Absorption-time Profiles Research Articles

Influence of dissolution rate on the extent and rate of bioavailability of metoprolol

Abstract Three extended release formulations of metoprolol (95 mg metoprolol succinate) with different in vitro release rates were administered to ten healthy males (20–29 years) as single oral doses. The bioavailability properties of the three formulations were evaluated in relation to an intravenous dose (10 mg metoprolol tartrate) and an oral solution (95 mg metoprolol succinate). Both the rate and extent of metoprolol absorption were related to the drug release rate as shown by the plasma concentration-time profiles and resultant pharmacokinetic variables. Individual absorption-time profiles reflected well the corresponding in vitro release curves, showing a good correlation over the entire time interval for all three formulations. For the slowest formulations, drug absorption continued at very delayed times (24–30 h) in most individuals, confirming the good distal gastrointestinal absorption of metoprolol. A reduced bioavailability was seen with all extended release formulations compared with the solution and was probably caused by increased hepatic first-pass metabolism. Incomplete absorption may also contribute to the more markedly reduced bioavailability of the slowest formulation. Evaluation of compartmental (Wagner-Nelson, Loo-Riegelman) and noncompartmental (numerical deconvolution) methods for assessing drug absorption suggests that all three methodologies are appropriate when applied to extended release formulations of metoprolol.

ウサギに３種類の坐剤を投与した際のモルヒネの体内動態

We prepared three kinds of morphine suppositories: HE was based on the equivalent mixture of Witepsol H-15 and E-75; S was based on Witepsol S-55 alone; MSC contained controlled-release morphine tablet (MS Contin) in the same base as HE. The pharmacokinetics after rectal administration of the preparations was investigated in rabbits. We found that HE had short Tmax (10min) and that the sustained release continued around 6hr after administration. The extent of bioavailability (BA) of HE was 43.4%, and the plasma concentration of morphine was higher than orally administered MS Contin tablet, throughout the observation period. S had a high BA (95.1%) but Cmax (446.2ng/ml) was too high judged from some risk of adverse effect or dependence. Thus we considered it is not appropriate for clinical use. On the other hand, MSC had longer Tmax (150min). The plasma concentration 12hr after administration was around half the Cmax and the sustained release was found to be good. The MSC's BA also showed high value and only a little dispersion (78.3±6.6%). The cumulative absorption-time profiles of MSC in vivo approximated to the morphine-release behavior of MS Contin tablets in vitro.From the facts described above we conclude:1. We can expect the same or more analgesic effect from HE than oral MS Contin tablets.2. MSC is a good sustained-release morphine suppository which can be expected to be useful for cancer pain therapy, through every 12-hr administration.

Extension of the loo-riegelman method to pharmacokinetic data at steady state

The method of Loo and Riegelman is often used to calculate the relative amount absorbed as a function of time from plasma concentration data which follow a two-compartment open model. The method, however, is applicable only to single-dose data, whereas there is sometimes interest in the absorption-time profile at steady state after multiple doses. The method is modified here so that it can be applied to steady-state data and its use with a practical example is illustrated.

The formation of emitting CF 3 and CF 2 radical states by pulsed electron beam excitation

In electron irradiated argon/alkyl fluoride gas mixtures the quenching dynamics of argon transients and the kinetics of the UV and visible emission bands of electronically excited CF 2 and CF 3 radicals were investigated by the pulse radiolysis method. Assuming that these transient radical states are generated by a transfer of electronic excitation energy from the argon excited states to the admixed gases quenching rate constants of the argon species are obtained by numerical simulation of the experimentally obtained argon absorption time profiles as well the emission time curves of the alkyl fluoride transients. In comparison with photochemical measurements and as a result of kinetic calculations it could be concluded that the observed visible emission band around 600 nm was due to transitions of CF 3 radical states, where the UV emission spectra between 230 and 370 nm represents mainly CF 2 radical transitions. In the case of C 2F 6 the transfer from argon dimer states resulted in a contribution to the CF 3 fluorescence around 600 nm. In all other investigated systems only the atomic states Ar(4 s) were the precursers of the emitting alkyl fluoride species. The collision free lifetime of CF 2 wasestimated by studying the UV-fluorescence decay in pure alkyl fluorides as a function of pressure and the fluorescence lifetime of CF 3 was obtained as a result of the numeric fluorescence analysis.

Kinetics of evaporation and decomposition of isopropyl nitrate by rapid scan IR spectroscopy

The evaporation and chemical decomposition kinetics of IPN were investigated at 200, 225 and 250°C by monitoring the gas phase using rapid scan FTIR spectroscopy. Evaporation and decomposition rates were determined by a fit of a special model to the experimental absorption-time profiles. The model combines elements of the quasi-static theory and simple chemical reaction kinetics.

The u.v. and visible emission bands of CF 3 radicals produced by pulsed electron beam excitation

Using time-resolved optical spectroscopy the kinetics of the u.v. and visible emission bands of electronically excited CF n ( n = 2,3) radicals were investigated by the pulse radiolysis method. In rare gases used as energy absorbing media, atomic and molecular transients which transfer their energy to foreign gases were formed by electron irradiation. In the presence of CF 3H, C 2F 6, C 3F 8 and CF 4 the decay of the absorption of the Ar(4s) as well as the Ar 2( 3Σ +) states and the growth of the Ar 2( 3Σ +) become faster. As, e.g. the argon absorption bands were influenced by the admixtures, new emission bands were obtained due to electronic transitions of excited CF 2 and CF 3 radicals in the spectral range 200–700 nm. Assuming that the emissions are generated by a transfer of electronic excitation energy from the rare gas excited states to the admixed gases, in which CF 2 and CF 3 radicals are formed by dissociation reactions, rate constants of the quenching reaction of the rare gas atomic and molecular states are obtained by numerical simulation of the experimental absorption time profiles. Collision free life-times of the emitting states were observed from simulations of the alkyl fluoride fluorescence decays as a function of the solute concentration.

Intramolecular hydrogen transfer in the o-tolyl radical studied by time resolved absorption measurements

The intramolecular hydrogen transfer rate of o-tolyl radicals has been examined by monitoring the absorption time profile of benzyl radicals formed in the picosecond 266 nm laser photolysis of o-chlorotoluene. The rise time of the benzyl radical absorption, 6.5 ns, was attributed mostly to the rearrangement rate of o-tolyl radicals to benzyl radicals.

Decomposition rate of benzyl chloride excited at 266 nm in the vapor phase

Picosecond laser photolysis of benzyl chloride vapor has been examined by monitoring the absorption time profile of benzyl radicals formed in the 266 nm photodecomposition. The rise time of benzyl radical absorption 6 ns was attributed to the decomposition rate of benzyl chloride molecules under collision free conditions.

Excited singlet state kinetics on a subnanosecond time-scale

It is possible to study directly the absorption time-profiles of short-lived excited singlet states by sampling the transient excitation spectra for fluorescence from upper states. This approach has many advantages over direct absorption measurements, since the effects of triplet state absorption can be suppressed and the population time-profiles of excited singlet states can be studied in detail. The first direct measurements are reported of singlet state absorption time profiles in a number of aromatic aza- and carbonyl compounds.

Analysis of the time-profiles of transient absorption observed in the kinetic spectrophotometry of aromatic hydrocarbons

The transient absorption time-profiles observed in the laser photolysis of benzenoid aromatic hydrocarbons are analysed in terms of the well established transition mechanisms for these molecules, and the theoretical and experimental traces are compared. The effects of fluorescence and ground state absorption on the time profile are considered, and the importance of fluorescence corrections is demonstrated for the case of 1,12 benzperylene.

Thermische Zerfallsreaktionen von Nitroverbindungen in Stosswellen. III: Dissoziation von 1‐Nitropropan und 2‐Nitropropan

AbstractThe pyrolysis of 1‐ and 2‐nitropropane highly diluted in Ar has been studied in shock waves at temperatures K 915 < T < 1200 K and total gas concentrations 7 · 10−6 mol cm−3 < [Ar] < 1.5 · 10−4 mol cm−3. The reactions behind the shock waves have been followed by recording light absorption‐time profiles of the decomposing molecules and the produced NO2 Under the conditions of the experiments, the primary reaction step in both cases is the CN bond:fission: \documentclass{article}\pagestyle{empty}\begin{document}$ \begin{array}{rcl} {\rm 1} - {\rm C}_{\rm 3} {\rm H}_{\rm 7} {\rm NO}_{\rm 2} {\rm (} + {\rm M)} &\to & n - {\rm C}_{\rm 3} {\rm H}_{\rm 7} + {\rm NO}_{\rm 2} {\rm (} + {\rm M)\quad k} = 2.3 \cdot 10^{15} {\rm exp }(- 55{\rm kcal mol}^{ - 1} /{\rm RT}){\rm s}^{ - 1} \\ 2 - {\rm C}_{\rm 3} {\rm H}_{\rm 7} {\rm NO}_{\rm 2} {\rm (} + {\rm M)} &\to & i - {\rm C}_{\rm 3} {\rm H}_{\rm 7} + {\rm NO}_{\rm 2} {\rm (} + {\rm M)\quad k} = 2.4 \cdot 10^{15} {\rm exp }(- 54{\rm kcal mol}^{ - 1} /{\rm RT}){\rm s}^{ - 1} \\ \end{array} $\end{document} (first order rate constants k measured at concentrations of [Ar] ≃ 10−4 mol cm−3).At these concentrations the reactions are near to the high pressure limit. By varying the Ar‐concentrations over one order of magnitude, only a slight pressure dependence was found. Reaction mechanisms which account for NO2 removal are discussed.

A study of the relationship between absorption-time profiles of polar-cap-absorption events and Forbush decreases of cosmic-ray intensity

Forbush decrease data recorded by neutron monitors during PCA events support the interpretation of the absorption-time profiles of PCA events as due to solar particles under the influence of magnetic fields carried by solar plasma. All PCA events showing evidence of strong trapping of solar particles are accompanied by strong Forbush decreases, the magnitudes of which are a function of the delay time from flare to SC storm. Those PCA events showing little evidence of trapping are accompanied by only very weak decreases. The large western excess of these latter events is explained in terms of sun-earth magnetic linkage set up by earlier flare activity. The relative merits of two models of the interplanetary fields are examined. (auth)