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WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • Zinc supplementation is an important intervention against mortality from infectious disease. • Many patients using zinc supplementation will also be prescribed antimicrobials at some time. • Recently, an inhibitory effect of zinc on the absorption of β-lactam antibiotics has been demonstrated in animal studies, but there has been no clinical assessment of this drug-nutrient interaction. WHAT THIS STUDY ADDS • Zinc sulfate dosing significantly impaired the bioavailability and decreased T > MIC of cephalexin in healthy volunteers, which might lead to a clinical failure. • The dosing recommendation is that zinc sulfate can be safely administered 3 h after a cephalexin dose. AIMS To investigate the effect of zinc sulfate on pharmacokinetics of cephalexin when administered concurrently or at strategically spaced dosing times designed to avoid the potential interaction in healthy volunteers. METHODS In this study, all subjects ( n= 12) were randomized to receive the following four treatments, separated by a wash-out period of 7 days: cephalexin 500 mg alone, concomitantly with zinc 250 mg, 3 h after zinc 250 mg or 3 h before zinc 250 mg. RESULTS All subjects completed the study safely. Zinc supplements administered concurrently with cephalexin significantly decreased the peak serum concentration ( Cmax), area under the plasma concentration-time curve from zero to infinity (AUC0-∞) and the time for which the plasma concentration of the drug remained above the minimal inhibitory concentration of the pathogenic organism ( T > MIC) of cephalexin [mean percentage decrease (95% confidence intervals) of 31.05% (22.09-40.01%), 27.40% (18.33-36.47%) and 22.33% (12.51-32.16%), respectively; P < 0.05] compared with administration of cephalexin alone. Also, administration of zinc 3 h before cephalexin decreased the Cmax, AUC0-∞ and T > MIC of the drug compared with administration of cephalexin alone [mean percentage decrease (95% confidence intervals) of 11.48% (3.40-19.55%), 18.12% (9.63-26.60%) and 23.75% (14.30-33.20%), respectively; P < 0.05]. In contrast, the pharmacokinetics of cephalexin was not notably altered by administration of zinc 3 h after cephalexin dosing ( P > 0.05). CONCLUSIONS The significant interaction between zinc and cephalexin might affect the clinical outcome of cephalexin therapy. The dosing recommendation is that zinc sulfate can be safely administered 3 h after a cephalexin dose. [ABSTRACT FROM AUTHOR]

Abstract: A sensitive method using liquid chromatography with tandem mass spectrometric detection (LC–MS/MS) was developed and validated for the analysis of antihistamine drug azatadine in human plasma. Loratadine was used as internal standard (IS). Analytes were extracted from human plasma by liquid/liquid extraction using ethyl acetate. The organic phase was reduced to dryness under a stream of nitrogen at 30°C and the residue was reconstituted with the mobile phase. 5μL of the resulting solution was injected onto the LC–MS/MS system. A 4.6mm×150mm, I.D. 5μm, Agilent TC-C18 column was used to perform the chromatographic analysis. The mobile phase consisted of ammonium formate buffer 0.010M (adjusted to pH 4.3 with 1M formic acid)/acetonitrile (20:80, v/v) The chromatographic run time was 5min per injection and flow rate was 0.6mL/min. The retention time was 2.4 and 4.4min for azatadine and IS, respectively. The tandem mass spectrometric detection mode was achieved with electrospray ionization (ESI) iron source and the multiple reaction monitoring (MRM) (291.3→248.2 m/z for azatadine, 383.3→337.3 m/z for IS) was operated in positive ion modes. The low limit of quantitation (LLOQ) was 0.05ng/mL. The intra-day and inter-day precision of the quality control (QC) samples was 8.93–11.57% relative standard deviation (RSD). The inter-day accuracy of the QC samples was 96.83–105.07% of the nominal values. [Copyright &y& Elsevier]

Abstract: Ropinirole is a nonergoline dopamine D2-receptor agonist and has been proven to be effective in both monotherapy and combination therapy for idiopathic Parkinson''s disease. The purpose of the present study was to examine the effect of Madopar on the pharmacokinetics of ropinirole in healthy Chinese volunteers by using liquid chromatography tandem mass spectrometry (HPLC/MS/MS). A single dose of 1mg ropinirole was given orally after administration of the placebo or Madopar (containing 200mg levodopa and 50mg benserazide) to six healthy males and six healthy females in a cross-over randomized study with a minimum washout period of 8 days. Pharmacokinetic parameters were calculated for both treatments. Coadministration of ropinirole and Madopar did not result in a notable change in rate or extent of availability of ropinirole, as shown by the ratios (90% confidence intervals) of 1.045 (0.900, 1.222) for C max (maximum plasma concentration) and 1.167 (1.086, 1.262) for AUC0–inf (the area under the concentration–time curve). Likewise, no significant difference in any of the other pharmacokinetic parameters [T max (the time needed to reach the C max), MRT (mean residence time), volume of distribution (V/F), and clearance (CL/F)] was observed between the treatment groups. No clinically relevant adverse effects were detected under either conditions and there are no pharmacokinetic grounds for adjusting the dose of ropinirole when given in combination with Madopar in Chinese patients. [Copyright &y& Elsevier]

Ethnopharmacological relevance: Safflower is a popular Traditional Chinese Medicine (TCM) to invigorate the blood and dispel ‘blood stasis’, which arises from poor blood circulation. The differences of pharmacokinetic properties between normal and blood stasis syndrome rats were seldom reported. Aim of the study: The present study was conducted to evaluate the pharmacokinetics of hydroxysafflower yellow A (HSYA) following oral administration of hydroxysafflower yellow A and safflower extract with approximately the same dose of HSYA 100mg/kg in both normal and acute blood stasis rats. Materials and methods: The animals were orally administered with HYSA monomer and safflower extract. The blood samples were collected according to the time schedule. The concentrations of HSYA in rat plasma were determined by HPLC. Various pharmacokinetic parameters were estimated from the plasma concentration versus time data using non-compartmental methods. Results: It was found that AUC0–t , C max, Vd and CL of HSYA in both HSYA monomer and safflower extract in acute blood stasis rats were with significant difference (P <0.05) comparing with that in normal rats. Conclusions: The results indicated that HSYA was with high uptake and eliminated slowly in the animals with blood stasis syndrome, suggesting that the rate and extent of drug metabolism was altered in acute blood stasis animals. [Copyright &y& Elsevier]