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The effect of staggered administration of zinc sulfate on the pharmacokinetics of oral cephalexin
Author(s) -
Ding Yi,
Jia YanYan,
Li Fan,
Liu WenXing,
Lu ChengTao,
Zhu YanRong,
Yang Jing,
Ding LiKun,
Yang Lin,
Wen AiDong
Publication year - 2012
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1111/j.1365-2125.2011.04098.x
Subject(s) - bioavailability , pharmacokinetics , zinc , dosing , pharmacology , medicine , antibiotics , minimum inhibitory concentration , oral administration , drug , chemistry , biochemistry , organic chemistry
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 ( C max ), area under the plasma concentration–time curve from zero to infinity (AUC 0–∞ ) 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 C max , AUC 0–∞ 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.