No abstract

Some phenyl azo hydroxynaphthalene dyes (e.g., sunset yellow) are certified as approved colorants for food, cosmetics, and drug formulations. The hydrophobicity of 4 newly synthesized azo dyes of the phenyl azo hydroxynaphthalene class was investigated, as a training set, with the goal of developing models for quantitative structureproperty relationships (QSPR). Retention behavior of the molecules reversed-phase thin-layer chromatography (RPTLC) was investigated using liquid paraffin-coated silica gel as the stationary phase. Mobile phases consisted of aqueous mixtures of methanol, acetone, and dimethylformamide (DMF). Basic hydrophobicity parameter (Rmw), specific hydrophobic surface area (S), and isocratic chromatographic hydrophobicity index (o) were computed from the chromatographic data. The hydrophobicity index (Rm) decreased linearly with increasing concentration of organic modifiers. Extrapolated Rmw values obtained by using DMF and acetone differ significantly from the value obtained by using methanol as organic modifier P < 0.05, 1-way analysis of variance (ANOVA), Tukey's multiple comparison test. Structureproperty relationships showed that hydrophobicity was dependent on type and position of naphthalene ring substituents. Rm decreased with the presence of a highly polar substituent (e.g., COOH). Owing to intramolecular interaction, Rm increased when the common hydroxyl group (OH) is positioned ortho to the azo group, relative to para positioning, in 2 positional isomers. Pattern recognition data analysis underscores the utility of φo as a more accurate hydrophobicity descriptor than Rmw. φo is negatively correlated with theoretically calculated density, surface tension, and refractive index for the molecules. These models could be used to predict toxicity (absorption, distribution, metabolism, excretion, toxicity; ADMET) properties of the azo dyes and may also play useful roles in computer-assisted molecular discovery of nontoxic azo dyes.

IntroductionThe co-existence of malaria with bacterial infections is common in the tropics, hence the concurrent use of antimalarials and antibiotics.ObjectiveThis study aimed to investigate the effect on pharmacokinetics and antimicrobial activity of co-administration of quinine and combined ampicillin–cloxacillin.MethodsIn total, 14 healthy adults received single oral doses of ampicillin–cloxacillin combination alone and with quinine in a randomized crossover manner. Urine samples collected at predetermined intervals over 48 h were analysed. The effect of quinine on minimum inhibitory concentrations (MICs) of ampicillin and cloxacillin were determined against Staphylococcus aureus by agar diffusion, agar dilution, and broth dilution.ResultsQuinine significantly reduced the rate and extent of excretion of ampicillin and cloxacillin (p < 0.0002). The total amounts of ampicillin and cloxacillin excreted unchanged (Du∞) alone were 217.10 ± 53.82 and 199.0 ± 64.29 mg versus 126.40 ± 50.63 and 135.20 ± 52.24 mg, respectively, with quinine. Respective maximum excretion rates (dDu/dtmax) for ampicillin and cloxacillin were 43.55 ± 19.41 and 77.64 ± 29.65 mg/h alone versus 18.01 ± 8.52 and 53.16 ± 20.72 mg/h with quinine. This indicates a significant reduction in Du∞and dDu/dtmax by 41.78 and 58.65 % for ampicillin and 32.06 and 31.53 % for cloxacillin. Conversely, the disposition of quinine was unaffected by ampicillin–cloxacillin (p > 0.1). The MIC of antibiotics alone versus with quinine, respectively, were 0.11 ± 0.04 and 0.78 ± 0.1 µg/ml for ampicillin, and 0.18 ± 0.1 and 0.92 ± 0.4 µg/ml for cloxacillin, with a five- to sevenfold increase (p > 0.01); indicating a decrease in antimicrobial activity by quinine.Conclusions Quinine therefore, reduced the bioavailability and the antimicrobial activity of ampicillin–cloxacillin upon co-administration, which may have therapeutic implications. Caution is required with the co-administration of these medicines.

These pharmacokinetic values indicate slowed and diminished absorption (bioavailability) of Clox when concurrently administered with PG. The clinical implication is unknown. However, concomitant administration of the two drugs during antibacterial therapy should be done with caution so as to avoid subtherapeutic levels of Clox, which can lead to treatment failure and facilitate drug resistance.

Co-administration of halofantrine and kolanut caused a significant decrease in the plasma concentrations of halofantrine and the active metabolite desbutylhalofantrine probably during adsorption of the drug due to complex formation. This indicates that caution should be exerted when the drug is taken together with caffeine-containing nutrients.