Limits...
Effects of amoxicillin/clavulanic acid on the pharmacokinetics of valproic acid.

Lee SY, Huh W, Jung JA, Yoo HM, Ko JW, Kim JR - Drug Des Devel Ther (2015)

Bottom Line: This study aimed to evaluate the effects of AMC on the pharmacokinetics of VPA.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul, Republic of Korea.

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.

No MeSH data available.


Related in: MedlinePlus

Mean plasma VPA concentration–time profiles with and without AMC in healthy subjects.Note: Error bars represent standard deviation.Abbreviations: h, hour; VPA, valproic acid; AMC, amoxicillin/clavulanic acid.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4539086&req=5

f1-dddt-9-4559: Mean plasma VPA concentration–time profiles with and without AMC in healthy subjects.Note: Error bars represent standard deviation.Abbreviations: h, hour; VPA, valproic acid; AMC, amoxicillin/clavulanic acid.

Mentions: Mean plasma VPA concentration–time profiles are shown in Figure 1. After reaching Cmax, plasma VPA concentrations appeared to decline in a monophasic manner. Pharmacokinetic parameters and statistical comparisons of VPA are shown in Table 2. When coadministered with AMC, the Cmax and AUClast of VPA decreased by 1.5% and 4.4%, respectively. There was no difference in the partial AUC4–12 between treatments. The median tmax value was comparable between treatments. The mean t1/2 value was approximately 16 hours in both treatments. The GMRs with 90% CIs for the AUClast, AUC4–12, and Cmax fell entirely within a range of 0.80–1.25, which indicates no significant interaction with AMC.


Effects of amoxicillin/clavulanic acid on the pharmacokinetics of valproic acid.

Lee SY, Huh W, Jung JA, Yoo HM, Ko JW, Kim JR - Drug Des Devel Ther (2015)

Mean plasma VPA concentration–time profiles with and without AMC in healthy subjects.Note: Error bars represent standard deviation.Abbreviations: h, hour; VPA, valproic acid; AMC, amoxicillin/clavulanic acid.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4539086&req=5

f1-dddt-9-4559: Mean plasma VPA concentration–time profiles with and without AMC in healthy subjects.Note: Error bars represent standard deviation.Abbreviations: h, hour; VPA, valproic acid; AMC, amoxicillin/clavulanic acid.
Mentions: Mean plasma VPA concentration–time profiles are shown in Figure 1. After reaching Cmax, plasma VPA concentrations appeared to decline in a monophasic manner. Pharmacokinetic parameters and statistical comparisons of VPA are shown in Table 2. When coadministered with AMC, the Cmax and AUClast of VPA decreased by 1.5% and 4.4%, respectively. There was no difference in the partial AUC4–12 between treatments. The median tmax value was comparable between treatments. The mean t1/2 value was approximately 16 hours in both treatments. The GMRs with 90% CIs for the AUClast, AUC4–12, and Cmax fell entirely within a range of 0.80–1.25, which indicates no significant interaction with AMC.

Bottom Line: This study aimed to evaluate the effects of AMC on the pharmacokinetics of VPA.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul, Republic of Korea.

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.

No MeSH data available.


Related in: MedlinePlus