Gabapentin: pharmacokinetics, efficacy, and safety

Gabapentin is a new antiepileptic drug (AED) with an attractive pharmacokinetic profile. It is absorbed by an active and saturable transport system, and has a high volume of distribution. Gabapentin is not bound to plasma proteins, does not induce hepatic enzymes and is not metabolized. At steady state, it has a half-life of 6-8 h, and is eliminated unchanged by renal route with a plasma clearance proportional to the creatinine clearance. It is devoid of significant drug-drug interactions when administered with the established AEDs or with oral contraceptives. Gabapentin used as an add-on AED significantly reduced the frequency of partial seizures and secondarily generalized tonic-clonic seizures in three large double-blind, placebo-controlled, parallel-group clinical trails. It is well tolerated, with transient somnolence and dizziness being the most frequent adverse effects. Although the mechanism of action of gabapentin is not fully established, there is strong evidence to suggest a novel mechanism of action. Gabapentin is a unique and promising drug that could improve the quality of life of patients with epilepsy and is a welcome addition to the armamentarium of currently available AEDs for the treatment of patients with seizures of partial onset.     

Superoxide: a two-edged sword

Superoxide (O2-) is the compound obtained when oxygen is reduced by one electron. For a molecule with an unpaired electron, O2- is surprisingly inert, its chief reaction being a dismutation in which it reacts with itself to form H2O2 and oxygen. The involvement of O2- in biological systems was first revealed by the discovery in 1969 of superoxide dismutase, an enzyme that catalyzes the dismutation of O2-. Since then it has been found that biological systems produce a bewildering variety of reactive oxidants, all but a few arising ultimately from O2-. These oxidants include O2- itself, H2O2 and alkyl peroxides, hydroxyl radical and other reactive oxidizing radicals, oxidized halogens and halamines, singlet oxygen, and peroxynitrite. These various oxidants are able to damage molecules in their environment, and are therefore very dangerous. They are thought to participate in the pathogenesis of a number of common diseases, including among others malignancy, by their ability to mutate the genome, and atherosclerosis, by their capacity for oxidizing lipoproteins. Their properties are put to good use, however, in host defense, where they serve as microbicidal and parasiticidal agents, and in biological signalling, where their liberation in small quantities results in redox-mediated changes in the functions of enzymes and other proteins.     

Risk factors for chronic graft-versus-host disease after bone marrow transplantation: a retrospective single centre analysis

We retrospectively compared the changes in serum albumin concentration and colloid osmotic pressure between survivors and nonsurvivors of prolonged (> or = 7 days) critical illness over a 2-year period from 1 July 1995. All patients had serum albumin measured daily, and colloid osmotic pressure measured 5 days a week, throughout their ICU admission. They received crystalloid and colloid infusions as well as parenteral or enteral feeding. Infusions of albumin were not used to treat hypoalbuminaemia. One hundred and forty-five patients were included, 66 nonsurvivors and 79 survivors. Nonsurvivors were significantly older than survivors [mean (95% CI): 58 (3.8) and 49 (4.1) years, respectively] and had a greater risk of death [mean (95% CI): 0.44 (0.06) and 0.28 (0.05); p < 0.05]. There was no significant difference in gender, APACHE II score [mean (95% CI): 22 (2.7) (nonsurvivors); 18 (2.3) (survivors)] or length of stay [median (interquartile range): 14 (9-27) days (nonsurvivors); 15 (9-26) days (survivors)]. There was no difference between the two groups in the absolute minimum serum albumin concentrations reached, the time to reach that minimum or the minimum in the first 7 days. However, nonsurvivors had a significantly lower mean serum albumin concentration: [mean (95% CI): 15.7 (5.1) g.l-1 compared with 18.3 (4.6) g.l-1 in survivors; p < 0.05]. They also had a lower recovery mean (the weighted mean after the minimum value): [mean (95% CI): 13.3 (5.1) g.l-1 (nonsurvivors) and 18.6 (5.3) g.l-1 (survivors); p < 0.01]. Analysis of colloid osmotic pressure results showed no difference between the groups in mean, minimum or recovery mean. Regression analysis of mean colloid osmotic pressure and albumin revealed that albumin only contributed 17% of the colloid osmotic pressure in these patients. The similar decrease in albumin in nonsurvivors and survivors may reflect the acute inflammatory response and/or haemodilution. However, survivors showed an ability to increase serum albumin concentrations, possibly owing to resumption of synthesis. The colloid osmotic pressure varied little between or within either group of patients, possibly because of the use of artificial colloids. There was no relationship between death and colloid osmotic pressure.