The effect of staggered administration of zinc sulfate on the pharmacokinetics of oral cephalexin.
OBJECTIVE
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 500mg alone, concomitantly with zinc 250mg, 3h after zinc 250mg or 3h before zinc 250mg.


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 3h 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 3h 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 3h after a cephalexin dose.
Department of Pharmacy, Xijing Hospital of the Fourth Military Medical University, Xi'an, China.
Yi
Y
Ding
Yan-Yan
YY
Jia
Fan
F
Li
Wen-Xing
WX
Liu
Cheng-Tao
CT
Lu
Yan-Rong
YR
Zhu
Jing
J
Yang
Li-Kun
LK
Ding
Lin
L
Yang
Ai-Dong
AD
Wen
D000284:Administration, Oral; D000328:Adult; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001682:Biological Availability; D002506:Cephalexin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004347:Drug Interactions; D006801:Humans; D008297:Male; D019287:Zinc Sulfate / Q000008:administration & dosage / Q000494:pharmacology*
D000900:Anti-Bacterial Agents; D019287:Zinc Sulfate; D002506:Cephalexin