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The liver is a complex organ that performs vital functions of synthesis, heat production, detoxification and regulation; its failure carries a highly critical risk. At the end of the last century, some artificial liver devices began to develop with the aim of being used as supportive therapy until liver transplantation (bridge-to-transplant) or liver regeneration (bridge-to-recovery). The well-recognized devices are the Molecular Adsorbent Recirculating System™ (MARS™), the Single-Pass Albumin Dialysis system and the Fractionated Plasma Separation and Adsorption system (Prometheus™). In the following years, experimental works and early clinical applications were reported, and to date, many thousands of patients have already been treated with these devices. The ability of artificial liver support systems to replace the liver detoxification function, at least partially, has been proven, and the correction of various biochemical parameters has been demonstrated. However, the complex tasks of regulation and synthesis must be addressed through the use of bioartificial systems, which still face several developmental problems and very high production costs. Moreover, clinical data on improved survival are conflicting. This paper reviews the progress achieved and new data published on artificial liver support systems over the past decade and the prospects for these devices.

The elderly are likely candidates to receive analgesics for pain from a variety of etiologies. Ketorolac tromethamine is a nonsteroidal, analgesic, anti-inflammatory, antipyretic investigational drug with anti-prostaglandin synthetase activity. Sixteen healthy, young men (mean age 30 years and mean weight 75 kg) and 13 healthy, elderly subjects (11 men and two women; mean age 72 years and mean weight 75 kg) participated in an open-label, parallel single-dose study. On each day of ketorolac tromethamine administration the subjects fasted overnight and for 2 hours post-dose. A single intramuscular (IM) dose of 30 mg of ketorolac tromethamine was administered followed by an oral dose (PO) of 10 mg after a 1 week washout period for the elderly subjects. Plasma samples were taken from 0 through 48 hours post-dose and analyzed for ketorolac by HPLC. The elimination of ketorolac was decreased slightly in the elderly following both doses, as evidenced by a prolongation in half-life (4.7 to 6.1 hours for PO and 4.5 to 7.0 hours for IM) and a reduced total plasma clearance compared to the young adult subjects. These differences were statistically significant (P less than .001). Considerable overlap frequently was observed when comparing the range of values obtained for the young and elderly for plasma half-life, clearance, AUC, Tmax and Cmax. The absorption of ketorolac tromethamine was not altered substantially in the elderly following either dose route. Ketorolac plasma protein binding was not altered substantially in the elderly. The present results show that the elderly may need slightly less frequent dosing of ketorolac than young adults to maintain similar plasma levels.(ABSTRACT TRUNCATED AT 250 WORDS)

This double-blind, placebo-controlled, four-period cross-over study was undertaken to evaluate the sustained-release characteristics of long-acting propranolol hydrochloride (Inderal LA, Ayerst Laboratories, New York, NY) 60 mg qd, to compare the pharmacokinetic and pharmacodynamic properties of this formulation with conventional propranolol 20 mg tid, and to evaluate the proportionality of long-acting propranolol 60 mg (LA 60 mg) and long-acting propranolol 80 mg (LA 80 mg). Pharmacodynamic effects were evaluated in 34 healthy subjects by assessing heart rate, systolic blood pressure, and the product of heart rate and systolic blood pressure (double product) after exercise-induced tachycardia following both acute (day 1) and steady state (day 4) drug administration. The Cmax following administration of LA 60 mg was 9.5 and 11.4 ng/mL on days 1 and 4, respectively, compared with 18.8 and 20.0 ng/mL with 20 mg tid (P less than .0001). The tmax for LA 60 mg was significantly later (P less than .0001) than for conventional propranolol. Additionally, the apparent plasma half-life was significantly longer (P less than .0001) than with conventional propranolol. The LA 60-mg formulation was dose proportional to the LA 80-mg formulation. Pharmacodynamic evaluations showed no significant differences between LA 60 mg and 20 mg tid at any times tested with either acute or steady state dosing. This study demonstrates that LA 60 mg displays characteristics of a sustained-release formulation, is proportional with LA 80 mg, and produces pharmacodynamic effects that are similar to 20-mg tid dosing.