Disposition of lorazepam in human beings: Enterohepatic recirculation and first‐pass effect

  title={Disposition of lorazepam in human beings: Enterohepatic recirculation and first‐pass effect},
  author={Robert J. Herman and J Duc Van Pham and Cameron Szakacs},
  journal={Clinical Pharmacology \& Therapeutics},
The effects of neomycin and cholestyramine on the disposition of lorazepam was examined in seven healthy drug‐free men. Half‐life as determined for the oral route was, in all subjects, 15% to 35% less than that determined for the intravenous route. Free oral clearance was slightly but not significantly less than free systemic clearance, but the ratio of the AUC of lorazepam glucuronide corrected for dose was twofold greater by the oral route. Urinary recoveries also differed (71.6% and 50.4… 

Lorazepam‐Valproate Interaction: Studies in Normal Subjects and Isolated Perfused Rat Liver

Summary: Valproate (VPA) has been shown to interact with all the major antiepileptic drugs (AEDs) through two mechanisms of action: displacement from albumin binding sites and inhibition of drug

Effect of neurotrauma on hepatic drug clearance

It is suggested that hepatic oxidative and conjugative metaboHsm increase significantly over time in patients after acute head injury and an awareness of the potential for pharmacokinetic alterations in similarly metabolized drugs used for patients with severe head injuries is recommended.

Role of enterohepatic recirculation in drug disposition: cooperation and complications

Critically appraise the mechanisms of bile formation, factors affecting biliary drug elimination, methods to estimate biliary excretion of drugs, EHC, multiple peak phenomenon and its modeling.

Disposition of Lorazepam in Gilbert's Syndrome: Effects of Fasting, Feeding, and Enterohepatic Circulation

Lorazepam clearances were 20–40% lower in patients with Gilbert's syndrome compared with normals when studied fasting and with neo/chol, or fed and in the control state (P < 0.05 for both).

Disposition of lorazepam in diabetes: differences between patients treated with beef/pork and human insulins

The pharmacokinetics of lorazepam was not altered in patients with insulin-dependent diabetes mellitus, however, it is possible that there are differences in the rate and extent of hepatic glucuronidation and enterohepatic circulation in diabetic patients and between diabetics treated with beef/pork insulin and non-diabetic controls.

The effect of colestipol and cholestyramine on ibuprofen bioavailability in man

A lack of interaction between ibuprofen and colestipol and a potential significant interaction (decrease in rate and extent of absorption of ibUprofen) between cholestyramine and ib uprofen in patients receiving concurrent therapy are indicated.

Hepatic drug clearance in patients with mild cystic fibrosis



First pass conjugation and enterohepatic recycling of oxazepam in dogs; intravenous tolerance of oxazepam in propylene glycol.

In a dog with a chronic biliary fistula 15 mg of oxazepam was given intravenously on two occasions and findings indicate enteral hydrolysis of the conjugates, and a marked enterohepatic recycling or oxzepam.

Clinical pharmacokinetics of lorazepam. I. Absorption and disposition of oral 14C-lorazepam.

Biotransformation to a pharmacologically inactive glucuronide metabolite appeared to be the major mechanism of lorazepam clearance and its metabolites in body fluids were determined by appropriate analytic techniques.

Hepatic and extrahepatic glucuronidation of lorazepam in the dog

It is concluded that the liver is the major site for lorazepam metabolism in dogs; however, appreciable extrahepatic metabolism occurs, partly in non hepatic components of the splanchnic organs which act as a reservoir during drug distribution.

Clinical Pharmacokinetics of Oxazepam and Lorazepam

3-hydroxy benzodiazepine derivatives used as sedatives and anxiolytics and Oral and intramuscular lorazepam are rapidly absorbed, with systemic availability averaging 90 % or more.

Pharmacokinetics and bioavailability of ranitidine in humans.

  • R. Miller
  • Biology
    Journal of pharmaceutical sciences
  • 1984
It is proposed that ranitidine accumulates mainly from the systemic circulation into a depot from which drug and bioreversible drug are spontaneously released in response to food intake.

Effects of aging and liver disease on disposition of lorazepam

It is concluded that the degree of impairment, if any, in the metabolism of lorazepam in patients with liver disease is considerably less than that of certain other drugs including related benzodiazepines.

Clinical pharmacokinetics of lorazepam: a review.

The clinical pharmacokinetics of lorazepam indicate that it is rapidly and readily absorbed, reaching peak concentrations in the blood proportional to the dose approximately 2 hours after oral administration, and the active drug and the glucuronide conjugate are completely eliminated from the blood within 1 week following the last dose.

Lorazepam kinetics in the elderly

The aging process is associated with small changes in the kinetics of lorazepam, as in the case of young individuals, which leads to rapid and nearly complete absorption into the systemic circulation.

The enterohepatic circulation of oxazepam‐O‐glucuronide in guinea‐pigs

Oxazepam-0-glucuronide was purified from rabbit urine by two chloroform extractions and two passages through activated charcoal columns, followed by thinlayer chromatography on silica gel preparative plates as described in detail elsewhere.

Clinical pharmacokinetics of lorazepam. III. Intravenous injection. Preliminary results.

Four healthy male volunteers received 5 mg lorazepam as a single intravenous injection. Concentrations of lorazepam and its glucuronide metabolite were determined in multiple venous blood samples