猪在新生儿发育过程中，血浆和脑脊液中吗啡的分布情况会有所不同。

Disposition of morphine in plasma and cerebrospinal fluid varies during neonatal development in pigs.

作者信息

Rai Aarati, Bhalla Shaifali, Rebello Sam S, Kastrissios Helen, Gulati Anil

机构信息

Department of Biopharmaceutical Sciences, College of Pharmacy, The University of Illinois at Chicago, Chicago, IL 60612, USA.

出版信息

J Pharm Pharmacol. 2005 Aug;57(8):981-6. doi: 10.1211/0022357056505.

DOI:10.1211/0022357056505

PMID:16102253

Abstract

The pharmacological effects of morphine are mediated via the central nervous system (CNS) but its clearance from the CNS in neonates has not been investigated. We have proposed that neonatal development of the blood-brain barrier affected CNS clearance mechanisms and CNS exposure to morphine. Male piglets (n = 5) aged one, three and six weeks were given morphine sulfate (0.5 mg kg(-1), i.v.). Serial blood and cerebrospinal fluid (CSF) samples were withdrawn over 360 min after morphine administration. Morphine concentration was measured by radioimmunoassay. A three-compartment model was fitted to individual data. Estimated parameters were reported as median and range. The peak morphine concentrations in plasma were not significantly different in the one-, three- or six-week-old piglets. Plasma clearance at one week (4.5, 3.8-8.6 mL min(-1) kg(-1)) was significantly lower than at three weeks (30.0, 19.1- 39.0 mL min(-1) kg(-1)) and six weeks (37.0, 29.7-82.8 mL min(-1) kg(-1)). The peak morphine concentration in CSF at one week (59.84, 31-67 ng mL(-1)) was higher than at three weeks (18.8, 17.7-25 ng mL(-1)) and six weeks (24.51, 16.5-84 ng mL(-1)), while CSF clearance was lower at one week (1.0, 0.18-9 mL min(-1) kg(-1)) compared with three weeks (6.2, 2.3-9.3 mL min(-1) kg(-1)) and six weeks (3.95, 1.3-85.7 mL min(-1) kg(-1)). Apparent plasma:CSF transfer ratio at one week was greater than at three and six weeks. The reduced plasma and CSF morphine clearance in early infancy resulted in elevated systemic and central morphine exposure in neonatal pigs.

摘要

吗啡的药理作用通过中枢神经系统（CNS）介导，但尚未对新生儿中枢神经系统中吗啡的清除情况进行研究。我们提出，血脑屏障的新生儿发育影响中枢神经系统清除机制以及中枢神经系统对吗啡的暴露。给1周龄、3周龄和6周龄的雄性仔猪（n = 5）静脉注射硫酸吗啡（0.5 mg kg⁻¹）。在给予吗啡后360分钟内采集系列血液和脑脊液（CSF）样本。通过放射免疫分析法测量吗啡浓度。对个体数据拟合三室模型。估计参数报告为中位数和范围。1周龄、3周龄或6周龄仔猪血浆中的吗啡峰值浓度无显著差异。1周龄时的血浆清除率（4.5，3.8 - 8.6 mL min⁻¹ kg⁻¹）显著低于3周龄时（30.0，19.1 - 39.0 mL min⁻¹ kg⁻¹）和6周龄时（37.0，29.7 - 82.8 mL min⁻¹ kg⁻¹）。1周龄时脑脊液中的吗啡峰值浓度（59.84，31 - 67 ng mL⁻¹）高于3周龄时（18.8，17.7 - 25 ng mL⁻¹）和6周龄时（24.51，16.5 - 84 ng mL⁻¹），而1周龄时的脑脊液清除率（1.0，0.18 - 9 mL min⁻¹ kg⁻¹）低于3周龄时（6.2，2.3 - 9.3 mL min⁻¹ kg⁻¹）和6周龄时（3.95，1.3 - 85.7 mL min⁻¹ kg⁻¹）。1周龄时的表观血浆：脑脊液转运比大于3周龄和6周龄时。婴儿早期血浆和脑脊液中吗啡清除率降低导致新生仔猪全身和中枢吗啡暴露增加。