Comparison of the pharmacokinetics and pharmacodynamics of the aldose reductase inhibitors, AL03152 (RS), AL03802 (R), and AL03803 (S).

The pharmacokinetics of AL03152 (RS) and its enantiomers, AL03802 (R) and AL03803 (S), were studied in the Sprague-Dawley rat following intravenous bolus administration. The enantiomers had differing pharmacokinetic profiles, while the racemic compound exhibited pharmacokinetic parameters approximating the mean values of the individual enantiomers. The total clearance (CLT) values of the two enantiomers were similar, but the intrinsic clearance (Cl(int)) was much greater for the S-enantiomer than for the R-enantiomer.

Pharmacokinetics and efficacy of structurally related spirohydantoin and spirosuccinimide aldose reductase inhibitors.

1. Six potent aldose reductase inhibitors (ARI), three spirohydantoin (I to III) and three spirosuccinimide (IV to VI) compounds, showed similar IC50 activities in vitro for the inhibition of rat lens aldose reductase, but their ED50 values in diabetic rats varied as much as 20-fold in the lens and 50-fold in the sciatic nerve tissue. Pharmacokinetic studies were undertaken to investigate these findings.

Spiro[fluoreneisothiazolidin]one dioxides: new aldose reductase and L-hexonate dehydrogenase inhibitors.

The first examples of spiro[fluorene-9,4'- and -9,5'-isothiazolidin]one dioxides (1 and 2) were synthesized and screened for activity as aldose reductase and L-hexonate dehydrogenase inhibitors. Compared to compounds 1, and 9,5'-compounds 2, synthesized from fluorene-9-sulfonamides by alkylation at C(9) with ethyl bromoacetate followed by cyclization, were more active, but relatively nonselective, inhibitors of aldose reductase and L-hexonate dehydrogenase, with IC50 values for in vitro inhibition of both enzymes on the order of 10(-7)-10(-8) M. However, the isomeric 9,4'-compounds 1, prepared by alkylation of fluorene-9-carboxylic acid esters with bromo- or iodomethanesulfonamide followed by cyclization, were more selective inhibitors of L-hexonate dehydrogenase with IC50 values of about 10(-6) M.

Respiratory therapy as a component of an integrated hospital information system: the Parkland On-Line Information System (POIS).

Information handling is an important part of the activities of health care professionals, and the Parkland On-line Information System (POIS)--a computerized hospital information system--was established to more efficiently handle the processing and storage of information in our institution. Computerization of a respiratory therapy department is more effective if done in the context of a comprehensive, integrated hospital information system. Information and requests for services flow into the respiratory therapy departmental computer from other hospital terminals, and information, such as patient charges and statistical data, flow out of the departmental computer to those requesting such information.