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Introduction: The co-existence of malaria with bacterial infections is common in the tropics, hence the concurrent use of antimalarials and antibiotics., Objective: This study aimed to investigate the effect on pharmacokinetics and antimicrobial activity of co-administration of quinine and combined ampicillin-cloxacillin., Methods: In 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., Results: Quinine 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/dt max) 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/dt max 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.

Ampicillin exhibited a negative and a positive cotton effects on the circular dichroism (CD) spectra in the wavelength range of 200-280nm. Cloxacillin showed a positive cotton band peaking at 228nm. Three sensitive, precise and accurate CD spectroscopic methods have been developed for the determination of ampicillin and cloxacillin. Method A was used for the determination of ampicillin in presence of cloxacillin by measuring ellipticity at 206nm. Method B and C were employed to determine ampicillin and cloxacillin based on evaluation of ellipticity at 233nm and 228nm, respectively. Methods A, B and C showed linearity in the concentration range of 10-40μgmL(-1), 5-40μgmL(-1) ampicillin and 10-80μgmL(-1) cloxacillin, respectively. The method A was successfully applied to the determination of ampicillin in commercial dosage forms containing equivalent amount of cloxacillin., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Ampicillin and cloxacillin were degraded together under different stress test conditions prescribed by International Conference on Harmonization. The samples so generated were used to develop a stability-indicating high performance liquid chromatographic (HPLC) method for the two drugs. The drugs were well separated from degradation products using a reversed-phase (C-18) column and a mobile phase comprising of acetonitrile:phosphate buffer (pH 5.0), which was delivered initially in the ratio of 15:85 (v/v) for 1 min, then changed to 30:70 (v/v) for next 14 min, and finally equilibrated back to 15:85 (v/v) from 15 to 20 min. Other HPLC parameters were: flow rate, 1 ml/min; detection wavelength, 225 nm; and injection volume, 5 microl. The method was validated for linearity, precision, accuracy, specificity and selectivity. It was also compared with the assay procedures given in British Pharmacopoeia for individual drugs. Similar results were obtained, indicating that the proposed single method allowed selective analysis of both ampicillin and cloxacillin, in the presence of their degradation products formed under a variety of stress conditions. The developed procedure was also applicable to the determination of instability of the drugs in commercial products.

A spectrophotometric method is described for the assay of ampicillin in the presence of cloxacillin in pharmaceutical preparations. It involves the reaction of hydrolysed ampicillin with formaldehyde in an acidic phosphate buffer (pH 2.5) and measurement of the absorbance of the product at 373 nm after dilution with 2 M sulphuric acid. The method is selective for ampicillin in the presence of cloxacillin. The absorbance had a linear relationship with concentration for the range studied (5-35 micrograms ml-1). By this method the ampicillin content of combined preparations of ampicillin and cloxacillin has been successfully determined in capsules, injections and a syrup.

A rapid, specific and sensitive high pressure liquid chromatographic (HPLC) assay for the simultaneous determination of ampicillin and cloxacillin in serum and urine is developed. Ampicillin, cloxacillin and cephalexin (internal standard) were eluted from a 6.5 mu Synchropack RPP reversed phase column at ambient temperature using a mobile phase comprised of methanol:water (3/7v/v) and containing 0.011 M sodium-n-octane sulphonate, 0.005 M NaH2PO4 and 1.3% v/v of 0.5 M HCl (pH 2.7). The analysis time required no longer than 11 min. Equations are presented for the linear relationships between the peak height ratios of ampicillin/cephalexin and cloxacillin/cephalexin over the range 10-80 micrograms/ml (ampicillin) and 5-25 micrograms/ml (cloxacillin), respectively. The sensitivity limits for ampicillin and cloxacillin in serum and urine were 5 micrograms/ml and 1 microgram/ml, respectively. Quality criteria such as accuracy, precision and specificity were studied extensively. We investigated the applicability of the HPLC assay for the developed simultaneous determination of the cumulative amounts of ampicillin and cloxacillin, excreted unchanged in urine after an oral dose containing 500 mg ampicillin and 500 mg cloxacillin to a human volunteer.

A fast cylinder plate microbiological method was developed for the quantitative determination of penicillin G, ampicillin, and cloxacillin in milk. Agar plates seeded with stable spores of Bacillus stearothermophilus var. calidolactis were used and incubated at 64 degrees C for 4 1/2 hr. Standard curves were obtained for the following ranges of concentration of antibiotics: 0.004-0.064 IU penicillin G/mL, 0.0025-0.04 microgram ampicillin/mL, and 0.03-0.48 microgram cloxacillin/mL. The method is suitable for detecting penicillin residues in milk and for quantitative milk-out studies of the above antibiotics used in treatment of bovine mastitis.

1. A study has been made of serum, mixed and parotid salivary levels attained in normal volunteers following oral dosage of 500 mg phenoxymethylpenicillin tablets, 500 mg crushed phenoxymethylpenicillin tablets in capsules, 500 mg ampicillin, 500 mg cloxacillin and 500 mg cephalexin.2. High mixed saliva levels were obtained with phenoxymethylpenicillin tablets and it is considered that these were due to rapid intra-oral dissolution of surface powder from friable tablets. No saliva levels were detected when tablets from the same batch were put into capsules.3. Low or no saliva levels were achieved with ampicillin, cloxacillin and cephalexin.4. The mode of action of antibiotics in oral infections is discussed.

A simplified method of assaying mixtures of ampicillin and cloxacillin is presented. The method consists of cylinder-plate assays of appropriately diluted samples in three assay systems in which: (i) cloxacillin is measured, utilizing agar seeded with a penicillinase-producing Staphylococcus aureus; (ii) ampicillin is measured after the greatest dilution practicable, by use of agar seeded with Sarcina lutea; and (iii) the proportion of activity found in the second assay that remains after treatment with staphylococcal penicillinase is determined on agar seeded with S. lutea. The error was 4% or less when each system was run in quadruplicate, except when there was 10 or more times as much cloxacillin as ampicillin, in which case the greatest error was 12%. Mixtures of methicillin with benzylpenicillin or with ampicillin can also be quantitated by this method.