The bioequivalence of three different formulations of mefenamic acid was tested using the index zeta 2 previously defined by Rescigno. This index is a measure of the distance in Hilbert space of two concentration vs time functions; unlike the approach of Westlake which assumes a multiplicative model for the AUC and Cmax characteristics, this approach does not imply any hypotheses on the structure of the data and no particular model of the absorption or of the elimination processes. The index zeta 2 is simply an indication of how similar two formulations are. Results for this new test were compared with those obtained with two other tests, namely 90 and 95% symmetrical confidence intervals of Westlake and two one-sided t-tests of Shuirmann through the 90% confidence intervals in the ranges 80-125% for AUC and 70-143% for Cmax. Results of the new test are fully comparable with those obtained using the other two tests.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMedDate not supplied

On the stochastic theory of compartments. II. Multi-compartment systems.

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Body Fluids↗

PubMedDate not supplied

Some pharmacokinetic considerations about homeostatic equilibrium of endogenous substances.

Endogenous substances in the body are controlled through simple, very effective mechanisms, that preserve an optimum homeostatic equilibrium of baseline concentration and restore it when impaired. When planning a pharmacokinetic investigation of an endogenous substance exogenously administered, it is imperative to carefully ascertain the above mechanisms as well as the baseline value and their possible variations associated with daily rhythm, food, age, sex, menstrual cycle. Often the control mechanisms operate through non-linear processes, therefore a non-compartmental analysis or a tailored model may be more appropriate than the compartmental models used in standard pharmacokinetic analysis. Some specific examples of endogenous substances are discussed here on the basis of the data from the literature and personal experience.

Bile Acids and Salts↗

PubMedDate not supplied

Pharmacokinetics of endogenous substances: some problems and some solutions.

The paper deals with the most relevant aspects related to the pharmacokinetics of endogenous substances. Two different views are presented in order to focus on two aspects of the problem, the physiological background of these substances and the need for empirical or tailored models to process pharmacokinetic data. Very often endogenous substances follow saturable enzyme biotransformation, reversible interconversion, active and diffusional transports, renal threshold, endogenous synthesis plus dietary supply with possible balancement between these two factors, feedback processes, asymmetric distribution with specific body storage, and gender differences. These mechanisms allow the body to preserve and restore homeostatic equilibria of endogenous substances. The most relevant problem in pharmacokinetics of these substances is the presence of baseline concentration which needs to be carefully defined also for possible rhythms related to age, sex, diet, night and day periods. Theoretical considerations are presented for the management of pharmacokinetic analysis of these substances, which only rarely follow linear processes. Throughout the text various practical examples are considered.

Animals↗

PubMedDate not supplied

Fractionation and characterization of two forms of peroxidase from Oryza sativa.

Peroxidase (E.C. 1.11.1.7., hydrogen donor oxidoreductase) is widely distributed and has been isolated from many higher plants (1). The wide distribution of the enzyme suggests that it could be of great biological importance. However the role that it plays in metabolism is not clear due to the large number of reactions it catalyzes and the considerable number of isozymic species (2). In tomato plants, Evans and Aldridge (3) separated out six isoperoxidases and in a later paper Evans reported 12 isoperoxidases from tomato shoots (4). A homogeneous tomato fruit peroxidase isozyme was obtained by Jen et al. (5) using hydrophobic chromatography. Isozymes were not detected in Euphorbia characias peroxidase (6), in Ipomoea batatas peroxidase (7) and in Hordeum vulgare peroxidase (8). The simultaneous presence of Cu (II) amine oxidase and peroxidase in cell walls suggests that the peroxide generated on oxidation of the amines could be utilized by the peroxidase (6,8,9). In the graminea Oryza sativa, widely distributed, an FAD amine oxidase is present that oxidizes diamines (10). In this plant we also found two isoperoxidases called perox I and II. Only perox I was purified to homogeneity and its enzymatic, physical and chemical properties have been studied.

Chemical Fractionation↗

PubMedDate not supplied

Purification and characterization of an NAD(P)H:quinone oxidoreductase from Glycine max seedlings.

An NAD(P)H:(quinone acceptor) oxidoreductase (EC 1.6.99.2) was purified from Glycine max seedlings by means of chromatographic procedures. After 1371-fold purification, the enzyme showed a single band in IEF corresponding to an isoelectric point of 6.1. A single band was also found in native-PAGE both by activity staining and Coomassie brilliant blue staining. The molecular mass determined in SDS-PAGE was 21900 Da, while in HPLC gel-filtration it was 61000 Da. The NAD(P)H:quinone oxidoreductase was able to use NADH or NADPH as the electron donor. Among the artificial quinones which are reduced by this enzyme, 6-hydroxydopa- and 6-hydroxydopamine-quinone are of particular interest because of their neurotoxic effects.

2,6-Dichloroindophenol↗

PubMedDate not supplied

Observations of the dynamics of ionic potassium-38 in brain.

Short time course potassium dynamics in brain were investigated in the cat. 38K (T1/2 = 7.6m) was prepared on the BNL 60" cyclotron by the 40Ar(p, 3n)38K reaction. Positron decay in brain was measured by the limited angle of view positron camera (LAPC). Radioactivity corrected for physical decay following intravenous bolus injection of 38K showed an initial peak followed by a washout phase with a subsequent monotonic increase. The slope of the washout phase was linearly related to PaCO2 and the subsequent monotonic increase paralleled the arterial concentration of the tracer. No significant changes in 38K radioactivity were determined following coma producing levels of phenobarbital or seizure producing doses of potassium penicillin as compared to control.

Animals↗

PubMedDate not supplied

Flow graphs and tracer kinetics.

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Kinetics↗