Duarte A G, Dhand R, Reid R, Fink J B, Fahey P J, Tobin M J, Jenne J W
Division of Pulmonary and Critical Care Medicine, Edward Hines Jr. Veterans Affairs Hospital, Loyola University of Chicago Stritch School of Medicine, Hines, IL 60141, USA.
Am J Respir Crit Care Med. 1996 Dec;154(6 Pt 1):1658-63. doi: 10.1164/ajrccm.154.6.8970351.
In mechanically ventilated patients, systemic blood levels of inhaled drugs reflect absorption from the lower respiratory tract alone since, unlike nonintubated patients, oropharyngeal and gastrointestinal absorption cannot occur. To determine the efficiency of aerosol administration by a metered-dose inhaler (MDI), we measured serum albuterol levels after administration by a MDI and spacer to nine mechanically ventilated patients (10 puffs) and to 10 healthy subjects (six puffs). Serum albuterol levels (+/- SEM) quantitated by high-performance liquid chromatography and electrochemical detection were: 0.09 +/- 0.04 mg/ml/puff at baseline, 0.66 +/- 0.10 at 5 min, 0.98 +/- 0.10 at 10 min, 0.56 +/- 0.08 at 15 min, and 0.37 +/- 0.03 at 30 min in mechanically ventilated patients versus zero at baseline, 0.89 +/- 0.12 at 5 min, 1.27 +/- 0.13 at 10 min, 0.84 +/- 0.09 at 15 min, and 0.53 +/- 0.07 at 30 min in control subjects (p > or = 0.07 at 5, 10, and 30 min; p < or = 0.05 at baseline and at 15 min). Area under the curve (AUC0-30) in the mechanically ventilated patients was 16.8 +/- 1.4 versus 23.4 +/- 1.9 ng/ml/puff x min in control subjects (p = 0.014). In summary, administration of albuterol with a MDI achieved a profile of serum levels in mechanically ventilated patients similar to that in healthy control subjects, but the peak serum level and systemic bioavailability (AUC0-30) were lower in the patients. In conclusion, serum levels reliably assess lower respiratory tract deposition of albuterol, and show that MDIs are more efficient for aerosol delivery in mechanically ventilated patients than was previously reported in studies using radiolabeled aerosols.
在机械通气患者中，吸入药物的全身血药水平仅反映来自下呼吸道的吸收情况，因为与未插管患者不同，口咽和胃肠道吸收不会发生。为了确定定量吸入器（MDI）气溶胶给药的效率，我们测量了通过MDI和储雾罐对9名机械通气患者（10喷）和10名健康受试者（6喷）给药后的血清沙丁胺醇水平。通过高效液相色谱和电化学检测定量的血清沙丁胺醇水平（±SEM）为：机械通气患者基线时为0.09±0.04mg/ml/喷，5分钟时为0.66±0.10，10分钟时为0.98±0.10，15分钟时为0.56±0.08，30分钟时为0.37±0.03；而对照组受试者基线时为零，5分钟时为0.89±0.12，10分钟时为1.27±0.13，15分钟时为0.84±0.09，30分钟时为0.53±0.07（5、10和30分钟时p≥0.07；基线和15分钟时p≤0.05）。机械通气患者的曲线下面积（AUC0 - 30）为16.8±1.4，而对照组受试者为23.4±1.9ng/ml/喷×分钟（p = 0.014）。总之，使用MDI给予沙丁胺醇后，机械通气患者的血清水平曲线与健康对照受试者相似，但患者的血清峰值水平和全身生物利用度（AUC0 - 30）较低。总之，血清水平可靠地评估了沙丁胺醇在下呼吸道的沉积情况，并表明MDI在机械通气患者中气溶胶递送方面比以前使用放射性标记气溶胶的研究所报道的更有效。
