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

Figures & data

Table 1 Treatment-emergent adverse events

	VPA alone (n=16)		AMC + VPA (n=16)
	Number of events	Number (%) of subjects	Number of events	Number (%) of subjects
Diarrhea	1	1 (6.25)	3	3 (18.75)
Dyspepsia	0	0 (0.00)	1	1 (6.25)
Asthenia	0	0 (0.00)	1	1 (6.25)
Increased blood bilirubin	0	0 (0.00)	1	1 (6.25)
Increased blood creatine phosphokinase	0	0 (0.00)	2	2 (12.50)
Decreased neutrophil count	1	1 (6.25)	1	1 (6.25)
Headache	0	0 (0.00)	1	1 (6.25)
Hypoesthesia	0	0 (0.00)	1	1 (6.25)
Presyncope	0	0 (0.00)	1	1 (6.25)
Somnolence	0	0 (0.00)	1	1 (6.25)
Nocturia	0	0 (0.00)	1	1 (6.25)
Total	2	2 (12.50)	14	9 (56.25)

Abbreviations: VPA, valproic acid; AMC, amoxicillin/clavulanic acid.

Table 2 Pharmacokinetic parameters and statistical comparisons of VPA with and without AMC in healthy subjects

	Treatment		Statistical comparison
			GMR
	VPA alone (n=15)	AMC + VPA (n=15)	Point estimate (90% CI)
Cmax (mg/L)	53.0	52.1	0.9834 (0.9161, 1.0556)
AUClast (h·mg/L)	889.6	851.0	0.9566 (0.8589, 1.0654)
AUC4–12 (h·mg/L)	315.6	301.2	0.9544 (0.8860, 1.0282)
tmax (h)	4.00 (2.00, 5.00)	3.33 (2.00, 5.00)	–
t1/2 (h)	15.8 (3.0)	15.6 (3.4)	–

Notes: All values, except for t_max and t_1/2, are presented as the geometric mean. Values for t_max and t_1/2 are presented as the median (minimum, maximum) and the arithmetic mean (standard deviation), respectively.

Abbreviations: VPA, valproic acid; AMC, amoxicillin/clavulanic acid; GMR, geometric mean ratio; CI, confidence interval; C_max, maximum concentration; AUC_last, area under the plasma concentration–time curve from time 0 to the last quantifiable concentration; AUC_4–12, partial AUC from 4 hours to 12 hours; t_max, time to C_max; h, hours; t_1/2, elimination half-life.

Figure 1 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.