Milne R W, Sloan P A, McLean C F, Mather L E, Nation R L, Runciman W B, Rutten A J, Somogyi A A
School of Pharmacy, University of South Australia, Adelaide.
Drug Metab Dispos. 1993 Nov-Dec;21(6):1151-6.
A sheep preparation was used to examine the regional formation and extraction of morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G), relative to the regional extraction of morphine, at four morphine dose rates. On separate occasions, four ewes received a 15-min loading infusion of morphine sulfate, followed by a constant infusion at 2.5, 5, 10, or 20 mg/hr for an additional 5.75 hr. During the 5th to 6th hr of infusion, blood samples were collected simultaneously from the aorta, pulmonary artery, hepatic vein, hepatic portal and renal veins, posterior vena cava, and coronary and sagittal sinuses. Urine was collected for 48 hr. Morphine, M3G, and M6G in plasma and urine were determined simultaneously by HPLC. The blood/plasma concentration ratio (lambda) for morphine, M3G, and M6G was determined in spiked "blank" blood. Steady-state plasma concentrations were achieved during the sampling period, and dose-normalized concentrations were independent of the infusion rate. There was significant (p < 0.05) extraction (mean +/- SD) of morphine by the liver (0.676 +/- 0.014) and kidney (0.602 +/- 0.039), net extraction of M3G (0.106 +/- 0.046) and M6G (0.104 +/- 0.030) by the kidney, and net formation of M3G (-0.057 +/- 0.017) by the gut. The mean lambda for morphine, M3G, and M6G was 1.25 +/- 0.17, 0.80 +/- 0.03, and 0.82 +/- 0.09, respectively. The mean total body clearance of morphine with respect to blood was 1.58 +/- 0.27 liters/min. Mean (+/-SD) percentage urinary recoveries as morphine, M3G, and M6G were 14.7 +/- 8.5, 75.4 +/- 11.1, and 0.49 +/- 0.39, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
采用绵羊实验，以研究在四种吗啡剂量率下，相对于吗啡的局部摄取，吗啡-3-葡萄糖醛酸苷（M3G）和吗啡-6-葡萄糖醛酸苷（M6G）的局部生成和提取情况。在不同时间，四只母羊先接受15分钟的硫酸吗啡负荷输注，随后分别以2.5、5、10或20毫克/小时的速率持续输注5.75小时。在输注的第5至6小时期间，同时从主动脉、肺动脉、肝静脉、肝门静脉和肾静脉、后腔静脉以及冠状窦和矢状窦采集血样。收集48小时尿液。采用高效液相色谱法同时测定血浆和尿液中的吗啡、M3G和M6G。在加标的“空白”血液中测定吗啡、M3G和M6G的血/血浆浓度比（λ）。在采样期间达到稳态血浆浓度，且剂量标准化浓度与输注速率无关。肝脏（0.676±0.014）和肾脏（0.602±0.039）对吗啡有显著（p<0.05）摄取，肾脏对M3G（0.106±0.046）和M6G（0.104±0.030）有净提取，肠道对M3G有净生成（-0.057±0.017）。吗啡、M3G和M6G的平均λ分别为1.25±0.17、0.80±0.03和0.82±0.09。吗啡相对于血液的平均全身清除率为1.58±0.27升/分钟。吗啡、M3G和M6G的平均（±标准差）尿回收率分别为14.7±8.5、75.4±11.1和0.49±0.39。（摘要截短于250字）
