Earticle

A new medical system was started in Korea in 2000 and pharmaceutical affairs law was revised in 2001. According to the revised law, generic substitution is permitted only to therapeutically equivalent generic product. Bioequivalence studies are usually used to demonstrate therapeutic equivalence between reference listed drugs and generic drugs. The issues that are recently heating up in Korea are to increase bioequivalent drug products and at the same time to ensure the credibility of the therapeutic equivalence of generic drugs. Sometimes food can change the bioavailability (BA) of a drug and influence the bioequivalence (BE) between test and reference products as well. Food effects on BA can have clinically significant consequences. Food can alter BA by various means including delaying gastric emptying, stimulating bile flow and changing gastointestinal pH. This paper provides the recently published Korean guideline on food-effect BA and fed BE studies.

항혈소판제인 티크로피딘과 항고혈압제인 니칼디핀과의 약동학적 상호작용 연구를 위하여 티크로피딘 (3 또는 10 mg/kg) 과 니칼디핀의 경구 (4 mg/kg) 및 정맥 (12 mg/kg) 투여하여 본 연구를 시행하 였다. 연구방법: 티크로피딘이 cytochrome P450 (CYP) 3A4 활성과 P-glycoprotein (P-gp)의 활성에 미치는 영향도 평가 하였다. 결 과: 티크로피딘과 니칼디핀의 병용투여 시 티크로피딘이 니칼디핀의 약물동태 파라미터에 미치는 결과는 다 음과 같다. 티크로피딘은 CYP3A4 효소의 활성을 저해 하였으나 P-gp활성에는 영향을 미치지 못하였다. 니칼디핀의 혈 중농도곡선하면적 (AUC)는 대조군에 비해 티크로피딘 10 mg/kg 병용투여군에서 유의성 (p < 0.05)있게 증가되었다. 상 대적 생체이용률 (RB)은 티크로피딘 병용 투여군에서 115-143%로 증가하였다. 결 론: 본 논문에서 흰쥐에 티크로피딘 과 니칼디핀을 병용경구투여 시 니칼디핀 의 생체이용률 (bioavailability)이 유의성 (p < 0.05)있게 증가된 것은 티크로피 딘이 대사효소인 CYP3A4를 억제하여 소장과 간장에서 초회통과효과 (first-pass metabolism)를 감소 시켰기 때문 인 것으로 사료된다. 본 실험결과를 토대로 인체에서 티크로피딘과 니칼디핀의 상호작용을 검토한 후 투여용량을 조절하 는 것이 바람직하다고 사료된다.

에토포시드와 아피제닌의 약동학적 상호작용 연구를 위하여 아피제닌 (0.4, 2.0 또는 8 mg/kg)과 에토포시드의 경구(6 mg/kg) 및 정맥 (2 mg/kg) 투여 하여 본 연구를 실시하였다. 아피제닌이 cytochrome P450 (CYP) 3A4 활성과 P-glycoprotein (P-gp)의 활성에 미치는 영향도 평가하였다 아피제닌의 CYP3A4의 50% 효소활성억제는 1.8 μM 이었다. 아피제닌은 MCF-7/ADR 세포의 로다마인-123 세포 축적을 증가 시키므로 P-gp를 억제시켰다. 아피제닌은 에토포시드의 혈장곡선하면적과 최고혈장농도 (AUC and Cmax)를 유의성 있게 증가시켰으나, 에토포시드의 최고혈장농도 도달시간 (Tmax)과 생물학적 반감기 (t1/2)에는 영향을 미치지 않았다. 따라서, 아피제닌 존재하에 에토포시드의 절대적생체이용률 (AB)은 대조군과 비교하여 유의성있게 증가되었다. 경구투여시와는 대조적으로, 아피제닌은 정맥 내로 투여된 에토포시드에서는 약동학적 파라미터에 어떤 영향도 미치지 않았다. 따라서 아피제닌이 에토포시드의 생체이용률을 증가시킨 것은 아피제닌이 소장과 간장에서 CYP3A4을 억제 및 소장에서 P-gp를 억제 시켰기 때문으로 사료된다.

Tacrolimus, an immunosuppressant prescribed against graft-versus-host disease (GVHD) in patients with allogeneichematopoietic stem cell transplantation (HSCT), is affected to change its pharmacokinetic properties by various factors. For this reason, it is needed a close monitoring to adjust dosage amount in order to optimize the blood concentration of tacrolimus is located within the effective range. According to our in-house study, 62% of HSCT-patients were needed dosage-adjustment and it is necessary to optimize the current immunosuppressive regimen in clinical settings. A retrospective study was designed to evaluate the dosing regimen (converting ratio of IV:PO=1:4) of tacrolimus in HSCT patients (n=62). After collecting data from patient’s profile and medical record, pharmacokinetic parameters were calculated and compared between the estimated and the actual values in the selected subjects (n=58). It was found that the bioavailabilty (BA) of oral tacrolimus was 40.5% very much different from that is known as 25%. It implies that the current protocol has a potent risk causes dose-related toxicities to the patients. Furthermore, analyses among factors demonstrated that there was no statistical significance between BA of tacrolimus and the variable factors. In the clinical perspectives, the current converting ratio of tacrolimus in patients with HSCT to be re-considered and an appropriate and optimal alternative regimen should be adopted to prevent GVHD and to increase the quality of life of patients.

The purpose of this study is to investigate the effect of aspirin on the pharmacokinetics of pranoprofen by oral coadministration of pranoprofen (5 mg/kg) with aspirin (5, 10 and 20 mg/kg) in Sprague-Dawley rats. After oral coadministration of pranoprofen with aspirin, the area under the plasma concentration-time curves (AUC) of pranoprofen was increased significantly by 10 mg/kg (p<0.05) and 20 mg/kg (p<0.01) of aspirin coadministration, and peak concentrations () of pranoprofen was increased significantly by coadministration of 20 mg/kg aspirin (p<0.05) compared to pranoprofen alone. Relative bioavailabilities (RB) of pranoprofen in coadmistration were higher (from 1.42 to 1.67 fold) than control. The half-lives () of pranoprofen in coadministration were increased significantly (p<0.05) by 20-mg/kg aspirin. Based on these results, we might be considered that the pharmacokinetics of pranoprofen would be affected by coadministration of aspirin, by inhibit its metabolism in the liver and the tubular secretion of the kidney with the same acidic property. It should take into consideration in dosage regimen of pranoprofen when coadministration of pranoprofen with aspirin in treatment of rheumatoid arthritis.

The aim of this study is to investigate the effect of naringin on the pharmacokinetics of tamoxifen in rats. Tamoxifen (10 mg/kg) was administered orally 0.5 h and 3 days after oral administration of naringin (5 mg/kg). The plasma concentrations of tamoxifen were increased significantly tv naringin compared to control. Absorption rate constant () of tamoxifen with naringin was increased significantly compared to that of the control. The areas under the plasma concentration-time curve (AUC) and the peak concentrations () of tamoxifen with naringin were significantly higher than those of the control. Consequently, the relative bioavailability (R.B) of tamoxifen with naringin was 2-3-fold higher than the control, and absolute bioavailability (A.B) of tamoxifen were significantly higher (p<0.05 with coadministration, p<0.01 with pretreatment) than those of the control. The increased bioavailability of tamoxifen in rats with naringin might be associated with the inhibition by naringin of an efflux pump P-glycoprotein and the first-pass metabolizing enzyme CYP3A4.

In an effort to improve ginsenoside bioavailability, the ginsenosides of fermented red ginseng were examined with respect to bioavailability and physiological activity. The results showed that the fermented red ginseng (FRG) had a high level of ginsenoside metabolites. The total ginsenoside contents in non-fermented red ginseng (NFRG) and FRG were 35715.2 ${\mu}g$/mL and 34822.9 ${\mu}g$/mL, respectively. However, RFG had a higher content (14914.3 ${\mu}g$/mL) of ginsenoside metabolites (Rg3, Rg5, Rk1, CK, Rh1, F2, and Rg2) compared to NFRG (5697.9 ${\mu}g$/mL). The skin permeability of RFG was higher than that of NFRG using Franz diffusion cells. Particularly, after 5 hr, the skin permeability of RFG was significantly (p<0.05) higher than that of NFRG. Using everted instestinal sacs of rats, RFG showed a high transport level (10.3 mg of polyphenols/g sac) compared to NFRG (6.67 of mg of polyphenols/g sac) after 1 hr. After oral administration of NFRG and FRG to rats, serum concentrations were determined by HPLC. Peak concentrations of Rk1, Rh1, Rc, and Rg5 were approximately 1.64, 2.35, 1.13, and 1.25-fold higher, respectively, for FRG than for NFRG. Furthermore, Rk1, Rh1, and Rg5 increased more rapidly in the blood by the oral administration of FRG versus NFRG. FRG had dramatically improved bioavailability compared to NFRG as indicated by skin permeation, intestinal permeability, and ginsenoside levels in the blood. The significantly greater bioavailability of FRG may have been due to the transformation of its ginsenosides by fermentation to more easily absorbable forms (ginsenoside metabolites).

Tomatoes and tomato products are the major source of lycopene in the diet. The bioavailability of lycopene is different in raw tomatoes compared to processed tomato products. This is due to the chemical and physical properties of the different lycopene isomers. All-trans-lycopene is found in raw tomatoes and is a poor bioavailable source, whereas, processed tomato products are more bioavailable because they contain more cis-isomers. Heat and mechanical processing of tomatoes induces rupture of the cell walls, thereby releasing lycopene from its food matrix. Heat processing also induces cis-trans isomerization and disrupts protein-carotenoid complexes. Many dietary components also impact lycopene bioavailability, like the amount and type of fat present with the intake and processing of tomato products, the amount and type of fiber present, and the interaction between carotenoids. Fundamentally, anything that enhances formation and incorporation of lycopene in bile acid micelles increases bioavailability, and the opposite is true in that anything that interferes with micelle formation decreases bioavailability.

Tea is a pleasant, popular and safe beverage in the world. During the past decade, epidemiological studies have shown that tea catechins intake is associated with lower risk of cardiovascular disease. Tea provides a dietary source of health-promoting components to help humans reduce a wide variety of cancer risks and chronic diseases. The antioxidative activity of tea-derived catchins has been extensively studied. The antioxidant effect is a synergistic action between catechins e.g. EGCG, EGC, ECG, EC, pheophytins a and b, and other components in tea leaves, which aye more bioavailable for human body. Green tea has a Higher content of catechins than other kinds of tea. Green tea extract with hot water has high potential and more efficiency to reduce cancer risk than any other tea products or pure EGCG. Protein, iyon, and other food components may interfere with the bioavailability of ten catechins. Interaction of catechins with drug affects the cancer-preventive activity of some cancer-fighting medication. Further studies are required to determine the bioavailability of tea catechins and cancer-preventive functionality.

The purpose of this study was to evaluate relative bioavailability of the coenzyme Q10 (CoQ10) in emulsion and three liposome formulations after a single oral administration (60 mg/kg) into rats. Emulsion formulation of CoQ10 was prepared by conventional method using Phospholipon 85G as an emulsifier, and three liposome formulations (neutral, anionic, and cationic) of CoQ10 were prepared by traditional lipid film hydration technique using Phospholipon 85G, cholesterol, and charge carrier lipids (1,2-dioleoyl-3-trimethylammonium-propane chloride salt for cationic liposome and 1,2-dimyristoyl-sn-glycero-3-phosphate monosodium salt for anionic liposome). Mean particle size of all CoQ10-loaded liposome was less than a micron, and size distribution of the liposome population was homogeneous. Bioavailability of CoQ10 in emulsion was 1.5 to 2.6-fold greater than liposome formulations in terms of $AUC_{0-24\;h}$. $T_{max}$ was 3 h when administered as emulsion while it was greater than 6 h in liposome formulations. Notably, it was approximately 8 h in cationic liposome. $C_{max}$ was highest in emulsion and was significantly decreased when administered as liposome. Charged liposome showed even lower $C_{max}$ than neutral liposome, especially in cationic liposome. In conclusion, therefore, it is suggested that clinicians and patients consider bioavailability issue a primary concern when choosing a CoQ10 product, especially when very high plasma level is required such as in the treatment of heart failure and Parkinson's disease.

The pharmacokinetics and bioavailability of ambroxol, an expectoration improver and mucolytic agent, were studied to determine the feasibility of enhanced transdermal delivery of ambroxol from the ethylene-vinyl acetate (EVA) matrix system containing polyoxyethylene-2-oleyl ether as an enhancer in rats. The ambroxol-010 matrix system (15 mg/kg) was applied to abdominal skin of rats. Blood samples were collected via the femoral artery for 28 hrs and the plasma concentrations of ambroxol were determined by HPLC. Pharmacokinetic parameters were calculated using Lagran method computer program. The area under the curve (AUC) was significantly higher in the enhancer group ($1,678{\pm}1,413.3\;ng/ml{\cdot}hr$) than that in the control group $1,112{\pm}279\;ng/ml{\cdot}hr$), that is treated transdermally without enhancer, showing about 151% increased bioavailability (p<0.05). The average $C_{max}$ was increased in the enhancer group ($86.0{\pm}21.5\;ng$/ml) compared with the control group ($59.0{\pm}14.8\;ng$/ml). The absolute bioavailability was 13.9% in the transdermal control group, 21.1% in the transdermal enhancer group and 18.1% in the oral administration group compared with the IV group. The $T_{max}$, $K_a$, MRT and $t_{1/2}$ of ambroxol in transdermal enhancer group were increased significantly (p<0.01) compared to those of oral administration. As the ambroxol-EVA matrix containing polyoxyethylene-2-oleyl ether and tributyl citrate was administered to rats via the transdermal routes, the relative bioavailability increased about 1.51-fold compared to the control group, showing a relatively constant, sustained blood concentration. The results of this study show that ambroxol-EVA matrix could be developed as a transdermal delivery system providing sustained plasma concentration.

The pharmacokinetic parameters and bioavailability of pranoprofen from the gel were measured to determine the enhancing effect of octanoic acid on the transdermal absorption of pranoprofen in rats. 8 mg/kg of pranoprofen was administered from gel with octanoic acid (the enhancer group) or that without octanoic acid (the control group) via the transdermal route, and the results were compared with those obtained from the intravenously (0.5 mg/kg, IV group) or orally administered group (4 mg/kg, oral group). The AUC of the control, the enhancer, the IV, and the oral groups were $20.2{\pm}5.1$, $50.7{\pm}12.7$, $19.9{\pm}2.5$, and $70.5{\pm}17.6\;ug/ml{\cdot}h$ respectively. The average $C_{max}$ of the control and the enhancer group were $0.93{\pm}0.23$ and $2.82{\pm}0.71\;ug/ml$, respectively, and the mean $T_{max}$ of the control and the enhancer group was 7.00 h. The relative bioavailability of the transdermally administered pranoprofen gel containing octanoic acid was approximately 2.50 times higher than the control group, showing a relatively constant, sustained blood concentration with minimal fluctuation. This suggests that it might be feasible to develop a pranoprofen gel preparation containing an enhancer for the transdermal administration, which is more convenient dosage form than the oral dosage forms.

This study aimed to compare the changes in the bioactivities of peptide extracts (< 10 kDa) obtained from Jeju black pigs (JBP) and three-way crossbred pigs (Landrace × Yorkshire × Duroc, LYD) before and after digestion. The results showed that the loin peptide extracts of JBP maintained high 2,2’-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical scavenging activity after in vitro digestion. However, the iron chelating activity and antihypertensive activity of all peptide extracts were decreased. This study suggested that the peptide extracts produced through alkaline-AK digestion have sufficiently high antioxidant and antihypertensive activities; however, these activities were reduced after in vitro digestion. Meanwhile, the JBP loin and ham peptide extracts promoted high superoxide dismutase (SOD) activity than that of LYD when administered to mice. Furthermore, the ham peptide extracts of JBP showed a relatively high antihypertensive activity in mice. Therefore, it is deemed that these peptide extracts from JBP are more bioactive than that of LYD, and can be used as bioactive materials.

Using antibiotics as growth promoter has been banned in poultry feed industry, thus various researchers try to seek an alternative to replace the growth-promoting antibiotics. In this study, we aimed to evaluate the growth performance via intestinal nutrient utilization and cecal microbial composition of broiler after dietary supplementation with most commonly using antibiotics, zinc bacitracin, and sophorolipid. A total of 180 1-day-old chicks were randomly assigned, and dietary treatment was as follow: CON, basal diet; ZB, 100 ppm of zinc bacitracin supplemented diet; and SPL, 250 ppm of sophorolipid supplemented diet. Their growth performance was evaluated and the samples of blood, small intestine, and ileal and cecal digesta were collected for biochemical, histological, and genomic analyses. The body weight and average daily gain of 7-day-old chicks were higher in ZB and those in overall experimental period were improved by ZB and SPL supplementation (p < 0.05). Their intestinal characteristics were not affected by dietary treatments in duodenum and ileum. Nonetheless, villus height was increased by SPL supplementation in jejunum (p < 0.05). Moreover, dietary SPL supplementation could down-regulate the expression level of pro-inflammatory cytokine, IL-1β (p < 0.05). mRNA levels of lipid and protein transporters did not differ among the treatments, however, relative expression levels of carbohydrate transporters, GLUT2 and SGLT1 were increased in broiler chicken’s jejumum fed zinc bacitracin and sophorolipid supplemented diets (p < 0.05). Dietary zinc bacitracin supplementation could increase the population of Firmicutes in phylum level, and the portion of Turiciacter in genus level. On the other hands, the portion of Faecalibacterium was increased by dietary SPL supplementation compared to the other treatments. Our findings suggest that SPL supplementation improves growth performance through enhanced carbohydrate utilization capacity via improvement of gut morphological status and modulation of the cecal microbial population of broilers.

The objective of this study was to enhance the oral bioavailability (BA) of zanamivir (ZMR) by increasing its intestinal permeability using permeation enhancers (PE). Four different classes of PEs (Labrasol$^{(R)}$, sodium cholate, sodium caprate, hydroxypropyl ${\beta}$-cyclodextrin) were investigated for their ability to enhance the permeation of ZMR across Caco-2 cell monolayers. The flux and $P_{app}$ of ZMR in the presence of sodium caprate (SC) was significantly higher than other PEs in comparison to control, and was selected for further investigation. All concentrations of SC (10-200 mM) demonstrated enhanced flux of ZMR in comparison to control. The highest flux (13 folds higher than control) was achieved for the formulation with highest SC concentration (200 mM). The relative BA of ZMR formulation containing SC (PO-SC) in plasma at a dose of 10 mg/kg following oral administration in rats was 317.65% in comparison to control formulation (PO-C). Besides, the $AUC_{0-24\;h}$ of ZMR in the lungs following oral administration of PO-SC was $125.22{\pm}27.25$ ng hr $ml^{-1}$ with a $C_{max}$ of $156.00{\pm}24.00$ ng/ml reached at $0.50{\pm}0.00$ h. But, there was no ZMR detected in the lungs following administration of control formulation (PO-C). The findings of this study indicated that the oral formulation PO-SC containing ZMR and SC was able to enhance the BA of ZMR in plasma to an appropriate amount that would make ZMR available in lungs at a concentration higher (>10 ng/ml) than the $IC_{50}$ concentration of influenza virus (0.64-7.9 ng/ml) to exert its therapeutic effect.

This study was to investigate the effect of apigenin on the bioavailability of paclitaxel after oral and intravenous administration in rats. The effect of apigenin on P-glycoprotein (P-gp), cytochrome P450 (CYP)3A4 activity was evaluated. The pharmacokinetic parameters of paclitaxel were determined in rats after oral (40 mg/kg) or intravenous (5 mg/kg) administration of paclitaxel with apigenin (0.4, 2 and 8 mg/kg) to rats. Apigenin inhibited CYP3A4 activity with 50% inhibition concentration ($IC_{50}$) of 1.8 ${\mu}M$. In addition, apigenin significantly inhibited P-gp activity. Compared to the control group, apigenin significantly increased the area under the plasma concentration-time curve (AUC, p<0.05 by 2 mg/kg, 59.0% higher; p<0.01 by 8 mg/kg, 87% higher) of oral paclitaxel. Apigenin also significantly (p<0.05 by 2 mg/kg, 37.2% higher; p<0.01 by 8 mg/kg, 59.3% higher) increased the peak plasma concentration ($C_{max}$) of oral paclitaxel. Apigenin significantly increased the terminal half-life ($t_{1/2}$, p<0.05 by 8 mg/kg, 34.5%) of oral paclitaxel. Consequently, the absolute bioavailability (A.B.) of paclitaxel was significantly (p<0.05 by 2 mg/kg, p<0.01 by 8 mg/kg) increased by apigenin compared to that in the control group, and the relative bioavailability (R.B.) of oral paclitaxel was increased by 1.14- to 1.87-fold. The pharmacokinetics of intravenous paclitaxel were not affected by the concurrent use of apigenin in contrast to the oral administration of paclitaxel. Accordingly, the enhanced oral bioavailability by apigenin may be mainly due to increased intestinal absorption caused via P-gp inhibition by apigenin rather than to reduced renal and hepatic elimination of paclitaxel. The increase in the oral bioavailability might be mainly attributed to enhanced absorption in the gastrointestinal tract via the inhibition of P-gp and reduced first-pass metabolism of paclitaxel via the inhibition of the CYP3A subfamily in the small intestine and/or in the liver by apigenin. It appears that the development of oral paclitaxel preparations as a combination therapy is possible, which will be more convenient than the i.v. dosage form.

${\beta}$-Lapachone has drawn increasing attention as an anti-inflammatory and anti-cancer drug. However, its oral bioavailability has not been yet assessed, which might be useful to develop efficient dosage forms possibly required for non-clinical and clinical studies and future market. The aim of the present study was thus to investigate pharmacokinetic properties of ${\beta}$-lapachone as well as its first-pass metabolism in the liver, and small and large intestines after oral administration to measure the absolute bioavailability in rats. A sensitive HPLC method was developed to evaluate levels of ${\beta}$-lapachone in plasma and organ homogenates. The drug degradation profiles were examined in plasma to assess the stability of the drug and in liver and intestinal homogenates to evaluate first-pass metabolism. Pharmacokinetic profiles were obtained after oral and intravenous administration of ${\beta}$-lapachone at doses of 40 mg/kg and 1.5 mg/kg, respectively. The measured oral bioavailability of ${\beta}$-lapachone was 15.5%. The considerable degradation of ${\beta}$-lapachone was seen in the organ homogenates but the drug was quite stable in plasma. In conclusion, we suggest that the fairly low oral bioavailability of ${\beta}$-lapachone may be resulted from the first-pass metabolic degradation of ${\beta}$-lapachone in the liver, small and large intestinal tracts and its low aqueous solubility.

This study was aimed to investigate the Cu bioavailability, growth response, digestibility of nutrients, and blood metabolites of broiler chicks fed CuSO4 in nano or common forms. A total of 720 broiler chickens were distributed between eight treatments according to a completely randomized design. There were 8 treatments and 6 replicates in each treatment with 15 birds/replicate. The treatments were divided into common copper sulfate at the doses of 16 ppm, 40 ppm, 80 ppm, and 120 ppm (INO) and hot-melt extruded copper sulfate at the doses of 16 ppm, 40 ppm, 80 ppm, and 120 ppm (HME-Cu). The experiment was operated for 35 days in 2 phases (phase 1, d 0 to 14; and phase 2, d 15 to 35). No significant differences were shown in growth performance, feed intake, FCR, and nutrient digestibility among the treatments. The concentration of Cu in the serum was increased in the HME-Cu broilers compared with the INO broilers at phase 2. A linear increase was observed in the concentration of Cu in the liver in broilers fed INO diets, however, no significant differences were observed by the supplementation of HME-Cu levels. The linear increase was detected in the content of Cu in excreta in the INO and HME-Cu treatments by increasing the dietary Cu content. The HME-Cu treatments showed a lower Cu concentration in the excreta compared with the INO treatments. The higher bioavailability of Cu in HME form can decrease the recommended dose of Cu in broiler diets.

Background: Rice bran is a by-product of the rice-milling process, which remains largely underutilized; however, efficient processing treatments may improve its feeding value for chickens. This is of great economic and environmental importance, as this can lower the production costs, and offer an opportunity for valorization of a low-quality agricultural by-product, to a high-value feed source. Methods: This experiment was conducted to study the effect of extruded rice bran on performance and phosphorous (P) bioavailability in broiler chickens. In a completely randomized design, 200 seven-day-old broilers (Cobb 500) were allotted to five treatments with five replicates per treatment and 8 chicks per replicate, and fed with their respective diet during the starter (8 to 21 days) and grower (22 to 42 days) periods. Diets were a basal corn-soybean based diet (T1), or diets containing 20 % rice bran (T2), 30 % rice bran (T3), 20 % extruded rice bran (T4), or 30 % extruded rice bran (T5). Results: Birds feeding on T4 and T5 diets had a higher body weight gain and lower feed-to-gain ratio compared to those feeding on T2 and T3 diets (p < 0.05). Birds receiving diets containing extruded rice bran had higher total P availability and tibia ash content, as compared with those receiving diets containing un-extruded rice bran (p < 0.05). Relative weight of the pancreas was higher in birds receiving T2 and T3 diets. Conclusions: The results confirmed the beneficial effect of extrusion treatment of rice bran on performance and P availability in broilers. Up to 30 % extruded rice bran may be included in the broiler diet without apparent adverse effects on the performance.