Paracetamol absorption from a feeding jejunostomy.

Disposition of paracetamol oral elixir was determined in two male patients after administration via feeding jejunostomy and compared with four male controls who received the same dose by mouth. Area under the plasma concentration-time curve, elimination half-life, and time to maximum concentration were similar in both groups after 650 mg paracetamol elixir. The absolute amounts and ratio of paracetamol glucuronide to sulphate, the major urinary metabolites after therapeutic paracetamol doses, were similar after jejunal administration as compared to oral administration. Paracetamol is absorbed and biotransformed in a similar manner after either jejunal or oral administration. Therefore, it may be administered effectively via jejunostomy tube in patients who require this route of administration.     

Effect of cirrhosis and renal failure on the kinetics of clotiazepam

Summary The kinetics of a single 5-mg oral dose of the thienodiazepine clotiazepam was evaluated in a series of patients with biopsy-proven cirrhosis, and in patients with renal insufficiency requiring maintenance hemodialysis, compared to healthy matched controls. Clotiazepam volume of distribution (V_z) was significantly smaller in cirrhotic patients than in controls (1.83 vs 2.57 l/kg), and total clearance was likewise reduced (2.15 vs 3.15 ml/min/kg). Elimination half-life was similar between groups (10.0 vs. 10.2h). There were no significant differences between renal failure and control patients in clotiazepam V_z, oral clearance, or elimination half-life. Thus cirrhosis is associated with reduced clearance of clotiazepam, probably due to impairment of its microsomal oxidation. However clotiazepam disposition is not significantly altered in dialysis-dependent renal insufficiency patients.Supported in part by Grant OC 10/6–4 from Deutsche Forschungsgemeinschaft, and Grant MH-34223 from the United States Public Health Service.     

Differential effects of chronic lorazepam and alprazolam on benzodiazepine binding and GABAA-receptor function.

1. Chronic benzodiazepine administration has been associated with tolerance and with downregulation of gamma-aminobutyric acidA (GABAA)-receptor binding and function. However, effects of individual benzodiazepines on brain regions have varied. 2. To compare the effects of chronic lorazepam and alprazolam, we have administered these drugs to mice for 1 and 7 days (2 mg kg-1 day-1) and determined benzodiazepine receptor binding in vivo with and without administration of CL 218,872, 25 mg kg-1 i.p., and GABA-dependent chloride uptake in 3 brain regions at these time points. 3. Benzodiazepine binding was decreased in the cortex and hippocampus at day 7 compared to day 1 of lorazepam, with an increase in CL 218,872-resistant (Type 2) sites in both regions. Maximal GABA-dependent chloride uptake was also decreased in the cortex and hippocampus at day 7. 4. Binding was decreased only in the cortex after 7 days of alprazolam, with no significant change in Type 2 binding. Maximal GABA-dependent chloride uptake was also decreased only in the cortex. 5. These data suggest that the effects of chronic benzodiazepine administration on the GABAA-receptor may be both region-specific and receptor subtype-specific.