The greatest allowed relative error in weights and threshold of strict separating systems.

An important consideration when applying neural networks is the sensitivity to weights and threshold in strict separating systems representing a linearly separable function. Perturbations may affect weights and threshold so that it is important to estimate the maximal percentage error in weights and threshold, which may be allowed without altering the linearly separable function. In this paper, we provide the greatest allowed bound which can be associated to every strict separating system representing a linearly separable function.

Antibacterial evaluation of a collection of norfloxacin and ciprofloxacin derivatives against multiresistant bacteria.

The objective of this study was to analyse an array of ciprofloxacin and norfloxacin derivatives in order to determine those with good activity against bacteria that already present fluoroquinolone resistance associated with mutations in the gyrA and/or parC genes. Four norfloxacin and 20 ciprofloxacin derivatives were synthesised and tested against quinolone-susceptible and -resistant Escherichia coli, Acinetobacter baumannii, Stenotrophomonas maltophilia and Staphylococcus aureus strains using a microdilution test. Among the derivatives, the 4-methyl-7-piperazine ciprofloxacin derivative showed a minimum inhibitory concentration for 50% of the organisms that was 16- and 8-fold lower than ciprofloxacin for A.

Activity-bioavailability balance in oral drug development for a selected group of 6-fluoroquinolones.

A nomogram is proposed to select the best candidate in drug development studies with quinolones and is intended to substitute other possible models. The nomogram is referred to as an activity-bioavailability balance (ABB) because it includes the following two criteria: ABB = [(1/gm MIC drug candidate)/ (1/gm MIC ciprofloxacin)].[(F(calc) drug candidate)/( F(calc) ciproflaxacin)].

Intrinsic absolute bioavailability prediction in rats based on in situ absorption rate constants and/or in vitro partition coefficients: 6-fluoroquinolones.

A preliminary study attempting to predict the intrinsic absolute bioavailability of a group of antibacterial 6-fluoroquinolones-including true and imperfect homologues as well as heterologues-was carried out. The intrinsic absolute bioavailability of the test compounds, F, was assessed on permanently cannulated conscious rats by comparing the trapezoidal normalized areas under the plasma concentration-time curves obtained by intravenous and oral routes (n = 8-12). The high-performance liquid chromatography analytical methods used for plasma samples are described.

Pharmacokinetics, bioavailability and absorption of flumequine in the rat.

The study demonstrates that the oral extent of bioavailability of flumequine in the rat, relative to the intravenous injection, is complete (0.94 +/- 0.04) and not significantly different from that found by the intraduodenal route (0.

Pharmacokinetics of liposome-encapsulated meglumine antimonate after intramuscular and subcutaneous administration in dogs.

Controlling canine leishmaniasis may reduce the incidence of human leishmaniasis, which affect immunocompromised persons, especially those with human immunodeficiency virus infection. Thus, the pharmacokinetics of liposome-encapsulated meglumine antimonate (LMA) in dogs was studied after intramuscular (I.M.

Structure-absorption relationships of a series of 6-fluoroquinolones.

The physicochemical constants and some structural parameters (topological, steric, and electronic) of eight third-generation monofluorate quinolones (six uncommercialized and two used clinically [ciprofloxacin and enrofloxacin]) were determined: pKa, intrinsic solubility (S0), chromatographic capacity factor, partition coefficient (P), valency molecular connectivity, molecular volume, molecular surface area, dipolar moment, and charges associated with each atom of the molecule. The apparent intestinal absorption rate constants (K(abs)) in rat (in vivo perfusion) and the MICs at which 90% of the isolates are inhibited (MIC90s) against 100 Escherichia coli strains were also determined. We sought to establish simple nonlinear and multiple linear correlations between K(abs), on the one hand, and lipophilic parameters and other physicochemical and structural parameters estimated.

Effects of ethanol on intestinal absorption of drugs. I. In situ studies with ciprofloxacin analogs in normal and chronic alcohol-fed rats.

The effect of chronic alcohol intake on the intestinal absorption of seven compounds belonging to a homologous series (ciprofloxacin derivatives) was evaluated using an in situ rat gut technique that measures the intrinsic absorption rates of the compounds both in control and chronic alcohol-fed rats. For chronic alcohol treatment, the animals were fed a liquid diet containing ethanol (36% of calories), whereas an isocaloric diet was given to the pair-fed control animals. The biophysical absorption model, relating the intestinal absorption rate constants and partition indexes of the tested compounds, was then established either for control or alcohol-fed animals.

Biophysical models as an approach to study passive absorption in drug development: 6-fluoroquinolones.

A preliminary study attempting to assess and explain the intestinal absorption of a series of antibacterial 7-piperazinyl-6-fluoroquinolones is presented. The synthesis, n-octanol partition coefficients, intrinsic rat gut in situ absorption rate constants, and in vitro antibacterial activity data found for these homologous compounds are described. A fluorimetric, reverse-phase HPLC method was performed for the quantification of the quinolones in absorption and partition samples.

Influence of the chromatographic capacity factor (log k') as an index of lipophilicity in the antibacterial activity of a series of 6-fluoroquinolones. Relationship between physico-chemical and structural properties and their hydrophobicity.

The aim of this study was to establish the influence of lipophilicity on the antibacterial activity (log 1/MIC50) of 22 fluoroquinolones and to assess the influence of their electronic, steric and topological properties on their hydrophobicity. The lipophilicity of the compounds, expressed as the chromatographic capacity factor (log k'), was determined by ion-pair reversed-phase HPLC. On the basis of the mathematical models developed, an attempt was made to confirm the mechanism of interaction of the quinolones with DNA-gyrase proposed previously.

Intestinal absorption of a series of 6-fluoquinolone derivatives: a comparative study.

The intestinal absorption rate constants of the five 6-fluoquinolones (norfloxacin, ciprofloxacin, pefloxacin, CNV 8802 and CNV 8804), have been estimated in the rat (n = 5) by means of an "in situ" intestinal perfusion method. Remaining 6-fluoquinol one concentrations in the perfusion liquid at fixed time (15, 30, 45, 60, 75, 90 and 120 minutes) were determined using a HPLC procedure with UV detection. Absorptions rate constants were estimated according to first order kinetics.