Pharmacokinetic modeling of the high-dose bolus regimen of tirofiban in patients with severe renal impairment.

For the treatment of patients with acute coronary syndromes in the catheterization laboratory, a high-dose bolus (HDB) regimen of tirofiban (25 µg/kg bolus, followed by an infusion of 0.15 µg/kg/min) leads to a consistent and rapid inhibition of platelet aggregation during the first hour after initiation of therapy. The objective of the present study was to use pharmacokinetic modeling to identify an appropriate dosage of tirofiban that would produce a plasma concentration-time profile in patients with severe renal impairment (creatinine clearance<30 ml/min) as similar as possible to that of the HDB regimen in patients with normal renal function. For patients with severe renal impairment, previous recommendations have been to reduce the dosage by 50%. Pharmacokinetic modeling was performed with the following sets of data: the plasma concentrations of tirofiban from patients with normal renal function who were treated with the HDB regimen of tirofiban and the plasma concentrations of tirofiban from patients with severe renal impairment who were treated with a 0.1 µg/kg/min infusion of tirofiban for 1 h. In conclusion, for patients with severe renal impairment, a 25 µg/kg bolus, followed by a 0.10 µg/kg/min maintenance infusion of tirofiban produced a plasma concentration-time profile similar to that observed with the HDB regimen of tirofiban in patients with normal renal function.

Colorimetric sensor arrays for volatile organic compounds.

The development of a low-cost, sensitive colorimetric sensor array for the detection and identification of volatile organic compounds (VOCs) is reported. Using an array composed of chemoresponsive dyes, enormous discriminatory power is possible in a simple device that can be imaged easily with an ordinary flatbed scanner. Excellent differentiation of closely related organic compounds can be achieved, and a library of 100 VOCs is presented. The array discriminates among VOCs by probing a wide range of intermolecular interactions, including Lewis acid/base, Brønsted acid/base, metal ion coordination, hydrogen bonding, and dipolar interactions. Importantly, by proper choice of dyes and substrate, the array is essentially nonresponsive to changes in humidity.

Oxidative addition of Ph2TeCl2 to a dimethylplatinum(II) complex: effects of secondary bonding in the platinum-tellurium products.

In the first example of oxidative addition of tellurium-halide bonds to a transition-metal complex, Ph(2)TeCl(2) reacts with [PtMe(2)(bu(2)bpy)], 1, bu(2)bpy = 4,4'-di-tert-butyl-2,2'-bipyridine, to give an organoplatinum(IV) complex that can be formulated as an ionic diphenyl telluride complex [PtClMe(2)(TePh(2))(bu(2)bpy)]Cl or as a neutral chlorodiphenyltelluryl complex [PtClMe(2)(TePh(2)Cl)(bu(2)bpy)]; the complex contains an unusually long Te...Cl bond length of 3.43 A. The weakly bound chloride ligand is easily removed by reaction with AgO(3)SCF(3) to give the cationic complex [PtClMe(2)(TePh(2))(bu(2)bpy)](CF(3)SO(3)) in which the triflate anion is not coordinated to tellurium. This complex reacts with a second 1 equiv of AgO(3)SCF(3) to give the aqua complex [PtMe(2)(OH(2))(TePh(2)..O(3)SCF(3))(bu(2)bpy)](CF(3)SO(3)), in which a triflate anion forms secondary bonds with both the aqua and TePh(2) ligands. In these platinum(IV) complexes, the magnitude of the coupling constant (1)J(PtTe) is strongly influenced by the presence of the weakly bonded Te...X groups.

Synthesis of Metallacycles by Oxidative Addition of Sn-S, Sn-Se, Sn-Te, and Ge-Te Containing Precursors to Platinum(II).

The first metallacycles formed by oxidative addition of tin-sulfur, tin-selenium, tin-tellurium, and germanium-tellurium bonds to platinum(II) are reported. In particular, the ring compounds [(R(2)SnE)(3)], where R = Me, Ph and E = Se, Te, and the new compound [(Me(2)GeTe)(3)], react with [PtMe(2)(bu(2)bpy)] (bu(2)bpy = 4,4'-di-tert-butyl-2,2'-bipyridine) to give the new organoplatinum(IV) metallacycles [PtMe(2)(R(2)SnE)(2)(bu(2)bpy)] and [PtMe(2)(Me(2)GeTe)(2)(bu(2)bpy)], respectively. The tin-containing metallacycles complexes can undergo exchange of either the R(2)Sn or the E groups by reaction with [(R'(2)SnE)(3)] or [(R(2)SnE')(3)], respectively, to give the corresponding new metallacycles of general formula [PtMe(2)(R(2)SnE-R'(2)SnE)(bu(2)bpy)] or [PtMe(2)(R(2)SnE-R(2)SnE')(bu(2)bpy)]. The isostructural series of complexes [PtMe(2)(Ph(2)SnE)(2)(bu(2)bpy)] with E = S, Se, and Te have been characterized by X-ray structure determinations. It is shown that (119)Sn NMR is a useful method of structure determination for these metallacyclic compounds.