title: Benzylpenicillin inhibits the renal excretion of acyclovir by OAT1 and OAT3.
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.
  
  
  METHODS
  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.
authors.affiliation: Department of Clinical Pharmacology, College of Pharmacy, Dalian Medical University, 9 West Section, Lvshun South Road, Lvshunkou District, Dalian 116044, China.
authors.forename: Jianghao
authors.initials: J
authors.lastname: Ye
authors.forename: Qi
authors.initials: Q
authors.lastname: Liu
authors.forename: Changyuan
authors.initials: C
authors.lastname: Wang
authors.forename: Qiang
authors.initials: Q
authors.lastname: Meng
authors.forename: Huijun
authors.initials: H
authors.lastname: Sun
authors.forename: Jinyong
authors.initials: J
authors.lastname: Peng
authors.forename: Xiaochi
authors.initials: X
authors.lastname: Ma
authors.forename: Kexin
authors.initials: K
authors.lastname: Liu
mesh_terms: D000212:Acyclovir / Q000493:pharmacokinetics*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D000998:Antiviral Agents / Q000494:pharmacology; D004347:Drug Interactions; D057809:HEK293 Cells; D006801:Humans; D007668:Kidney / Q000378:metabolism; D008297:Male; D027362:Organic Anion Transport Protein 1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D029362:Organic Anion Transporters, Sodium-Independent / Q000037:antagonists & inhibitors* / Q000378:metabolism; D010400:Penicillin G / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000900:Anti-Bacterial Agents; D000998:Antiviral Agents; D027362:Organic Anion Transport Protein 1; D029362:Organic Anion Transporters, Sodium-Independent; C114338:organic anion transport protein 3; D010400:Penicillin G; D000212:Acyclovir