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.     

Vibrational analysis and conformational studies of allylamine

Infrared absorption spectra of allylamine and its amino-deuterated species were observed in the gas phase and in the low-temperature Ar matrix. An analysis of the spectra showed that there exist mainly three rotational conformers, and possibly one other conformer as a minor component. At room temperature, the skew forms around the CC bond populate about 70%, while the rest are assigned to the cis form(s). On the other hand, two forms around the CN bond, gauche and trans, exist with about equal populations.     

Tight inclusion of an acid guest into the cavity of cyclodextrin bearing an amino moiety in dimethyl sulfoxide

Circular dichroism measurements show that β-cyclodextrin with an amino moiety has a strong binding ability for ferrocenecarboxylic acid in dimethyl sulfoxide via an acid-base interaction.     

Influence of polyvinylalcohol on the solvation volumes of FeCl<Subscript>3</Subscript> and CoCl<Subscript>2</Subscript> in aqueous ethanol solutions

The effect of polyvinylalcohol (PVA) on molar, Van-der Waals and the electrostriction volumes of FeCl₃ and CoCl₂ in pure H₂O and 50% ethanol (EtOH)–water mixtures was studied. Excess volumes were also calculated and their values were discussed in terms of Pierotti theory (Scaled Particle Theory). Different theoretical energy values were calculated to explain the following parameters: volumes, dispersion, induction energies and 6-12 Lennard–Jones parameters. The increase and the decrease in excess volumes of FeCl₃, CoCl₂ in the absence and in the presence of polyvinyl alcohol in both aqueous and 50% EtOH–H₂O mixtures were also discussed in terms of the increase or decrease of different interaction energies.     

On the construction of [q 4 + q 2 − q, 5,q 4 − q 3 + q 2 − 2q; q]-codes meeting the Griesmer bound

It is unknown whether or not there exists an [87, 5, 57; 3]-code. Such a code would meet the Griesmer bound. The purpose of this paper is to give a constructive proof of the existence of [q ⁴ + q ² – q, 5, q ⁴ – q ³ + q ² – 2q; q]-codes for any prime power q 3. As a special case, it is shown that there exists an [87, 5, 57; 3]-code with weight enumerator 1 + 156z ³⁷ + 82z ⁶⁰ + 2z ⁶³ + 2z ⁷⁸. The new construction settles an open problem due to Hill and Newton [10].     

Electron transfer reaction in a single protein molecule observed by total internal reflection fluorescence microscopy

To observe an electron transfer (ET) process in a single protein molecule, we constructed a model system, Alexa-HCytb5, in which cytochrome b5 (Cytb5) is modified with a fluorescent probe, Alexa Fluor 647 dye. In this model system, intramolecular transfer of an electron from the Alexa dye to heme in Cytb5 is supposed to oxidize the probe and quench its fluorescence, and the ET reaction at the single-molecule level can be monitored as the intermittent change in the fluorescence intensity. Alexa-HCytb5 was fixed on the glass surface, and illumination of laser light by the total internal reflection resulted in blinking of the fluorescence from the single Alexa-HCytb5 molecule in the time scale of several hundred milliseconds. Each Alexa-HCytb5 molecule is characterized by its own rate constant of the blinking, corresponding to the ET rate constant at the single-molecule level, and its variation ranges between 1 and 10 s(-1). The current system thus enables us to visualize the ET reaction in the single protein molecule, and the protein ET reaction was found to be explained by the distribution of the rate constants. On the basis of the Marcus theory, we suggest that the origin of this rate distribution is the distance change associated with the structural fluctuation in the protein molecule.