title: Effects of amoxicillin/clavulanic acid on the pharmacokinetics of valproic acid.
abstract: Valproic acid (VPA) is mainly metabolized via glucuronide, which is hydrolyzed by β-glucuronidase and undergoes enterohepatic circulation. Amoxicillin/clavulanic acid (AMC) administration leads to decreased levels of β-glucuronidase-producing bacteria, suggesting that these antibiotics could interrupt enterohepatic circulation and thereby alter the pharmacokinetics of VPA. This study aimed to evaluate the effects of AMC on the pharmacokinetics of VPA. This was an open-label, two-treatment, one-sequence study in 16 healthy volunteers. Two treatments were evaluated; treatment VPA, in which a single dose of VPA 500 mg was administered, and treatment AMC + VPA, in which multiple doses of AMC 500/125 mg were administered three times daily for 7 days and then a single dose of VPA was administered. Blood samples were collected up to 48 hours. Pharmacokinetic parameters were calculated using noncompartmental methods. Fifteen subjects completed the study. Systemic exposures and peak concentrations of VPA were slightly lower with treatment AMC + VPA than with treatment VPA (AUClast, 851.0 h·mg/L vs 889.6 h·mg/L; C max, 52.1 mg/L vs 53.0 mg/L). There were no significant between-treatment effects on pharmacokinetics (95% confidence interval [CI]) of AUClast and C max (95.7 [85.9-106.5] and 98.3 [91.6-105.6], respectively). Multiple doses of AMC had no significant effects on the pharmacokinetics of VPA; thus, no dose adjustment is necessary.
authors: Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul, Republic of Korea.
authors: Soo-Yun
authors: SY
authors: Lee
authors: Department of Clinical Pharmacology and Therapeutics, Samsung Medical Center, Seoul, Republic of Korea.
authors: Wooseong
authors: W
authors: Huh
authors: Department of Clinical Pharmacology, Inje University, Busan Paik Hospital, Busan, Republic of Korea.
authors: Jin Ah
authors: JA
authors: Jung
authors: Department of Clinical Pharmacology and Therapeutics, Samsung Medical Center, Seoul, Republic of Korea.
authors: Hye Min
authors: HM
authors: Yoo
authors: Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul, Republic of Korea ; Department of Clinical Pharmacology and Therapeutics, Samsung Medical Center, Seoul, Republic of Korea.
authors: Jae-Wook
authors: JW
authors: Ko
authors: Department of Clinical Pharmacology and Therapeutics, Samsung Medical Center, Seoul, Republic of Korea ; Department of Clinical Research and Evaluation, SAIHST, Sungkyunkwan University, Seoul, Republic of Korea.
authors: Jung-Ryul
authors: JR
authors: Kim
mesh_terms: D000328:Adult; D019980:Amoxicillin-Potassium Clavulanate Combination / Q000008:administration & dosage* / Q000009:adverse effects; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000009:adverse effects; D000927:Anticonvulsants / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001711:Biotransformation; D004334:Drug Administration Schedule; D004347:Drug Interactions; D004764:Enterohepatic Circulation; D006207:Half-Life; D064368:Healthy Volunteers; D006801:Humans; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D008954:Models, Biological; D056910:Republic of Korea; D014635:Valproic Acid / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives / Q000097:blood / Q000493:pharmacokinetics*; D055815:Young Adult
chemical_list: D000900:Anti-Bacterial Agents; D000927:Anticonvulsants; C041285:valproic acid glucuronide; D014635:Valproic Acid; D019980:Amoxicillin-Potassium Clavulanate Combination
keywords: drug-drug interaction; enterohepatic circulation; pharmacokinetics