The effect of verapamil on the pharmacokinetics of paclitaxel in rats

Choi, Jun‐Shik; Li, Xiuguo

doi:10.1016/j.ejps.2004.10.002

Cited by 47 publications

(31 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Plasma concentration and oral bioavailability are prominently increased by pretreatment with verapamil, indicating that inhibition of P-gp markedly boosts the extent of PTX absorption via the portal blood. These results are consistent with the results reported by Choi & Li (2005), Woo et al (2003) and Park et al (2012). In these studies, P-gp inhibitors such as verapamil, verapamil analog KR30031 and silymarin were used to increase the bioavailability of PTX by inhibiting either the P-gp efflux pump or cytochrome P-450 (CYP3A).…”

Section: Discussionsupporting

confidence: 82%

“…The bioavailability and the pharmacokinetic parameters of PTX after coadministration with FA/MG and (or) pretreatment with verapamil are shown in Table 1. The absolute bioavailability (AB%) of the drug was only 3.01% when the PTX solution was administered; this poor exposure of PTX from the PTX solution in rats was similar to the values reported in the literature (Choi & Li, 2005;Lee & Choi, 2010). Mean AUC 0-8 h and C max of PTX following introduodenal administration of PTX in combination with FA/MG solution were similar to the corresponding values obtained for the controls.…”

Section: Pharmacokinetics Of Ptxsupporting

confidence: 72%

“…Previous studies have indicated that 54% of a PTX oral dose is extruded to the gut lumen by P-gp, when taken orally (Woo et al, 2003). The oral bioavailability is greatly improved by inhibiting the function and/or expression of P-gp by administering verapamil or verapamil analogs in both the patients and animals (Woo et al, 2003;Choi & Li, 2005). Although much effort has been put into the identification of the effects of P-gp efflux process on the portal and systemic blood levels of PTX, much less is known about the relative role of P-gp efflux processes in the lymph uptake of PTX.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Effects of lipid vehicle and P-glycoprotein inhibition on the mesenteric lymphatic transport of paclitaxel in unconscious, lymph duct-cannulated rats

Cai

Deng

et al. 2014

Drug Delivery

View full text Add to dashboard Cite

The present study examined the effects of lipid vehicle and intestinally based efflux processes on intestinal lymphatic transport of paclitaxel (PTX) in the mesenteric lymph duct-cannulated anesthetized rat model. PTX solution alone, PTX solution pretreated with the P-glycoprotein (P-gp) inhibitor verapamil and/or PTX and a 2:1 (w/w) mixture of linoleic acid:glycerol monooleate were administered intraduodenally to anesthetized rats. Coadministration of a mixture of linoleic acid-monoolein significantly increased the extent of intestinal lymphatic transport of PTX, but it had little impact on the absolute oral bioavailability of PTX. In contrast, pretreatment with verapamil increased both the extent of lymphatic transport (3.5-fold) and absolute oral bioavailability (1.8-fold). Further increase in the lymphatic transport (6.5-fold) and absolute oral bioavailability (1.8-fold) was achieved by the combination of pretreatment with verapamil and coadministration with the linoleic acid-monoolein mixture. These data indicate that the application of lipid vehicle holds promise for selectively targeted lymphatic delivery of PTX. P-gp inhibition can result in both increased intestinal lymphatic levels and absolute oral bioavailability of PTX.

show abstract

Section: Discussionsupporting

confidence: 82%

Section: Pharmacokinetics Of Ptxsupporting

confidence: 72%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Effects of lipid vehicle and P-glycoprotein inhibition on the mesenteric lymphatic transport of paclitaxel in unconscious, lymph duct-cannulated rats

Cai

Deng

et al. 2014

Drug Delivery

View full text Add to dashboard Cite

show abstract

“…The ability of this drug in enhancing the tissue concentrations and effectiveness of other drug molecules via P-gp inhibition has been widely studied (30)(31)(32). In present study verapamil was used as a P-gp inhibitor regarding to the selectivity of the inhibitory action of the drug on P-gp compared to the cytochrome P450 isoenzyme 2D6, the main enzyme responsible for tramadol metabolism.…”

Section: Resultsmentioning

confidence: 99%

Lack of Evidence for Involvement of P-Glycoprotein in Brain Uptake of the Centrally Acting Analgesic, Tramadol in the Rat

et al. 2012

View full text Add to dashboard Cite

-Purpose. Tramadol Hydrochloride is a widely-used centrally acting analgesic drug, which has some features of being a P-gp substrate. The present study evaluates the functional involvement of Pgp in CNS distribution of tramadol. Methods. The possibe involvement of P-glycoprotein in brain distribution of tramadol was evaluated using a pharmacokinetic approach in two groups of Pgp-inhibited and control rats. Six male Sprague-Dawley rats were used in each group to collect plasma and brain at 1, 5, 10, and 30 min following two tramadol doses of 1 and 10 mg/kg. Results. The brain uptake clearances of tramadol in Pgp-inhibited and control rats were 2.47±0.56 and 2.34±0.56 ml min , respectively, for 10 mg/kg dose. The brain-to-plasma concentration ratio (Kp,app) of more than 1 in all the time points following both the high and low dose cases (sometimes more than 3) indicated the brain accumulation of the drug. Linear correlation was found between tramadol dose and both corresponding plasma and brain concentrations, but the presence of a dose-dependency was not confirmed by the data obtained for brain-to-plasma concentration ratio. Conclusion. Considering the results of the previous studies and the present research, it seems that the brain accumulation of tramadol is not affected by P-gp inhibition which implies that there may be some other transport mechanisms involved in BBB transport of tramadol.

show abstract

“…Paclitaxel, however, is known to be absorbed poorly in the gastrointestinal tract when administered orally Bardelmeijer et al, 2004;Choi & Li, 2005;Bardelmeijer et al, 2000). The reasons for poor absorption were identified to be drug metabolism by cytochrome P450 (CYP) and the existence of the efflux system, such as Pglycoproteins in intestinal epithelial cells and liver (Schellens et al, 2000).…”

Section: Introductionmentioning

confidence: 99%

Development, Optimization and Absorption Mechanism of DHP107, Oral Paclitaxel Formulation for Single-Agent Anticancer Therapy

Lee¹,

Hong²,

Jang³

et al. 2012

New Advances in the Basic and Clinical Gastroenterology

View full text Add to dashboard Cite

The effect of verapamil on the pharmacokinetics of paclitaxel in rats

Cited by 47 publications

References 22 publications

Effects of lipid vehicle and P-glycoprotein inhibition on the mesenteric lymphatic transport of paclitaxel in unconscious, lymph duct-cannulated rats

Effects of lipid vehicle and P-glycoprotein inhibition on the mesenteric lymphatic transport of paclitaxel in unconscious, lymph duct-cannulated rats

Lack of Evidence for Involvement of P-Glycoprotein in Brain Uptake of the Centrally Acting Analgesic, Tramadol in the Rat

Development, Optimization and Absorption Mechanism of DHP107, Oral Paclitaxel Formulation for Single-Agent Anticancer Therapy

Contact Info

Product

Resources

About