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Hepatic and extrahepatic glucuronidation of lorazepam in the dog

, : Hepatic and extrahepatic glucuronidation of lorazepam in the dog. Hepatology 1(4): 329-335

The pharmacokinetic disposition of lorazepam was investigated in sham-operated aneshetized dogs, dogs with hepatic devascularization, and dogs with total splanchnic devascularization following i.v. administration of 0.3 mg per kg of the drug. In sham-operated dogs, lorazepam distribution was extensive (100 +/- 15.2 liters) and clearance approximately expected liver blood flow (971 +/- 91 ml per min). Lorazepam glucuronide levels in plasma rose rapidly in the first hour and reached a plateau by 5 hr. Urinary recovery of the conjugate in 5 hr was 45% of administered dose. Hepatic devascularization resulted in 39% reduction in distribution volume, and 89% reduction in clearance; however, there was still 105 +/- 88 ml per min of extrahepatic lorazepam clearance. Five-hour urinary recovery of conjugate decreased by 80%. Total splanchnic devascularization resulted in 37% further reduction in extrahepatic clearance, almost complete inhibition of urinary recovery of conjugate, and further reduction in the volume of distribution. It is concluded that the liver is the major site for lorazepam metabolism in dogs; however, appreciable extrahepatic metabolism occurs, partly in nonhepatic components of the splanchnic organs which act as a reservoir during drug distribution.


PMID: 6116660

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Stein, G.; Franke, S.; Mahiout, A.; Schneider, S.; Sperschneider, H.; Borst, S.; Vienken, J., 2001: Influence of dialysis modalities on serum AGE levels in end-stage renal disease patients. Background. The accumulation of advanced glycation end-products (AGEs) in end-stage renal disease (ESRD) influenced by dialysis modalities is of current interest. Highly permeable membranes in haemodialysis or haemofiltration should be able to eli...

Schindler, W.G., 1986: The stereo microscope: an aid to evaluate root canal debridement and obturation. Journal of Endodontics 12(8): 359-362

Fawcett, J.; Smith, G.D.; Peters, T.J., 1988: Effect of fasting on the hepatic processing of insulin. Frequency-density distributions of [125I]insulin were studied from control (fed) and starved (18 h) rats. The total amount of insulin taken up by the liver was not significantly different between fed and starved rats. The amount of insulin over di...

Syed, D.N.; Lall, R.K.; Chamcheu, J.Christopher.; Haidar, O.; Mukhtar, H., 2015: Involvement of ER stress and activation of apoptotic pathways in fisetin induced cytotoxicity in human melanoma. The prognosis of malignant melanoma remains poor in spite of recent advances in therapeutic strategies for the deadly disease. Fisetin, a dietary flavonoid is currently being investigated for its growth inhibitory properties in various cancer mode...

Stahr, N.; Holzapfel, G.; Hardeland, R., 1980: Phase shifting of the Gonyaulax clock by puromycin. Continuous treatment with high doses of puromycin suppresses the circadian rhythm of bioluminescence in G. polyedra. When given in submaximal doses, which are inhibitory only in the 3rd or 4th cycle, the antibiotic causes phase delays. At a higher...

Caminiti, F., 1957: Cholinesterase activity in blood & uterine muscle in fibromatosis. Archivio di Ostetricia E Ginecologia 62(2): 97-110

Prescher, F.; Lindgren, D.; Almqvist, C.; Kroon, J.; Lestander, T., A.; Mullin, T., J., 2007: Female fertility variation in mature Pinus sylvestris clonal seed orchards. Female fertility is the basis for the output of seeds from clonal orchards and its variation is of major interest for the economics and biology of seed orchards, especially for the efficiency and diversity of seed orchard crops. Assessments of fe...

Villeneuve, F., 1986: Burr-knots, their development and methods of control. Burrknot (aerial root primordia) formation and incidence are discussed. Numbers of burrknots on several apple rootstocks (grafted with cv. Golden Delicious 972A) are tabulated. At Marsillargues MM.111, M.26 and MM.106 are particularly susceptible...

Salari, P.; Abdollahi, M., 2012: Behind the pathogenesis of osteoporosis and cardiovascular diseases. Archives of Medical Science 7(4): 568-569

Miller D.C., 1984: Meningeal gliomatosis with negative cerebrospinal fluid cytology the value of glial fibrillary acidic protein staining. Neurology: 1611-1615