. Increased IAP appears to have no significant effect on the volume of distribution (0.46 +/- 0.06 vs. 0.61 +/- 0.23 liter/kg), mean residence time (68.8 +/- 27.8 vs. 62.3 +/- 27.8 min) and elimination half-life (47.7 +/- 19.0 vs. 43.2 +/- 19.3 min).
Assuntos
Abdome , Alfentanil/farmacocinética , Alfentanil/farmacologia , Animais , Pressão Sanguínea/efeitos dos fármacos , Débito Cardíaco/efeitos dos fármacos , Meia-Vida , Injeções Intravenosas , Pressão , SuínosRESUMO
The thermogenic effect of nicotine intake after calorie consumption was investigated to determine if nicotine influences metabolic response to a calorie challenge. Smokers and nonsmokers (10 males in each group), matched for body weight, age, and physical fitness, each participated in four sessions that involved consuming a liquid calorie load (4.77 kcal/kg body wt) or water, followed by nicotine (15 micrograms/kg body wt) or placebo via nasal spray every 20 min for 2 h. Energy expenditure was significantly increased above baseline resting metabolic rate (RMR) over the 2 h by nicotine alone (6.5% of RMR, p less than 0.01). However, the combined effect of nicotine after calorie load (20.1% of RMR, p less than 0.001) was not significantly greater than the effect of calorie load alone (18.4% of RMR, p less than 0.001). Smokers and nonsmokers did not differ in baseline RMR or in response to nicotine or calorie load. These results confirm the thermogenic effect of nicotine but suggest that the effect of nicotine after calorie consumption is less than additive.
Assuntos
Ingestão de Energia/fisiologia , Nicotina/farmacologia , Fumar/metabolismo , Administração Intranasal , Adulto , Aerossóis , Metabolismo Basal , Regulação da Temperatura Corporal , Relação Dose-Resposta a Droga , Metabolismo Energético , Frequência Cardíaca , Humanos , Masculino , Nicotina/administração & dosagemRESUMO
Alfentanil's small volume of distribution and short elimination half-life, coupled with its preservation of hemodynamic stability, make it a potentially useful drug for analgesia and anesthesia in neonates. The pharmacokinetics of alfentanil were studied in 5 infants born at 26-35 weeks' gestation and in 5 infants of greater than 36 weeks. All infants were studied in the first 3 days of life. After injection of 25 micrograms/kg alfentanil, there was no significant change in blood pressure or heart rate. No significant difference was observed in volume of distribution (0.84 +/- 0.48 l/kg vs. 0.82 +/- 0.30 l/kg), clearance (1.35 +/- 0.69 ml.kg-1.min-1 vs. 1.7 +/- 0.47 ml.kg-1.min-1), or effective half-life (455 +/- 111 min vs. 328 +/- 48 min) between the two groups. The pharmacokinetic values reported here for both preterm and full-term infants are significantly different from data reported for older children.
Assuntos
Alfentanil/farmacocinética , Alfentanil/sangue , Pressão Sanguínea/efeitos dos fármacos , Idade Gestacional , Meia-Vida , Frequência Cardíaca/efeitos dos fármacos , Humanos , Recém-Nascido , Recém-Nascido Prematuro/metabolismo , Injeções IntravenosasRESUMO
The acute effects of nicotine on resting metabolic rate (RMR) were examined to identify a mechanism that may help explain the inverse association between smoking and body weight. Multiple administrations of two nicotine doses (moderate [15 micrograms/kg body wt] and low [7.5 micrograms/kg body wt]) and a placebo (0 micrograms) were presented to 18 male smokers via nasal-spray solution on three separate occasions while RMR was assessed by computerized open-circuit indirect calorimetry. Plasma nicotine levels confirmed the reliability of dosing. RMR increases of 6% above base line after both moderate and low doses were significantly greater than the 3% increase after the placebo. Subsequent examination of the effects of smoking a nonnicotine cigarette suggested that the small placebo effect was due to acute metabolic consequences of inhalation. These results confirm that intake of nicotine, isolated from tobacco smoke, significantly increases RMR in humans. However, the results also indicate that non-pharmacological, behavioral aspects of smoking may also contribute to acutely increasing RMR in smokers.
Assuntos
Metabolismo/efeitos dos fármacos , Nicotiana , Nicotina/farmacologia , Plantas Tóxicas , Fumar/metabolismo , Adolescente , Adulto , Peso Corporal , Frequência Cardíaca/efeitos dos fármacos , Humanos , Masculino , Nicotina/sangue , PlacebosRESUMO
Because developmental pharmacokinetics appear to be closely associated with anatomic and physiologic changes that occur with growth, we were interested in determining the disposition and elimination of alfentanil in premature infants and older children. The pharmacokinetic profile of alfentanil was determined in 6 premature infants requiring sedation for medical management or analgesia for stressful intensive-care procedures. These pharmacokinetic profiles were compared with pharmacokinetic profiles determined in 9 older infants and children undergoing operative procedures that required invasive monitoring. In both groups the plasma decay curves best fit a 2-compartment model. Compared with older children, premature infants demonstrated a significantly larger apparent volume of distribution (1.0 +/- 0.39 vs. 0.48 +/- 0.19 l/kg), a smaller clearance (2.2 +/- 2.4 vs. 5.6 +/- 2.4 ml/kg/min) and a markedly prolonged elimination half-life (525 +/- 305 vs. 60 +/- 11 min).