Tetraanionic organoborate squares glued together by cations to generate nanotubular stacks.
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Biomedical subjects
Publications and source records attributed to Richard Robson.
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This open-label, single-period study evaluated the single-dose pharmacokinetics of ezetimibe (EZE) 10 mg in the setting of steady-state cyclosporine (CyA) dosing in renal transplant patients. A single 10-mg dose of EZE was coadministered with the morning dose of CyA (75-150 mg twice a day). Total EZE (sum of unconjugated, parent EZE and EZE-glucuronide; EZE-total) AUC(0-last) and Cmax were compared to values derived from a prespecified database of healthy volunteers. Geometric mean ratios (90% CIs) for (EZE + CyA)/EZE alone for EZE-total AUC((0-last)) and Cmax were 3.41 (2.55, 4.56) and 3.91 (3.13, 4.89), respectively. Compared to healthy controls, EZE-total AUC((0-last)) was 3.4-fold higher in transplant patients receiving CyA; similar exposure levels were seen in a prior multiple-dose study in which EZE 50 mg was administered to healthy volunteers without dose-related toxicity. Because the long-term safety implications of both higher EZE exposures and undetermined effect on CyA are not yet understood, the clinical significance of this interaction is unknown.
Reaction between boric acid and guanidinium salts in methanolic solution at room temperature in the presence of various bases and anions gives well-formed solvated crystals of composition {[B(OCH3)4]3[C(NH2)3]4}+X-. The products in which X- = Cl- and PF6- are characterized by single-crystal X-ray diffraction. The tetramethoxyborate and guanidinium components form a highly symmetrical (cubic) hydrogen-bonded 3D network having the "boracite topology" [i.e., the (63)(6284) topology]. Highly disordered solvent molecules and anions occupy methyl-surfaced cavities and channels that represent more than 30% of the space.
AIMS: To compare the pharmacokinetics of oseltamivir and oseltamivir carboxylate in hepatically impaired patients and healthy subjects. METHODS: Hepatically impaired patients (n = 11) and healthy subjects (n = 11) were individually paired on the basis of gender, age (+/-10 years) and body weight (+/-20%) and administered a single dose of oseltamivir (75 mg). RESULTS: Oseltamivir and oseltamivir carboxylate C(max) were < or =6% and < or =19% lower, and their AUC(0,infinity) 33% higher and < or =19% lower, respectively, in hepatically impaired patients compared with healthy subjects. These changes are within the safety limits for the drug. CONCLUSIONS: The metabolism of oseltamivir is not compromised [corrected] in hepatically impaired patients. No dose adjustment is required in these patients when receiving oseltamivir.
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Aqueous reaction mixtures containing dihydroxyfumaric acid, M2+ (M = Zn, Co, Fe, and Mg) and acetate ion at room temperature give crystals, suitable for single-crystal X-ray diffraction studies, of composition [(MII)8(C4O7)4(H2O)12].24H2O, in which the C4O74- component is the alkoxide-tricarboxylate tetra-anionic species -OC(CO2-)3, a new oxyanion of carbon. All four compounds crystallize in the body-centered space group I3m with cell dimensions a approximately 15.0 A. Discrete electrically neutral [(MII)8(C4O7)4(H2O)12] molecules are present, with a cubane-like core consisting of four trigonal prismatic metal centers and four mu3-alkoxo bridges from separate -OC(CO2-)3 ligands. The octametallic molecule is highly symmetrical, with four fac tri-aqua octahedral metal centers tetrahedrally appended to the central cubane-based [(MII)8(C4O7)4 ]8- unit. The molecules assemble in the crystal in a body-centered cubic fashion, each being attached to its eight neighbors by 24 equivalent hydrogen bonds-an extreme example of self-complementarity.
Addition of Co(NH3)6(3+) to aqueous solutions of Cu(II) in excess carbonate promotes the assembly of a new highly charged carbonato-copper(II) anion, [Cu4(OH)(CO3)8](9-), which contains an unusual mu4 hydroxo-bridged square Cu4 arrangement, stabilised in the crystal by no less than forty hydrogen bonds (< 3 Angstrom) to hexammine cations.
The serendipitous discovery of a 3D [Cu(CO(3))(2)(2-)](n) network with the topology of the 4(2)6(4) sodalite net in [Cu(6)(CO(3))(12)(CH(6)N(3))(8)].K(4).8H(2)O paved the way for the deliberate engineering of an extensive series of structurally related guanidinium-templated metal carbonates of composition [M(6)(CO(3))(12)(CH(6)N(3))(8)]Na(3-)[N(CH(3))(4)].xH(2)O, where the divalent metal M in the framework may be Mg, Mn, Fe, Co, Ni, Cu, Zn, or Cd. A closely related crystalline material with a [Ca(CO(3))(2)(2-)](n) sodalite-like framework, but containing K(+) rather than Na(+), of composition [Ca(6)(CO(3))(12)(CH(6)N(3))(8)]K(3)[N(CH(3))(4)].3H(2)O was also isolated. All of these compounds were obtained under the simplest possible conditions from aqueous solution at room temperature, and their structures were determined by single-crystal X-ray diffraction. Pairs of guanidinium cations are associated with the hexagonal windows of the sodalite cages, alkali-metal cations are associated with their square windows, and N(CH(3))(4)(+) ions are located at their centers. Structures fall into two classes depending on the metal, M(II), in the framework. One type, the BC type (Im3m), comprising the compounds for which M(2+) = Ca(2+), Mn(2+), Cu(2+), and Cd(2+), has a body-centered cubic unit cell, while the second type, the FC type (Fd3c), for which M(2+) = Mg(2+), Fe(2+), Co(2+), Ni(2+), and Zn(2+), has a face-centered cubic unit cell with edges on the order of twice those of the BC structural type. The metal M in the BC structures has four close carbonate oxygen donors and four other more distant ones, while M in the FC structures has an octahedral environment consisting of two bidentate chelating carbonate ligands and two cis monodentate carbonate ligands.
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Reaction of Ag(tcm), tcm = tricyanomethanide, C(CN)(3)(-), with a range of terminal and bridging ligands results in formation of a series of new coordination polymers. Recrystallization of Ag(tcm) from acetonitrile generates Ag(tcm)(MeCN), which is composed of corrugated (6,3) sheets displaying two-fold 2D --> 2D parallel interpenetration and is topologically identical to the parent Ag(tcm) structure. Ag(tcm)(L) species, L = 1,4-diazobicyclo-[2.2.2]-octane (dabco) or 4,4'-bipyridine (bipy), contain two interpenetrating 3D networks composed of 3-connecting (tcm) and 5-connecting (Ag) centers. The structure of Ag(tcm)(bpe), bpe = 1,2-bis(4-pyridyl)ethene, contains 1D ladderlike polymers connected by weak Ag-tcm interactions into two interpenetrating 3D nets. Ag(tcm)(Mepyz)(3/2), Mepyz = methylpyrazine, also contains 1D ladders, while Ag(tcm)(Me(4)pyz)(1/2), Me(4)pyz = tetramethylpyrazine, contains 2D sheets composed of Ag(tcm) 1D "tubes" linked by bridging Me(4)pyz ligands. Ag(tcm)(hmt), hmt = hexamethylenetetramine, has a 3D network structure in which the hmt ligands are 3-connecting, the tcm anions are 2-connecting, and the silver atoms are 5-connecting. The topology is the same as displayed by Ag(tcm)(L), L = dabco or bipy.
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BACKGROUND: These studies were conducted to determine whether bivalirudin clearance and pharmacodynamics are dependent on dose, renal function, or gender. METHODS: Two studies were performed. The first comprised 25 patients who were undergoing percutaneous coronary intervention-8 with normal renal function, 11 with mild renal impairment, and 6 with moderate renal impairment. Each patient received a bolus dose of bivalirudin (1 mg/kg) followed by an infusion (2.5 mg/kg per hour for 4 of 6 hours, then 0.5 mg/kg per hour for 4 of 6 hours). The second study enrolled 8 volunteers with severe renal impairment who received a bivalirudin bolus of 1 mg/kg, followed by an infusion of 0.5 mg/kg per hour for 10 hours. Bivalirudin in plasma and urine was assayed with a newly developed, highly specific liquid chromatography-mass spectrometry assay. RESULTS: Clearances at the two infusion doses did not differ significantly (3.23 mL/min per kilogram and 3.16 mL/min per kilogram). There was no statistically significant difference in area under the concentration-time curve (AUC) and in plasma clearance between patients with normal renal function and those with mild renal impairment. Patients with moderate and severe renal impairment had reductions in plasma clearance of 21% and 24%, respectively. The level of anticoagulation(activated clotting time) was similar between groups. There was no difference between male and female patients. CONCLUSION: The clearance of bivalirudin is dependent on renal function but independent of dose and gender. Approximately 20% of unchanged drug is cleared via the kidney, and the remainder presumably undergoes proteolysis intracellularly. The pharmacodynamics of bivalirudin are dose-dependent and gender-independent. Bivalirudin kinetics are linear in the dose ranges that are used in percutaneous coronary intervention and that are under investigation for use in acute coronary syndromes.
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