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

Abstract

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 (C max) and longer time to reach C max (T max) were observed in OY pretreated rats without changes in the area under the curve (AUC) and the fraction excreted into urine (F urine). The absorption rate (K a) 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.

Alterations in Pharmacokinetics of Gemcitabine and Erlotinib by Concurrent Administration of Hyangsayukgunja-Tang, a Gastroprotective Herbal Medicine

“…To further evaluate the HYT effect on pharmacokinetics of erlotinib and its metabolites, we developed a population pharmacokinetic model. Population pharmacokinetic modeling has been suggested to be a useful tool for evaluation of drug-drug or herb-drug interactions [ 30 ]. The present pharmacokinetic model ( Figure 3 ) was designed to describe the absorption, disposition, and elimination of erlotinib, OSI-420, and OSI-413.…”

“…Nevertheless, potential interactions between anticancer agents and herbal remedies are not well known. Concurrent use of the herbal remedies with conventional western drugs may mimic, augment, or oppose the pharmacokinetics or pharmacodynamics, leading to either increase or decrease of their effects [ 30 ], which requires attention.…”

Effect of Sipjeondaebo-Tang on the Pharmacokinetics of S-1, an Anticancer Agent, in Rats Evaluated by Population Pharmacokinetic Modeling

“…Herbal medicines may provide useful options to relieve chemotherapy-related toxicities and improve the conditions of patients after surgery or illness. The concurrent use of herbs and pharmaceutical drugs may mimic, augment, or oppose the pharmacokinetics or pharmacodynamics, thereby increasing or decreasing the pharmacological or toxicological effects of either constituent [ 11 ]. Although drug interactions of S-1 with certain conventional western drugs have been reported [ 12 , 13 ], there has been no information on drug-herb interaction between S-1 and herbal medicines.…”

Validated Method for the Quantification of Baclofen in Human Plasma Using Solid-Phase Extraction and Liquid Chromatography–Tandem Mass Spectrometry

“…Most published methods utilized structurally similar compounds to baclofen as an internal standard (9,10,17,18,21,22), rather than using the deuterated analog (baclofen-d 4 ). It is important to use the deuterated analog when analysis is performed by LC-MS-MS as it is the only way to truly compensate for potential matrix enhancement or suppression.…”

“…Many LC-MS-MS methods only monitor one product ion (17,18,21,22), while others monitor two (23) or three (19) product ions for both quantification and confirmation. In cases where only one product ion is monitored, there is a potential for reporting a false-positive result.…”