Interspecies differences in pharmacokinetics of an antiallergic agent, 1-(2-ethoxyethyl)-2-(hexahydro-4-methyl-1,4-diazepin-1-yl) benzimidazole difumarate (KG-2413) after intravenous administration to rats, guinea pigs and dogs

Interspecies differences in the pharmacokinetics of an antiallergic agent, 1-(2-ethoxyethyl)-2-(hexahydro-4-methyl-1,4-diazepin-1-yl)benzimid azole difumarate (KG-2413) after intravenous administration were investigated in rats, guinea pigs and dogs. The disappearance of unchanged KG-2413 base was described by biexponential curves in all three animal species. The areas under the plasma concentration-time curves (AUC) in rats, guinea pigs and dogs were 218, 421 and 369 ng.h/ml, respectively, at a dose of 2 mg/kg. The volume of distribution in rats was comparable to that in dogs, and was about three times greater than that in guinea pigs. This might be due to the difference in the unbound fractions of KG-2413 base in plasma (fu), that is, the values of fu in rats, dogs and guinea pigs were 0.607, 0.603 and 0.189, respectively. The first-order elimination rate constant from the central compartment (kcl) in dogs were smaller than those in rats and guinea pigs. Total body clearances (CLtot) of KG-2413 base in rats and guinea pigs were comparable to the hepatic blood flow rate (Q) of each animal. Assuming that KG-2413 base is only eliminated in the liver, relatively rapid metabolism of KG-2413 base occurred in the liver of rats and guinea pigs. In dogs, extrahepatic elimination was suggested because the value of CLtot seemed to be greater than that of Q.     

Statistical mechanics of thermal diffusion

Expressions of the flows of atoms A and B of a binary system in a crystal are derived as the response to the imposed gradients of temperature and chemical potentials. The formulation is done using the pair approximation of the Path Probability Method of irreversible statistical mechanics and atomic migration is assumed to be via the vacancy mechanism. The energy carried by photons (and electrons) under the temperature gradient is assumed to be independent of the atomic flux. For the case near equilibrium, linear relations are derived among the atomic fluxes, the energy flux (associated with atomic flux) and the gradients. The Onsager reciprocal relations are proved to hold among the coefficients, including those related to energy flows. The heat of transport (energy carried by a diffusing atom) and the heat conduction due to atomic flux are thus unambigously derived.     

Quasifinite highest weight modules over the superW 1+∞algebra

We study quasifinite highest weight modules over the supersymmetric extension of theW ₁₊ algebra on the basis of the analysis by Kac and Radul. We find that the quasifiniteness of the modules is again characterized by polynomials, and obtain the differential equations for highest weights. The spectral flow, free field realization over the (B, C)-system, and the embedding into (|) are also presented.Address after April 1, 1994: Research Institute for Mathematical Sciences, Kyoto University, Kyoto 606, JapanAddress after April 1, 1994: Uji Research Center, Yukawa Institute for Theoretical Physics, Kyoto University, Uji 611, Japan     

Cross-coupling of benzylic acetates with arylboronic acids: one-pot transformation of benzylic alcohols to diarylmethanes

Benzylic acetates reacted with arylboronic acids in the presence of a DPEphos-[Pd(eta3-C3H5)Cl]2 catalyst when tert-amyl alcohol was used as a solvent, and the catalytic cross-couplings produced diarylmethanes in high yields (up to 94% isolated yield).     

Determination of 1-hydroxypyrene in human urine by high-performance liquid chromatography with fluorescence detection using a deuterated internal standard

A high-performance liquid chromatographic method has been developed for the quantification of 1-hydroxypyrene (1-OHP) in human urine using deuterated 1-hydroxypyrene ([2H9]1-OHP) as an internal standard with fluorescence detection. [2H9]1-OHP was prepared enzymatically from deuterated pyrene ([2H10]Pyr) with cytochrome P450 1A1. It eluted immediately prior to non-deuterated 1-OHP on alkylamide-type reversed-phase columns and had nearly the same fluorescence characteristics as non-deuterated 1-OHP. The detection limit was 0.1 microg/L and the calibration range was from 1 to 100 nmol/L. Urine sample treatment involved enzymatic hydrolysis followed by solid-phase extraction using Sep-Pak C18 cartridges. The proposed method was used to determine urinary 1-OHP in smokers and non-smokers.     

Inequalities for a distribution with monotone hazard rate

Summary LetX be a positive random variable with the survival function and the densityf. LetX have the moments μ=E(X) and μ₂=E(X ²) and put ε=|1-μ₂/2μ²|. Put and . It is proved that the following inequalities hold: , for allx>0, ifq(x) is monotone and that , ifq ₁ (x) is monotone. It is also shown that Brown's inequality which holds wheneverq ₁ (x) is increasing is not valid in general whenq ₁ is decreasing. The Institute of Statistical Mathematics     

Selective syntheses of metalated pyridines from two different unsymmetrical acetylenes, a nitrile, and a titanium(II) alkoxide

Cyclotrimerization of two different, unsymmetrical acetylenes and p-toluenesulfonylnitrile with a divalent titanium alkoxide reagent, Ti(O-i-Pr)4/2 i-PrMgCl, yielded single pyridyltitanium compounds in a highly selective manner. These metalated pyridines were confirmed by deuteriolysis to give the corresponding deuterated pyridines and underwent iodinolysis and copper-catalyzed alkylation to demonstrate their synthetic utility. Alternatively, a different type of cyclotrimerization of an alkynamide, terminal acetylenes, and alpha-alkoxynitriles mediated by the same titanium(II) alkoxide again proceeded in a highly selective manner to give single pyridines having a titanated side chain.     

The autorecycling oxidation of benzylamine by synthetic 8-hydroxy-5-deazaflavin derivatives

Various 8-hydroxy-5-deazaflavin derivatives were synthesized as the model compounds of coenzyme F₄₂₀-These compounds oxidized benzylamine to benzaldehyde more efficiently than the corresponding 8-unsubstituted 5-deazaflavins.