The pharmacokinetics of coumarin (C) upon i.v. and p.o. administration and its metabolites 7-hydroxy-coumarin (7-HC) and 7-hydroxy-coumarin glucuronide (7-HCG) have been studied. Six healthy volunteers were involved in this investigation. Four of the volunteers participated in a crossover study. Coumarin was administered i.v. and p.o. in dose sizes of 0.25 mg/kg and 0.857 mg/kg, respectively. Coumarin is rapidly absorbed p.o., however the availability to systemic circulation is less than 4%. The rest of the dose appears quantitatively as 7-HC and 7-HCG in systemic circulation suggesting an extensive firstpass effect. Coumarin and 7-HCG are best fitted to an open two-compartment model, whereas 7-HC is best fitted to an open one-compartment model. The biological half-life of both C (0.80 vs. 1.02 h) and 7-HCG (1.47 vs. 1.15 h) was not significantly different for the two routes of administration. The large total clearance of C again suggests a first-pass effect; while that of 7-HCG, which is nearly exclusively eliminated into urine, indicates active tubular secretion of the glucuronide.

We have given single high doses of dexamethasone phosphate by intravenous infusion as an antiemetic to 15 cancer patients receiving regimens containing cisplatin and/or doxorubicin. The patients received graded doses of dexamethasone phosphate, in the range 40-200 mg, dependent upon nausea and vomiting scores, during up to three consecutive cycles of cancer chemotherapy. Plasma and urine concentrations of dexamethasone (dexamethasone alcohol) were measured by HPLC. The plasma concentration - time data were described by an open two-compartment model. The pharmacokinetic variables were independent of the dose of dexamethasone over the range studied. The terminal half-time was 4.0 +/- 0.4 h and the total body clearance was 3.5 +/- 0.4 ml X min-1 X kg-1. The volume of the central compartment and the total apparent volume of distribution were 0.23 +/- 0.03 and 1.0 +/- 0.1 l X kg-1 respectively. Approximately 8% of the dose was excreted into the urine as dexamethasone.

The o-aminophenol-N,N,O-triacetic acid (APTRA) chelator is employed extensively as a metal-recognition moiety in fluorescent indicators for biological free Mg(2+), as well as in low-affinity indicators for the detection of high levels of cellular Ca(2+). Despite its widespread use in sensor design, the limited metal selectivity of this chelating moiety can lead to binding of competing cations that complicate the fluorescence-based detection of metals of interest in complex samples. Reported herein are the structural characterization of APTRA complexes with various biologically relevant cations, and the thermodynamic analysis of complex formation with Mg(2+), Ca(2+) and Zn(2+). Our results indicate that the low affinity of APTRA for Mg(2+), which makes it a suitable metal-recognition moiety for sensitive analysis of typical millimolar levels of this metal in cells, stems from a much higher enthalpic cost of Mg(2+) binding compared to that of other cations. The results are discussed in the context of indicator design, highlighting the aspects that may aid the future development of fluorescent sensors with enhanced metal selectivity profiles.

The use of tetrafluoroethylene (TFE) in academic institutions beyond a few millimoles has often been inhibited by the compound's inherent danger and general lack of commercial availability. On the other hand, TFE is prepared industrially on a rather large scale by a number of major fluorochemical companies via the pyrolysis of chlorodifluoromethane at high temperatures, yielding TFE and HCl. For a few years at The University of Alabama and Clemson University, we have been preparing TFE on a 100 +-gram scale by the pyrolysis under dynamic vacuum of pentafluoropropionate salts, which can be obtained from the neutralization of pentafluoropropionic acid with a M(OH) n (where M = Li, Na, K, and Cs for n = 1 and Mg, Ca, and Ba for n = 2). Additionally, potassium pentafluoropropionate can be prepared from the reaction of potassium trimethylsilanolate and ethyl pentafluoropropionate. The pentafluoropropionate salts and their