No abstract

No abstract

Ciliochoroidal detachments occur under a variety of pathological circumstances and are most commonly noted following intraocular surgery where hypotony is combined with postoperative inflammation. Although the condition is easily recognized, the pathophysiologic mechanisms involved are not well understood. In this review, the pathophysiologic mechanisms are summarized, with special emphasis on fluid dynamics within the suprachoroidal space. The clinical features, etiology and treatment of ciliochoroidal detachments are also reviewed.

Aim The aim of this study was to characterize the pharmacokinetics and pharmacodynamics of donepezil HCl, a new, chemically distinct and specific acetylcholinesterase (AChE) inhibitor for the treatment of Alzheimer’s disease, following multiple‐dose administration. Methods This was a double‐blind, randomized, placebo‐controlled, multiple‐dose study in healthy male volunteers (n=27). Three dose levels were investigated in sequential order: 1, 3 and 5 mg. Each dose was administered orally, once a day, for 21 consecutive days. Donepezil concentrations in plasma were quantified by HPLC. Pharmacodynamic activity was determined by the radioenzymatic measurement of erythrocyte membrane acetylcholinesterase (rbc‐AChE) inhibition. Results The pharmacokinetic disposition of donepezil was observed to be dose proportional. The mean terminal disposition half‐life was 79.5±19.0 h which resulted in a slow approach to steady state (14–21 days). A four‐ to sixfold increase in donepezil plasma concentration was observed during this time; however, no further increase was evident after achievement of steady state. The mean donepezil plasma concentration at steady state (Css ) was 14.2 ng ml−1. Neither the rate of accumulation nor the rate of clearance was dose dependent. Inhibition of rbc‐AChE was directly correlated with donepezil concentration over a wide concentration range, with the higher concentrations showing the expected hyperbolic relationship. Donepezil was well tolerated by all subjects with no clinically significant changes in laboratory or physical parameters observed at any dose. Conclusions The pharmacokinetics of donepezil were found to be dose proportional following the administration of multiple doses to healthy volunteers. A predictable relationship was also observed between plasma donepezil concentrations and rbc‐AChE inhibition. The half‐life of donepezil makes it suitable for once‐daily dosing.

No abstract