In Vitro Effects of Plasma Collected From Rats Administered Naftopidil on Whole Urinary Bladder Preparation Isolated From Rats / 대한배뇨장애요실금학회지

PURPOSE: Alpha-1-adrenoceptor blockers (e.g., naftopidil) are prescribed for the treatment of male lower urinary tract symptoms. Although the mechanism of action of naftopidil has been studied in various organs, that in the urinary bladder remains unknown. To clarify the direct effects of naftopidil on this organ, activities were assessed in the isolated rat whole urinary bladder.METHODS: A total of 30 female rats were used. In Experiment 1, bladder activity was measured during a cumulative administration of 2.5–75μM naftopidil (n=7). In Experiment 2, rats were divided into 2 groups: control (n=10) and naftopidil (5 mg/animal/day, oral gavage, once-daily for 2 weeks) (n=13). After the treatment period, plasma was obtained from each rat. The urinary bladders were harvested from the control rats. Isovolumetric rhythmic bladder contractions were induced at above the threshold volume, and intravesical pressure was recorded. Control plasma was added to the organ bath; after subsequent wash-out, plasma collected from rats administered naftopidil was added. In Experiment 3, the plasma levels of monoamines and amino acids were quantified using the individual plasma prepared in the Experiment 2.RESULTS: Cumulative dosing with naftopidil did not change the interval between spontaneous contractions compared to the interval at baseline. After adding control plasma, the interval was shortened compared to the baseline (P=0.008). The plasma collected from rats administered naftopidil suppressed the shortening of the interval compared to the control plasma (P=0.041). Naftopidil resulted in a decrease in the level of noradrenaline (P=0.009) and an increase in that of glycine (P=0.014).CONCLUSIONS: Although naftopidil did not directly act on the interval between spontaneous contractions of the urinary bladder, the plasma collected from rats administered naftopidil, with changing levels of monoamines and amino acids, may suppressed shortening the interval.

Emotional Stress Facilitates Micturition Reflex: Possible Inhibition by an α₁-Adrenoceptor Blocker in the Conscious and Anesthetized State / 대한배뇨장애요실금학회지

PURPOSE: To test the hypothesis that naftopidil prolongs intercontraction intervals in rats undergoing chronic stress as observed in previous animal models, voiding behavior and bladder function were measured and analyzed. METHODS: Female Sprague-Dawley rats weighing 200–230 g were exposed to repeated variate stress (RVS) for 1 week, chronic variable mild stress for 2 weeks, or simple mild stress for 1 week. Voiding behavior was assessed in metabolic cages. Voiding frequency and urine output were measured, and changes of these values were compared for the different types of stress. Micturition reflex was analyzed using unconscious cystometry. Naftopidil was administered orally at 30 mg/kg/day for 2 weeks. RESULTS: Unexpectedly, no stress-exposed rats exhibited increased micturition frequency compared to the normal nonstressed control. However, intercontraction intervals were shortened with each type of stress in the unconscious condition, especially by RVS (P<0.01). Naftopidil prolonged the shortened intervals. CONCLUSIONS: Although voiding behavior appears approximately normal in rats chronically exposed to emotional stress, internal bladder function can be affected. With anesthesia, micturition intervals were moderately shortened by emotional stress and clearly improved by naftopidil. Therefore, naftopidil appears to act at the spinal level at least.

Characterization on Responsiveness of Excitatory Synaptic Transmissions to α1-Adrenoceptor Blockers in Substantia Gelatinosa Neurons Isolated From Lumbo-Sacral Level in Rat Spinal Cords / 대한배뇨장애요실금학회지

PURPOSE: The aim of this study was to characterize the responsiveness of miniature excitatory postsynaptic currents (mEPSCs) to α1-adrenoceptor blockers in substantia gelatinosa (SG) neurons from the spinal cord to develop an explanation for the efficacy of α1-adrenoceptor blockers in micturition dysfunction. METHODS: Male adult Sprague-Dawley rats were used. Blind whole-cell patch-clamp recordings were performed using SG neurons in spinal cord slices. Naftopidil (100μM), tamsulosin (100μM), or silodosin (30μM), α1-adrenoceptor blockers, was perfused. The frequency of mEPSCs was recorded in an SG neuron to which the 3 blockers were applied sequentially with wash-out periods. Individual frequencies in a pair before naftopidil and tamsulosin perfusion were plotted as baseline, and the correlation between them was confirmed by Spearman correlation coefficient; linear regression was then performed. The same procedure was performed before naftopidil and silodosin perfusion. Frequencies of pairs after naftopidil and tamsulosin perfusion and after naftopidil and silodosin perfusion were similarly analyzed. The ratios of the frequencies after treatment to before were then calculated. RESULTS: After the treatments, Spearman ρ and the slope were decreased to 0.682 from 0.899 at baseline and 0.469 from 1.004 at baseline, respectively, in the tamsulosin group relative to the naftopidil group. In the silodosin group, Spearman ρ and the slope were also decreased to 0.659 from 0.889 at baseline and 0.305 from 0.989 at baseline, respectively, relative to the naftopidil group. Naftopidil significantly increased the ratio of the frequency of mEPSCs compared to tamsulosin and silodosin (P=0.015 and P=0.004, respectively). CONCLUSIONS: There was a difference in responsiveness in the frequency of mEPSCs to α1-adrenoceptor blockers, with the response to naftopidil being the greatest among the α1-adrenoceptor blockers. These data are helpful to understand the action mechanisms of α1-adrenoceptor blockers for male lower urinary tract symptoms in clinical usage.

Effects of High Concentrations of Naftopidil on Dorsal Root-Evoked Excitatory Synaptic Transmissions in Substantia Gelatinosa Neurons In Vitro / 대한배뇨장애요실금학회지

PURPOSE: Naftopidil ((±)-1-[4-(2-methoxyphenyl) piperazinyl]-3-(1-naphthyloxy) propan-2-ol) is prescribed in several Asian countries for lower urinary tract symptoms suggestive of benign prostatic hyperplasia. Previous animal experiments showed that intrathecal injection of naftopidil abolished rhythmic bladder contraction in vivo. Naftopidil facilitated spontaneous inhibitory postsynaptic currents in substantia gelatinosa (SG) neurons in spinal cord slices. These results suggest that naftopidil may suppress the micturition reflex at the spinal cord level. However, the effect of naftopidil on evoked excitatory postsynaptic currents (EPSCs) in SG neurons remains to be elucidated. METHODS: Male Sprague-Dawley rats at 6 to 8 weeks old were used. Whole-cell patch-clamp recordings were made using SG neurons in spinal cord slices isolated from adult rats. Evoked EPSCs were analyzed in Aδ or C fibers. Naftopidil or prazosin, an α1-adrenoceptor blocker, was perfused at 100 μM or 10 μM, respectively. RESULTS: Bath-applied 100 μM naftopidil significantly decreased the peak amplitudes of Aδ and C fiber-evoked EPSCs to 72.0%±7.1% (n=15) and 70.0%±5.5% (n=20), respectively, in a reversible and reproducible manner. Bath application of 10μM prazosin did not inhibit Aδ or C fiber-evoked EPSCs. CONCLUSIONS: The present study suggests that a high concentration of naftopidil reduces the amplitude of evoked EPSCs via a mechanism that apparently does not involve α1-adrenoceptors. Inhibition of evoked EPSCs may also contribute to suppression of the micturition reflex, together with nociceptive stimulation.

Crystal structures, absolute configurations and molecular docking studies of naftopidil enantiomers as-adrenoceptor antagonists

Chiral drug naftopidil (NAF), a specific-adrenoceptor (AR) antagonist for the treatment of benign prostatic hyperplasia, was used in racemic form for several decades. Our recent work declared that NAF enantiomers showed the same antagonistic effects on the-AR, but the binding mechanism of these two stereochemical NAF isomers to thereceptor remained unclear. Herein, we reported the crystallographic structures of optically pure NAF stereoisomers for the first time and unambiguously determined their absolute configurations. The crystal data ofandenantiomers matched satisfactorily the pharmacophore model for-selective antagonists. Based on the constructedhomology model, molecular docking studies shed light on the molecular mechanism of NAF enantiomers binding to-AR. The results indicated that NAF enantiomers exhibited the very similar binding poses and occupied the same binding pocket.

Clinical Efficacy and Safety of Naftopidil Treatment for Patients with Benign Prostatic Hyperplasia and Hypertension: A Prospective, Open-Label Study

PURPOSE: To investigate the efficacy and safety of naftopidil for benign prostatic hyperplasia (BPH) patients, mainly focusing on changes in blood pressure (BP). MATERIALS AND METHODS: Of a total of 118 patients, 90 normotensive (NT) and 28 hypertensive (HT) patients were randomly assigned to be treated with naftopidil 50 mg or 75 mg for 12 weeks, once-daily. Safety and efficacy were assessed by analyzing changes from baseline in systolic/diastolic BP and total International Prostate Symptom Score (IPSS) at 4 and 12 weeks. Adverse events (AEs), obstructive/irritative subscores, quality of life (QoL) score, maximum urinary flow rate (Qmax), and benefit, satisfaction with treatment, and willingness to continue treatment (BSW) questionnaire were also analyzed. RESULTS: Naftopidil treatment decreased mean systolic BP by 18.7 mm Hg for the HT 50 mg group (p86% of all patients agreed to continue their current medications. CONCLUSION: Our results suggest that naftopidil treatment in BPH patients with hypertension allows for optimal management of BP within the normal range.

Effect of naftopidil on levels of MIP-2 and MIP-1αin serum and succus prostaticus in the treatment of prostatitis in elderly / 中国生化药物杂志

Objective To investigate the effect of naftopidil in the treatment of prostatitis in the elderly on MIP-2 and MIP-1αin serum and succus prostaticus.Methods 78 elderly patients with chronic prostatitis were randomly divided into the control group and the observation group, 39 cases in each group.The control group were treated with Diosmin routine treatment, the observation group were treated on the basis of the control group combined with naftopidil tablets in the treatment,2 groups were treated continuous for 8 weeks.MIP-2 and MIP-1αin serum and prostatic fluid before and after treatment were compared, and the maximum urine flow rate and clinical efficacy were compared after the treatment.Results compared with pre-treatment, MIP-2, MIP-1αin serum and prostate fluid in 2 groups after treatment decreased, NIH-CPSI and QOL scores in 2 groups decreased, the maximum urinary flow rate increased (P<0.05);compared with the control group, the levels of MIP-2, MIP-1αin the serum and prostatic fluid, NIH-CPSI and QOL of observation group were lower, and the maximum urine flow rate was higher (P<0.05);Compared with the control group, the total efficiency of the observation group was higher (P<0.05).Conclusion Naftopidil can significantly reduce the elderly patients with chronic non bacterial prostatitis and serum of patients with prostatic fluid MIP-2, MIP-1αlevel and improve pain in urination, dysuria symptoms.

Effects of Combination Treatment of Alpha 1-Adrenergic Receptor Antagonists on Voiding Dysfunction: Study on Target Organs in Overactive Bladder Rats / 대한배뇨장애요실금학회지

PURPOSE: Overactive bladder (OAB) causes urinary urgency, usually accompanied by frequency and nocturia. Alpha 1-adrenergic receptor (α1-AR) antagonists are known to improve lower urinary tract symptoms associated with OAB. The α1-AR antagonists constitute a variety of drugs according to the receptor subtype affinity. This study investigated the efficacy of tamsulosin, naftopidil, and a combination of the two on OAB rats. METHODS: The OAB rat model was induced by an intraperitoneal injection of cyclophosphamide for 14 days. The experimental groups were divided into 5 groups: control group, OAB-induction group, OAB-induction and tamsulosin monotherapy group, OAB-induction and naftopidil monotherapy group, and OAB-induction and tamsulosin-naftopidil combination therapy group. For the drug-treated groups, each drug was administrated for 14 days after the OAB induction. Cystometry for urodynamic evaluation and immunohistochemical stain for c-Fos and nerve growth factor (NGF) expressions in the central micturition centers were performed. RESULTS: Increased contraction pressure and time with enhanced c-Fos and NGF expressions in the central micturition centers were found in the OAB rats. Tamsulosin suppressed contraction pressure and time while inhibiting c-Fos and NGF expressions. Naftopidil showed no significant effect and combination therapy showed less of an effect on contraction pressure and time. Naftopidil and combination therapy exerted no significant effect on the c-Fos and NGF expressions. CONCLUSIONS: Tamsulosin showed the most prominent efficacy for the treatment of OAB compared to the naftopidil and combination. The combination of tamsulosin with naftopidil showed no synergistic effects on OAB; however, further studies of addon therapy might provide opportunities to find a new modality.

Effects of Combination Treatment of Alpha 1-Adrenergic Receptor Antagonists on Voiding Dysfunction: Study on Target Organs in Overactive Bladder Rats / 대한배뇨장애요실금학회지

PURPOSE: Overactive bladder (OAB) causes urinary urgency, usually accompanied by frequency and nocturia. Alpha 1-adrenergic receptor (α1-AR) antagonists are known to improve lower urinary tract symptoms associated with OAB. The α1-AR antagonists constitute a variety of drugs according to the receptor subtype affinity. This study investigated the efficacy of tamsulosin, naftopidil, and a combination of the two on OAB rats. METHODS: The OAB rat model was induced by an intraperitoneal injection of cyclophosphamide for 14 days. The experimental groups were divided into 5 groups: control group, OAB-induction group, OAB-induction and tamsulosin monotherapy group, OAB-induction and naftopidil monotherapy group, and OAB-induction and tamsulosin-naftopidil combination therapy group. For the drug-treated groups, each drug was administrated for 14 days after the OAB induction. Cystometry for urodynamic evaluation and immunohistochemical stain for c-Fos and nerve growth factor (NGF) expressions in the central micturition centers were performed. RESULTS: Increased contraction pressure and time with enhanced c-Fos and NGF expressions in the central micturition centers were found in the OAB rats. Tamsulosin suppressed contraction pressure and time while inhibiting c-Fos and NGF expressions. Naftopidil showed no significant effect and combination therapy showed less of an effect on contraction pressure and time. Naftopidil and combination therapy exerted no significant effect on the c-Fos and NGF expressions. CONCLUSIONS: Tamsulosin showed the most prominent efficacy for the treatment of OAB compared to the naftopidil and combination. The combination of tamsulosin with naftopidil showed no synergistic effects on OAB; however, further studies of addon therapy might provide opportunities to find a new modality.

Randomized Controlled Trial to Compare the Safety and Efficacy of Naftopidil and Tamsulosin as Medical Expulsive Therapy in Combination With Prednisolone for Distal Ureteral Stones

PURPOSE: To compare the safety and efficacy of naftopidil and tamsulosin with prednisolone as medical expulsive therapy for distal ureteric stones. MATERIALS AND METHODS: Between July 2010 and March 2012, 120 adult patients presenting with distal ureteric stones of size 5 to 10 mm were randomized equally to tamsulosin (group A), naftopidil (group B) or watchful waiting (group C). Tamsulosin or naftopidil was given for a maximum of four weeks. In addition patients in group A and B were given 5 mg prednisolone once daily (maximum one week). Stone expulsion rate, time to stone expulsion, analgesic use, number of hospital visits for pain, follow-up and endoscopic treatment and adverse effects of drugs were noted. Statistical analyses were done using chi-square test, Mann-Whitney test and analysis of variance. RESULTS: There was a statistically higher expulsion rate in groups A (70%) and B (87.5%) as compared to group C (32.5%) (p<0.001). The expulsion rates were not statistically different between groups A and B (p=0.056). The mean time to expulsion was comparable between groups A and B but longer in group C. Analgesic use was significantly lower in groups A and B. Average number of hospital visits for pain, follow-up and endoscopic treatment was similar in all groups. There was no serious adverse event. CONCLUSIONS: Medical expulsive therapy for the distal ureteric stones using either naftopidil or tamsulosin in combination with prednisolone is safe and efficacious.

Evaluation of clinical effect of ZeGuiLongShuang capsules combined with naftopidil on benign prostatic heperplasia / 吉林大学学报(医学版)

Objective To study the curative effect of ZeGuiLongShuang capsules combined with naftopidil on benign prostatic hyperplasia(BPH).Methods 140 cases with BPH were randomly divided into treatment group and control group.The patients in treatment group were given ZeGuiLongShuang capsules(once 2 tablets,3 times a day) combined with naftopidil(once 25 mg,once a day before sleeping).The patients in control group were given only naftopidil(once 25 mg,once a day before sleeping).Internatianal-prognosic-scoring-system(IPSS),uroflowmetry-max(Qmax),Quality-of-life(QOL),residual urine and weight of prostate before and after treatment were detected.Results IPSS,Qmax,QOL and residual urine changed in two groups.IPSS,Qmax,QOL and residual urine in treatment group were more significant than those in control group(P

Effects of Naftopidil' ramification-BWYJ on intracellularlar free Ca~(2+) in smooth cells / 中国临床药理学与治疗学

AIM: To observed the effects of BWYJ (a naftopidil ramification) on intracellularlar free Ca~(2+)([Ca~(2+)]_i) in smooth cells (SMCs) in order to further explore its vasodilative mechanisms. METHODS: The [Ca~(2+)]_i was determined with the Fura-2/AM loaded SMCs in aorta of rabbit, and the effects of BWYJ on the elevation induced by NA, and high potassium and 5-HT were observe. RESULTS: In the Fura-2/AM loaded SMCs, BWYJ had no effect on the resting [Ca~(2+)]_i, but it reduced the increase of [Ca~(2+)]_i induced by NA and 5-HT, and there was no influence on the increase of [Ca~(2+)]_i induced by high potassium. CONCLUSION: The vasodilative mechanisms of BWYJ may be related to its inhibitive effects on the Ca~(2+)-influx and Ca~(2+)-release mediated by ?_1- and 5-HT_(2A) receptors. It inhibits the release of intracellular calcium, and the result is it decrease the [Ca~(2+)]_i in SMCs.

The efficacy of naftopidil in treatment of female urethral syndrome / 医学研究生学报

Objective: To evaluate the efficacy and safety of Naftopidil on patients with female urethral syndrome (FUS). Methods: Self-controlled clinical trial was performed in patients with FUS. Thirty-eight patients were treated with naftopidil tablet 25mg/po/qn for 4 weeks after one-week washout period. The effects were evaluated mainly by female urethral syndrome score (FUSS) and quality of life (QOL). Results: FUSS began to decrease after 2 (week's) administration and decreased significantly after 4 weeks' treatment. It had statistically significant difference of FUSS and QOL after treatment compared with control (P

Effects of YMⅢ on vascular contractive activities and the underlying mechanism / 中国药理学通报

Aim To investigate the effects of YMⅢ,a derivative of naftopidil, on the vascular contractive activities in rabbit aorta and to explore its vasodilative mechanisms.Methods The isotonic contractions of the thoracic aorta strips from rabbits were recorded, and the effects of YMⅢ on the concentration-response curves of noradrenaline(NA),high potassium and 5-hydroxytryptamine(5-HT)were observed.Intracellular free Ca2+([Ca2+]i)was investigated in the pressence of and the absence of YMⅢ in different conditions.Results YMⅢ(10-8,5?10-8,10-7 mol?L-1)shifted the concentration-response curve of NA with a parallel manner to right, the maximum response was unchanged and the pA2 value was 8.00; YMⅢ (10-5 mol?L-1)also shifted the concentration-response curve induced by high potassium to right but with non-parallel manner,the response was depressed and the pD′2 value was 4.26. However, YMⅢ(10-7,10-6,10-5 mol?L-1)had no statistical influence on the concentration-response curve induced by 5-HT, although it tended to depress the response of the curve at 10-5 mol?L-1.In Ca2+-free medium,YMⅢ (10-8,5?10-8 and 10-7mol?L-1) significantly inhibited the transient contraction induced by NA and the long-lasting one induced by addition of Ca2+ with a concentration-dependent manner.But even at 10-5 mol?L-1,it did not inhibit the contraction induced by caffeine.Conclusions YMⅢ may be ?-adrenergic receptor blocker.Its vasodilative mechanism may be related to:blocking ?-adrenergic receptor on cell membrane resulting in the inhibition on the influx of extracellular Ca2+ and the release of intracellular calcium.

The antiproliferation effect of naftopidil in vascular smooth muscle cells of rats / 中国药理学通报

Aim To study the effect of naftopidil(Naf) on noradrenalin(NA)-induced proliferation of rats vascular smooth muscle cells (VSMCs),and explore its mechanisms. Methods The cultured VSMCs was induced to proliferate by NA,and effects of Naf on the VSMCs proliferation was tested by MTT assay and cell counting method respectively. The intra-cellular calcium concentration is investigated by fluorimetry,and the expressions of c-myc,c-fos and hypertension related gene-1(HRG-1) mRNA were tested by Real-Time RT-PCR. Results The proliferation of VSMCs induced by NA was inhibited by Naf(10-7~10-6mol?L-1),which diminished clearly VSMCs [Ca2+]i and decreased mRNA expressions of c-myc,c-fos and increased the expression of HRG-1 mRNA. Conclusions Proliferation of VSMCs induced by NA can be inhibited clearly by Naf. The mechanisms may be related to diminishing [Ca2+]i,antagonizing the up-regulation of c-myc and c-fos mRNA expressions by NA and antagonizing the down-regulation of HRG-1 mRNA expression.

Circulatory levels of hormones and cytokines in the patients with chronic heart failure and the effect of naftopidil / 中国实用内科杂志

Objective To investigate the circulatory levels of hormones and cytokines in the patients with the chronic heart failure(CHF)and the effect of naftopidil.Methods The levels of tumor necrosis factor-?(TNF-?),interleukin-1(IL-1),interleukin-6(IL-6),endothelin-1(ET-1),adrenomedullin(Adm),neuropeptide Y(NPY),calcitonin gene-related peptide(CGRP),atrial natriuretic peptide(ANP),brain natriuretic peptide(BNP)and C-type natriuretic peptide(CNP),and left ventricular fraction(LVEF)of 47 patients with CHF(CHF group)and 24 healthy subjects(control group)were measured by radioimmunoassay or echocardiography respectively.The patients were randomized to receive naftopidil(50mg Bid)in addition to routine therapy(B group,n=23)or routine therapy only(A group,n=24)for one-month.Results (1)The levels of TNF-?,IL-1,IL-6,ET-1,Adm,NPY,ANP,BNP and CNP of the CHF group were higher(P 0.05)in the levels of IL-1,IL-6,Adm,CNP and LVEF.(4)There were significantly inverse correlations between LVEF and TNF-?,ET-1,IL-6 or BNP(P

Clinical study of naftopidil,a new type of ?_1-adrenoceptor antagonist for treatment of benign prostatic hyperplasia / 中华泌尿外科杂志

Objective To study the efficacy and safety of naftopidil,a new ? 1-adrenoceptor antagonist for treatment of benign prostatic hyperplasia(BPH). Methods A randomized,double-blind,double-simulant,parallel-controlled,multicentral clinical trial was conducted in 224 patients with BPH.Patients of treatment group received naftopidil (25 mg,once a day) and the controls received tamsulosin (0.2 mg,once a day). Results After 6-week therapy,IPSS,quality of life (QOL) score,maximum urinary flow rate (Qmax) and average urinary flow rate(Qave) were significantly improved both in naftopidil group and tamsulosin (control) group.In naftopidil group,IPSS was averagely decreased by 11.03 (P0.05).The clinical adverse event rate was 2.68% in naftopidil group, which was significantly lower than that in tamsulosin group (8.93%,P

Bioequivalence of naftopidil capsule vs tablet in Chinese healthy male volunteers / 中国临床药理学与治疗学

AIM: To study the pharmacokinetics and rela ti ve bioavailability of naftopidil in healthy male volunteers. METHODS: The naftopidil concentrations in plasma were determined by HPLC. The test and reference formulations of naftopidil were given to 18 healthy male volunteer s. The calibration curve was linear within the range of 1.6 - 400 ?g?L -1 , r=1. The minimum detection limit was 1 ?g?L -1 . The mean recovery rate was 85.2 %- 89.9 %, RSDs of inter-day and i ntra-day were no more than 8.0 %. RESULTS: After a single o ral dose of 50 mg naftopidil test capsules or reference tablets, the main pharma cokinetic parameters AUC 0-24 : 295.6 ? 90.9 and 291.6 ? 89.3 ?g?L -1 ?h -1 ; AUC 0-∞ : 320.0 ? 97.2 and 318.0 ? 98.3 ?g?L -1 ?h -1 ; T max : 0.6 ? 0.2 and 0 .6 ? 0.2 h ; C max : 129.1 ? 60.7 and 138.3 ? 72.5 ?g? L -1 ; T 1/2 : 5.9 ? 1.7 and 6.4 ? 2.1 h , respectively. The relative bioavailability F 0-24 ,F 0-∞ were 101.9 ? 12.9 % and 101.2 ? 12.3 %, respectively. CONCLUSION: No signifi cant difference exists among the pharmacokinetic parameters for the test capsule s and the reference tablets of naftopidil. The two formulations were bioequivale nt.

Study on the Pharmacokinetics of Naftopidil Sustained-release Capsule in Dogs / 中国药房

OBJECTIVE:To study the pharmacokinetics and the bioavailability of naftopidil sustained-release capsules. METHODS:Naftopidil capsule and sustained-release capsules were given to five healthy male dogs respectively in an open randomized cross-over test.Naftopidil concentrations in plasma were determined by HPLC method.The pharmacokinetics parameters and the relative bioavailability were measured and compared between naftopidil capsules and sustained-release capsules.RESULTS:A one-compartment open model with first-order absorption kinetics best fitted the concentration-time data.The T 1/2 ,AUC 0～∞ ,C max and T max of naftopidil capsule were3.2?1.1h,3728.1?573.1ng?h/ml,697.5?94.2ng/ml and1.2?0.59h,these pharmacokinetics parameters of sustained-release capsules were5.9?0.8h,5518.3?391.1ng?h/ml and468.6?61.3ng/ml and4.0?0.7h respectively.The relative bioavailability of naftopidil sustained-release capsules was149.8?14.4%when compared with naftopidil capsules.CONCLUSION:Naftopidil sustained-release capsules have satisfactory property in slow release of drug and much higher bioavailability than naftopidil capsules.