AimsThe prevalence of hyperuricaemia and gout increases with age as does the incidence of adverse effects to allopurinol, the major uric acid lowering drug. The present study was performed to compare the disposition and effects of allopurinol and its active metabolite oxipurinol in elderly and young subjects without major health problems. Methods Ten elderly (age range 71-93 years) and nine young subjects (24-35 years) received an oral dose of 200 mg allopurinol in an open, single dose, cross sectional design. Four of these individuals were additionally dosed with 200 mg allopurinol intravenously. Plasma and urine concentrations of allopurinol, oxipurinol, hypoxanthine, xanthine, and uric acid were measured by h.p.l.c. Results Total clearance of allopurinol was not different in elderly (15.7±3.8 ml min −1 kg −1 , mean±s.e. mean) and young subjects (15.7±2.1), whereas total clearance of oxipurinol was significantly reduced in the aged (0.24±0.03) compared with young controls (0.37±0.05) as was the distribution volume of oxipurinol (0.60±0.09 and 0.84±0.07 l kg −1 , respectively). Oxipurinol was eliminated primarily by the kidneys, allopurinol by metabolism. Fractional peroral bioavailability of allopurinol was 0.81±0.16 (n=4, two elderly and two young subjects). Although maximal plasma concentrations of oxipurinol were significantly higher in elderly (5.63±0.83 mg ml −1 ) than in young persons (3.75±0.25) as was the area under the oxipurinol plasma concentration-time curve, AUC (260±46 and 166±23 mg ml −1 h, respectively), the pharmacodynamic effect of oxipurinol was smaller in elderly than young subjects (time-dependent decrease of plasma uric acid 83±30 mg ml −1 h in elderly compared with 176±21 in young controls). Oxipurinol increased the renal clearance of xanthine, suggesting inhibition of tubular xanthine reabsorption by oxipurinol. Conclusions Although allopurinol elimination is not reduced in the aged, that of its active metabolite oxipurinol is because of an age-dependent decline in renal function. Xanthine oxidase inhibition by oxipurinol appears to be reduced in old age. In addition to its uricostatic action, oxipurinol has a xanthinuric effect which is also diminished in the elderly.

Amphetamine congeners [e.g., 3,4-methylenedioxymetamphetamine (MDMA), or "ecstasy"] are substrates for monoamine transporters (i.e., the transporters for serotonin, norepinephrine, and dopamine); however, their in vivo-action relies on their ability to promote monoamine efflux. The mechanistic basis for this counter transport remains enigmatic. We tested the hypothesis that outward transport is contingent on the oligomeric nature of neurotransmitter transporters by creating a concatemer of the serotonin transporter and the amphetamineresistant GABA transporter. In cells expressing the concatemer, amphetamine analogs promoted GABA efflux and blunted GABA influx. In contrast, the natural substrates serotonin and GABA only cause mutual inhibition of influx via the other trans

A rapid and low-cost assay for simultaneous vigabatrin (VGA) and gabapentin (GBP) determination is described that can be performed with simple HPLC instrumentation. The method involves derivatization of the primary amine group of VGA and GBP with dansyl chloride followed by isocratic separation (column: microBondapak C-18, 10 microm, 300 x 3.9 mm; mobile phase: 50 mmol/L NaH(2)PO(4) in 40% acetonitrile) at 50 degrees C and fluorometric detection (excitation and emission wavelength: 318 and 510 nm, respectively) of the fluorescent product, which is stable for at least 7 days. Correlation coefficients of the calibration curves are >0.999 with a lower limit of detection of 0.3 microg/mL. Between- and within-run coefficients of variation are below 4.5%, and assay time is 15 minutes. This method may be used for therapeutic drug monitoring in the case of GBP and to control patient compliance in the case of VGA.

In a cross-sectional study the pharmacokinetics of indomethacin were studied in old and young adults without manifest organ failure. Total clearance of indomethacin after a single oral dose of 50mg was 0.8 ml/min/kg in elderly individuals (mean 79.5 +/- 1.3 years) compared with 1.4 ml/min/kg in younger individuals (mean 36.9 +/- 3.0 years). The apparent elimination rate constant averaged 0.23 h-1 in the aged and 0.32 h-1 in the young people. Oral bioavailability was close to 1 in the young but 0.77 in the elderly. The apparent volume of distribution was similar in each group. Based on these results it is suggested that the maintenance dose of indomethacin be reduced by 25% in the elderly.

Cerebral arteriovenous malformations (AVMs) are considered to be congenital disorders. However, their familial occurrence has so far been described in only 19 families in the literature. The authors report on two cases in one family and review the literature. A 45-year-old female subject with sudden onset of headache and vomiting due to a subarachnoid haemorrhage from a small AVM in the posterior part of the corpus callosum near the midline on the left side was studied. Irradiation of the AVM using Leksell's gamma knife led to its complete obliteration. Her older sister presented with temporal seizures at the age of 49 and later also with left hemiparesis, left hemihypaesthesia and dizziness - caused by a large AVM in the right temporal lobe. This AVM was treated by a combination of embolization and irradiation by the Leksell's gamma knife.