Pharmacokinetic Alteration of Baclofen by Multiple Oral Administration of Herbal Medicines in Rats

Abstract EN

The potential pharmacokinetic (PK) interaction of conventional western drug, baclofen, and oriental medications Oyaksungisan (OY) and Achyranthes bidentata radix (AB) extract for the treatment of spasticity has been evaluated.

Rats were pretreated with distilled water (DW), OY, or AB extract by oral administration every day for 7 days.

After 10 min of the final dose of DW or each herbal medication, baclofen (1 mg/kg) was given by oral administration and plasma concentrations of baclofen were determined by LC/MS/MS.

The plasma baclofen concentration-time profiles were then analyzed by noncompartmental analysis and a population PK model was developed.

Baclofen was rapidly absorbed, showed biexponential decline with elimination half-life of 3.42–4.10 hr, and mostly excreted into urine.

The PK of baclofen was not affected by AB extract pretreatment.

However, significantly lower maximum plasma concentration (Cmax) and longer time to reach Cmax (Tmax) were observed in OY pretreated rats without changes in the area under the curve (AUC) and the fraction excreted into urine (Furine).

The absorption rate (Ka) of baclofen was significantly decreased in OY pretreated rats.

These data suggested that repeated doses of OY might delay the absorption of baclofen without changes in extent of absorption, which needs further evaluation for clinical significance.