Naftopidil, A Novel Antihypertensive Drug

Enantiospecific determination of naftopidil by RRLC–MS/MS reveals stereoselective pharmacokinetics and tissue distributions in rats

“…Preliminary tests on the brain showed that R(+)-and S(−)-NAF concentrations in most samples were below the lowest LOQ obtained. These results are consistent with previous studies on racemic NAF [10,19] that reported that only miniscule amounts of NAF enantiomers were distributed in the rat brain. Therefore, the distributions of R(+)-and S(−)-NAF in the brain were not determined in this work.…”

“…According to previous studies on racemic NAF, pronounced firstpass metabolism occurs in rats and human [10]. In addition, the stereochemistry of a compound is widely known to exhibit minimal influence on passive processes.…”

“…Data further suggest that NAF can potentially be used for LUTS/BPH and PCa treatment and prevention. However, because of its low bioavailability (9% in rats and 18% in human), the clinical medication dose of racemic NAF is as high as 25-75 mg/kg, which is more than that of other BPH therapeutic drugs (e.g., 0.2 mg/day tamsulosin, 1-5 mg/day terazosin, and 5 mg finasteride) [10]. For this reason, we sought to investigate the pharmacokinetics of NAF in this study.…”

Determination of naftopidil enantiomers in rat plasma using chiral solid phases and pre-column derivatization high-performance liquid chromatography

“…Using Chiralcel OD, Aboul-Enein et al (1995) separated chemical pure naftopidil but without validation, while Sun et al (2009) achieved resolution of naftopidil enantiomers using Chiralpak AD-H but with high quantitation limits (780 ng/mL and 840 ng/mL). Since absolute bioavailability of racemic naftopidil has been shown to be very low (9%) [15], increasing the quantitation limits is the most critical requirement for bioanalysis of naftopidil enantiomers. Furthermore, reversed phase mode is more suitable compared to normal phase mode for complicated bioanalysis for two major reasons.…”

Identification of human cytochrome P450 isozymes involved in the metabolism of naftopidil enantiomers in vitro

“…A previous study showed that 80–95% of dose racemic NAF was rapidly absorbed but had low bioavailability in humans, suggesting the presence of a marked first‐pass metabolism [10]. However, not only limited studies about the metabolism of NAF in vitro / in vivo were addressed but also the disposition of individual NAF enantiomer was not clarified.…”