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  • Title: Benzylpenicillin inhibits the renal excretion of acyclovir by OAT1 and OAT3.
    Author: Ye J, Liu Q, Wang C, Meng Q, Sun H, Peng J, Ma X, Liu K.
    Journal: Pharmacol Rep; 2013; 65(2):505-12. PubMed ID: 23744435.
    Abstract:
    BACKGROUND: Acyclovir is acyclic guanosine derivative. Benzylpenicillin (PCG) is a β-lactam antibiotic. The purpose of this study was to investigate the pharmacokinetic drug-drug interaction (DDI) between PCG and acyclovir. METHOD: When acyclovir and PCG were co-administered, plasma concentration of acyclovir, urinary excretion of acyclovir in vivo, uptake of acyclovir in kidney slices and uptake of acyclovir in human (h) OAT1/hOAT3- HEK293 cells were determined to examine the effect of PCG on urinary excretion of acyclovir. RESULTS: The plasma concentration of acyclovir was increased markedly and accumulative renal excretion and renal clearance of acyclovir were decreased significantly after intravenous administration of acyclovir in combination with PCG. PCG could decrease the uptake of acyclovir in kidney slices and in hOAT1-/hOAT3-human embryonic kidney (HEK293) cells. CONCLUSIONS: It indicates that acyclovir is a substrate for OAT1 and OAT3. PCG inhibits the renal excretion of acyclovir by inhibiting renal transporters OAT1 and OAT3 in vivo and in vitro. These results suggest important information for DDI between PCG and acyclovir in kidney.
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