Acute and Chronic Administrations of Rheum palmatum Reduced the Bioavailability of Phenytoin in Rats: A New Herb-Drug Interaction

Table 1

Pharmacokinetic parameters of PHT, PHT-G, HPPH, and HPPH-G in six rats receiving oral PHT (200 mg/kg) alone and coadministration with single dose and seven doses of RP decoction (2 g/kg).

Parameters	Treatments
	PHT alone	PHT + RP; (2 g/kg)	PHT + RP; (7th dose of 2 g/kg)
PHT
𝐶max	15.7 ± 0.7^a	7.5 ± 0.6^b	7.3 ± 0.6^b
		(−51.0 ± 5.1%)	(−53.1 ± 3.7%)
AUC0-720	4261.3 ± 146.8^a	2650.0 ± 211.1^b	2024.9 ± 209.0^b
		(−36.9 ± 6.6%)	(−51.9 ± 5.3%)
𝐾10	0.0039 ± 0.0002^a	0.0028 ± 0.0003^b	0.0025 ± 0.0002^b
		(−27.9 ± 7.9%)	(−30.4 ± 6.2%)
PHT-G
𝐶max	1.7 ± 0.2^a	0.8 ± 0.1^b	0.5 ± 0.1^b
		(−51.7 ± 4.2%)	(−65.1 ± 10.4%)
AUC0-720	557.2 ± 59.9^a	232.5 ± 37.9^b	172.5 ± 22.1^b
		(−51.7 ± 12.1%)	(−64.8 ± 8.5%)
𝐾10	0.0033 ± 0.0003^a	0.0019 ± 0.0002^b	0.0023 ± 0.0003^b
		(−51.5 ± 4.9%)	(−39.9 ± 7.3%)
HPPH
𝐶max	4.5 ± 0.3^a	2.5 ± 0.1^b	2.3 ± 0.1^b
		(−43.9 ± 4.6%)	(−46.3 ± 6.9%)
AUC0-720	1556.0 ± 81.5^a	1058.3 ± 45.1^b	954.0 ± 49.8^b
		(−30.3 ± 5.7%)	(−37.5 ± 5.0%)
𝐾10	0.0013 ± 0.0002^a	0.0008 ± 0.0003^b	0.0003 ± 0.0001^b
		(−67.9 ± 13.8%)	(−76.6 ± 7.0%)
HPPH-G
𝐶max	14.8 ± 0.7^a	8.4 ± 0.5^b	8.1 ± 0.5^b
		(−42.5 ± 4.0%)	(−44.3 ± 4.2%)
AUC0-720	4482.9 ± 114.7^a	3430.8 ± 208.5^b	3099.9 ± 155.0^b
		(−22.8 ± 6.3%)	(−30.6 ± 3.7%)
𝐾10	0.0039 ± 0.0002^a	0.0018 ± 0.0002^b	0.0016 ± 0.0002^b
		(−53.6 ± 3.9%)	(−59.3 ± 4.7%)

^a, b Significant difference at 𝑃<0.05 denoted by different letters.
𝐶_max (μg/mL): peak serum concentration.
AUC_0-720 (μg·min/mL): areas under the curves from time zero to the last point.
𝐾₁₀: the elimination rate (min⁻¹).
Values are means ± SE.