The fate and movements of aquarium-released giant trevally Caranx ignobilis inferred from acoustic telemetry.

Movements of four adult giant trevally Caranx ignobilis were tracked using passive acoustic telemetry after being released from uShaka Sea World Aquarium in Durban, South Africa, where they had been kept on display for a period of 8 years. All four individuals were detected on a large network of deployed acoustic receivers for a minimum of 3 months to a maximum of over 6 years. Their movements were compared to 43 wild-caught and tagged C. ignobilis over a similar period and two individuals adopted movement behavior similar to that of their conspecifics, including repeated annual seasonal migrations to a known spawning aggregation site. This study shows that with good animal husbandry, indigenous fish kept in captivity can be released back into the wild and not only survive but adopt natural movement behavior and contribute to future generations of their species.

Disposition and metabolism of the cathepsin K inhibitor odanacatib in humans.

Odanacatib is a selective inhibitor of the cathepsin K enzyme that is expressed in osteoclasts involved in the degradation of bone organic matrix, and is being developed as a novel treatment of osteoporosis. Odanacatib has demonstrated increases in bone mineral density in postmenopausal women and is undergoing a pivotal phase III trial. The absorption, metabolism, and excretion of [(14)C]odanacatib were studied in healthy male volunteers (n = 6) after a single oral dose of 25 mg (100 µCi). Plasma, urine, and fecal samples were collected at intervals up to 34 days postdose. The pharmacokinetics of odanacatib were characterized by slow absorption (mean time to achieve maximum plasma concentration of 14.2 hours) and long apparent elimination half-life (mean t1/2 96.7 hours); 74.5% of the dose was recovered in feces and 16.9% in urine, resulting in a total recovery of 91.4%. Seven metabolites were identified in urine; the major pathway (methyl hydroxylation producing M8 and its derivatives) was largely dependent on CYP3A. Metabolites and odanacatib accounted for 77% and 23% of urinary radioactivity, respectively. In fecal extracts, the only radioactive components identified were odanacatib (60.9%) and M8 (9.5%). The fraction of odanacatib in feces derived from absorbed drug was estimated using a bioavailability value obtained from the results of a separate intravenous study. Collectively, the data indicate that odanacatib has a long t1/2 on account of its low metabolic intrinsic clearance, and that metabolism (principally mediated by CYP3A) and excretion of intact parent compound account for ∼70% and ∼30% of the clearance of odanacatib in humans.

A pharmacokinetic and pharmacodynamic drug interaction study of acamprosate and naltrexone.

Acamprosate and naltrexone have each demonstrated safety and efficacy for alcohol dependence in placebo-controlled clinical trials. There is scientific and clinical interest in evaluating these drugs in combination, given their high tolerability, moderate effect sizes, different pharmacological profiles and potentially different effects on drinking outcomes. Thus, this is the first human pharmacokinetic and pharmacodynamic drug interaction study of acamprosate and naltrexone. Twenty-four normal, healthy adult volunteers participated in a double-blind, multiple dose, within subjects, randomized, 3-way crossover drug interaction study of the standard therapeutic dose of acamprosate (2 g/d) and the standard therapeutic dose of naltrexone (50 mg/d), given alone and in combination, with seven days per treatment condition and seven days washout between treatments. Blood samples were collected on a standardized schedule for pharmacokinetic analysis of naltrexone, 6-beta-naltrexol, and acamprosate. A computerized assessment system evaluated potential drug effects on cognitive functioning. Coadministration of acamprosate with naltrexone significantly increased the rate and extent of absorption of acamprosate, as indicated by an average 33% increase in acamprosate maximum plasma concentration, 33% reduction in time to maximum plasma concentration, and 25% increase in area under the plasma concentration-time curve. Acamprosate did not affect the pharmacokinetic parameters of naltrexone or 6-beta-naltrexol. A complete absence of negative interactions on measures of safety and cognitive function supports the absence of a contraindication to co-administration of acamprosate and naltrexone in clinical practice.