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Rapid and Simple Method for the Determination of Pregabalin in Human Plasma using Liquid Chromatography-tandem Mass Spectrometry (LC-MS/MS): Application to a Bioequivalence Study of Daewoong Pregabalin Capsule To Lyrica® Capsule (Pregabalin 150 mg)

  • Jang, Ki-Ho;Seo, Ji-Hyung;Yim, Sung-Vin;Lee, Kyung-Tae
    • Journal of Pharmaceutical Investigation
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    • v.41 no.4
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    • pp.255-262
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    • 2011
  • Method using liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) was developed and validated for the determination of pregabalin in plasma samples. Acquisition was performed by monitoring the transitions: m/z 160.1${\rightarrow}$142.2 for pregabalin and m/z 423.2${\rightarrow}$207.1 for losartan (as an internal standard). After cold acetonitrileinduced protein precipitation of the plasma samples, separation was performed with C18 column by isocratic mobile phase consisted of 10 mM ammonium acetate and acetonitrile (15:85, v/v). Results were linear over the concentration ranged from 0.1 to $10{\mu}g$/mL and the correlation coefficients (r) were $\geq0.99$. Intra- and inter-day precisions were $\leq6.02$ and $\leq11.04%$, respectively, and intra- and inter-day accuracies were 96.60-101.09 and 98.10-102.60%, respectively. This validated method was successfully applied to a bioequivalence study of two formulations of pregabalin, Daewoong pregabalin capsule (Daewoong Pharm. Co., Ltd.) and Lyrica$^{(R)}$ capsule (Pfizer Korea Ltd.) in twenty eight healthy Korean volunteers. The subjects received a single oral dose of each formulation (150 mg as pregabalin) in a randomized $2{\times}2$ crossover study and plasma samples were obtained from each subject at predetermined time intervals. Then, the pharmacokinetic parameters ($AUC_{0-t}$, $C_{max}$ and $T_{max}$) were calculated and statistically analyzed to assess the differences between two formulations. The 90% confidence intervals for the log-transformed data were acceptable range of log 0.8-log 1.25 (e.g., log 1.0048-log 1.0692 for AUC0-t, log 0.9142-log 1.0421 for $C_{max}$). Thus, $AUC_{0-t}$ and $C_{max}$ met the criteria of the Korea Food and Drug Administration (KFDA) for bioequivalence test indicating that Daewoong pregabalin capsule was bioequivalent to Lyrica$^{(R)}$ capsule.

Effects of Methacrylamide Treatment on Silk Fibers III. Polymerization Behavior of Methacrylamide (견섬유에 대한 메타크릴아미드의 처리효과 III. 메타크릴아미드의 중합거동)

  • 신봉섭;남중희
    • Journal of Sericultural and Entomological Science
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    • v.34 no.2
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    • pp.32-40
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    • 1992
  • Many studies have been carried out on the graft finishing in order to improve the quality of silk fiber. Various vinyl monomers, for instance, styrene, methylmethacrylate, 2-hydroxyeth-ylmethacrylate and methacrylamide, have been used practically up to date. Among these monomers, methacrylamide has been applied as the most favourable monomer onto silk fibers in recent years. The polymerization mechanism about styrene- and methylmethacrylate-grafted silk fiber has been studied by many researchers. They proposed that free radicals were formed and vinyl monomers were polymerized in silk fibroin by graft polymerization mechanism, while active sites were varied by the types of monomer and initiator as well as by the reaction condition. In general. there is another Opinion that monomers are polymerized and impregnated in the internal side of the fiber by homopolymerization, which has not been proved experimentally yet More than 10 years have been passed since methacrylamide was applied on the silk fiber, and at the present time most finishings are being achieved by methacrylamide. However, no attention has been paid to the polymerization mechanism of the methacrylamide-treated silk fiber yeL In this paper, the treatments of methacrylamide on silk fibers were studied in aqueous solution using potassium persulfate as an initiator. The polymerization mechanism of the methacrylamide-treated silk fibers was investigated and analyzed on the basis of the results of infrared spectroscopy, amino acid analysis and scanning electron microscopy. From the results of these instrumental analyses, it can be suggested that polymerization mechanism about the methacrylamide-treated silk fibers is not performed by graft polymerization which has been accepted generally in styrene and methylmethacrylate-grafted silk fibers. The different mechanism is supposed to be due to the difference in monomer types, initiator types and treatment conditions.

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Effect of Seeds Treatment on Germinablity of Tetragonia Tetragonides Seeds (번행초의 대량번식을 위한 종자처리가 발아력에 미치는 영향)

  • Kang, Jum-Soon;Park, Eun-Ji;Kim, So-Hee;Heo, You;Park, Young-Hoon;Choi, Young-Whan;Son, Beung-Gu;Lim, Woo-Taik;Suh, Jeong-Min
    • Journal of Environmental Science International
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    • v.23 no.5
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    • pp.771-780
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    • 2014
  • Tetragonia tetragonides is a medicinal plant native to ocean sand soil of southern provinces and has significant effects on the prevention and curing of gastroenteric disorders. Despite of its popularity, supply of the plant has never met the level of demand because of the absence of an adequate culturing method. The present study, thereby, was conducted for classifying the plants with geographically different characteristics, studying growth habits, developing a new culturing method and establishing a large scale propagation system of selected superior individual plants. The study was also aimed for revealing optimum conditions for seed treatment, fertilization, and efficient culturing system and thereby, for utilizing the plant as a new income source for rural communities. The seed was elongated with size of 2.6 mm (width) ${\times}$ 1.8 mm (length). No difference in seed size was observed depending on different inhabitate. Each flower produced about 4.5~4.8 seeds. Germination rate was high for seeds matured for 40 days after fertilization, but deceased to 50% for seeds matured only for 20 or 30 days. Seed dormancy lasted 6 months and seed storage at humid $5^{\circ}C$ facilitated germination. Mechanical obstruct of seed germination was due to seed coat and removal of seed coat enhanced the germination rate. Optimum temp. for seed storage was $5^{\circ}C$, and high germination rate was maintained for 350 days. However, for stratification condition or at room temperature, germination was significantly reduced as storage time increased Optimum treatment of plant growth regulators was soaking in $GA_3$ 250 mg/L for 1 hr. The priming treatment with 50 mM $Ca(NO_3)_2$ at $20^{\circ}C$ for two days improved the seed germination with 10% compared to non-treated control. The treatment of 20% NaOCl for 3 hr. improved the seed germination rate up to 10% and 1 day ahead.

Effect of Dietary Lysine Restriction and Energy Density on Performance, Nutrient Digestibility and Meat Quality in Finishing Pigs

  • Jin, Y.H.;Oh, H.K.;Piao, L.G.;Jang, S.K.;Choi, Y.H.;Heo, P.S.;Jang, Y.D.;Kim, Y.Y.
    • Asian-Australasian Journal of Animal Sciences
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    • v.23 no.9
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    • pp.1213-1220
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    • 2010
  • This experiment evaluated the effects of dietary lysine restriction and energy density on growth performance, nutrient digestibility and meat quality of finishing pigs. A $2{\times}2$ factorial arrangement of treatments was utilized in a randomized complete block (RCB) design, and factor 1 was lysine restriction and factor 2 was energy density. The control diet was formulated to contain 3.265 Mcal of ME/kg, 0.75% lysine in the early-finishing phase and 3.265 Mcal of ME/kg, 0.60% lysine in the late-finishing phase and other nutrients met or exceeded NRC (1998) standards. Compared to the control diet (CON), lysine levels of experimental diets were restricted to 15% (treatment EL, EEL) or 30% (treatment ELL, EELL), whereas energy level of experimental diets was increased by 0.100 or 0.200 Mcal of ME/kg. A total of 100 crossbred pigs ([Yorkshire${\times}$Landrace]${\times}$Duroc), with average initial body weight of $58.47{\pm}1.42\;kg$, were allotted to 5 dietary treatments based on sex and body weight. Each treatment had 5 replicates with 4 pigs (two barrows and two gilts) per pen. ADG, ADFI and feed efficiency were calculated in an 8-week growth trial. In the late finishing period (5-8 weeks), pigs fed ELL or EELL diets had decreased ADG and feed efficiency (p<0.01), however, when the EEL diet was provided, a similar growth performance was observed compared to those fed the CON diet during the whole experimental period (p>0.05). In a metabolic trial, 15 pigs were used to evaluate the effect of dietary lysine restriction and energy density on nutrient digestibility. The digestibility of dry matter, crude fat and crude ash was not improved by restricting dietary lysine or energy density. However, crude protein digestibility was decreased (p<0.05) as dietary lysine was restricted. When dietary lysine was restricted, fecal nitrogen was increased whereas nitrogen retention was decreased. BUN concentration was affected by dietary lysine restriction; treatments ELL and EELL had higher BUN values than other treatments (p<0.01). Carcass characteristics and meat quality were measured when average body weight of pigs reached $107.83{\pm}1.50\;kg$. Treatment ELL had higher last rib backfat depth (p<0.05) than treatment CON, but ELL and EEL did not differ significantly. The ELL and EEL treatments had higher (p<0.05) subjective marbling score than treatment CON. Treatment EEL showed higher longissimus fat content than treatment EL and CON (p<0.01). The results indicated that finishing pigs fed a diet with 15% lysine restriction and 3.465 Mcal of ME/kg energy density had no detrimental effects on growth performance and N utilization, and could achieve substantial increases in marbling and longissimus fat content of pork.

Determination of Terazocin in Human Plasma by Liquid Chromatography and Bioequivalence Study of Teratonin® Tablets (액체크로마토그래프법에 의한 사람 혈장 중 테라조신의 정량 및 테라토닌® 정의 생물학적 동등성)

  • Cho, Eun-Sook;Kang, Sung-Ha;Chun, In-Koo
    • Journal of Pharmaceutical Investigation
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    • v.32 no.2
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    • pp.119-125
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    • 2002
  • A rapid, selective and reproducible high-performance liquid chromatographic method has been developed for the determination of terazocin in human plasma. Terazocin plus the internal standard, prazocin hydrochloride, were extracted from alkalified plasma with tert-butylmethyl ether, back-extracted into 0.05% phosphoric acid. Fifty ${\mu}l-portions$ of extract were injected onto a octadecylsilane column and eluted with a mixture of acetonitrile, water and triethylamine (30 : 70 : 0.1 v/v, adjusted to pH 5.0 with dilute phosphoric acid) at a flow rate of 1.0 ml/min. The fluorescence intensity of column eluents was monitored at excitation wavelength of 250 nm and emission wavelength of 370 nm. No interference peaks were observed. The practical limit of quantitation was 5 ng/ml for terazocin. The average intraday and interday coefficients of variation were 4.15 and 3.54%, respectively. Also intraday and interday precisions over the range $5{\sim}60\;ng/ml$ were $0.49{\sim}2.92\;and\;0.38{\sim}5.12%$, respectively. The bioequivalence of two terazosin tablets, the $Hytrine^{\circledR}$ (Il Yang Pharmaceutical Co., Ltd.) and the $Teratonin^{\circledR}$ (Sam-A Pharmaceutical Co., Ltd.), was evaluated according to the guideline of Korea Food and Drug Administration (KFDA). Sixteen healthy male volunteers $(24.6{\pm}2.0\;years\;old)$ were divided into two groups and a randomized $2{\times}2$ cross-over study was employed. After one tablet containing 2 mg of terazosin was orally administered, blood was taken at predetermined time intervals and the concentration of terazosin in plasma was determined with a HPLC method using spectrofluorometric detector. AUC was calculated by the linear trapezoidal method. $C_{max}\;and\;T_{max}$ were compiled from the plasma drug concentration-time data. Analysis of variance (ANOVA) was utilized for the statistical analysis of the parameters. The results showed that the differences in $AUC_t,\;C_{max}\;and\;T_{max}$ between the two preparations were 0.21 %, 5.53% and 8.82%, respectively. The powers $(1-{\beta})\;for\;AUC_t,\;C_{max}\;and\;T_{max}$ were >99%, 97.49%, and 33.26%, respectively. Minimum detectable differences $({\Delta},\;%)\;at\;{\alpha}=0.1\;and\;1-{\beta}=0.8$ and the 90% confidence intervals were all less than ${\pm}20%$ except for $T_{max}.\;AUC_t\;and\;C_{max}$ met the criteria of KDFA for bioequivalence, indicating that $Teratonin^{circledR}$ tablets are bioequivalent to $Hytrine^{circledR}$ tablets.

The Effects of Inland Pollution Sources around the Port of Jeokyang and Jangpo after Rainfall Events on Bacteriological Water Quality in the Changseon Area, Korea (강우에 따른 적양항과 장포항 육상오염원이 창선해역에 미치는 세균학적 영향평가)

  • Ha, Kwang Soo;Yoo, Hyun Duk;Shim, Kil Bo;Kim, Ji Hoe;Lee, Tae Seek;Kim, Poong Ho;Lee, Hee Jung;Yu, Hong Sik
    • Korean Journal of Fisheries and Aquatic Sciences
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    • v.46 no.2
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    • pp.160-167
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    • 2013
  • The influences of inland pollution sources nearJeokyang and Jangpoports following rainfall events on the bacteriological water quality and safety of commercial shellfish were investigated in the Changseon area, Korea. Stream flow rates exhibited 1.9- to 5.7-fold increases after rainfall events and then fell to 68~81% of that level after 24 h. The calculated impact area of inland pollution sources was 0.47 $km^2$ in the Jeokyangport area and 0.27 $km^2$ in the Jangpoport area at 24 h following 11 mm of rainfall. When the flow rate of inland pollution increased, the level of male-specific bacteriophage (MSB) decreased, and no MSB could be detected in seawater samples, whereas 30 PFU/100 g was detected in shellfish samples. Fecal coliform levels in seawater and shellfish samples did not exceed their respective tolerance levels (4.5 MPN/100 mL) and 130 MPN/100 g, respectively and thus complied with the standard for approved shellfish growing area. The sanitary conditions of areas adjacent to Jeokyang and Jangpoports under conditions of rainfall below 29 mm met the criteria for approved growing area under the United States National Shellfish Sanitation Program and the EC Regulations.

A Study on the Characterics and Social Activities of Graduates from A School of Public Health in Seoul (보건학 석사과정 이수자들의 제특성 및 사회활동에 관한 조사연구)

  • 김주선;김공현;김병성;박형종
    • Korean Journal of Health Education and Promotion
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    • v.9 no.2
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    • pp.72-88
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    • 1992
  • The purpose of the present study was to identify the charateristics and social activities of graduates from a School of Public Health in Seoul and to provide basic information which might contribute to the improvement of new established Schools of Public Health in Korea. The Subjects were composed of 199 persons who graduated from a School of Public Health in Seoul during the period of 1987 through 1989. The response rate was 59.8% (199 graduates). The survey was conducted from December 1st 1991 to the end of February 1992 with a self-administered questionnaire by mail. Descriptive analysis with Chi-square test was employed for analysis. The major results were as follows : 1. 462% of students were the group aged 24-28 and 76.5% of them were married at the time of entrance to the School. 2. The major motives to come to the School were continuous study in a graduate school(41.2%), and strengthening of job opportunities(35.3%). 3. The major expectation of students were to acquire new professional knowledge(31.9%), to improve present work performance(22.7%) and to become an educator(22.7%). 4. 84.9% of students had some kinds of expectation at the entrance to the School, but only 48.8% of them met their expectations they had had. 5. The most preferred subjects were Health Statistics and Epidemiology in order. 6. 59.7% of students insisted that a professor should advise 4-5 students in maximum for a thesis. 7. Students suggested that the candidate for scholarship should he selected from those who had earned high credits in the previous semester(33.6%), who were low economic status(31.l%) or who were recommended by academic adviser(24.4%). 8. 57.1% of students were positive in utilizing their major subjects studied in their current works. 9. Students expressed that if the School of Public Health is to be further developed full-time professors should be added (37.9%) and excellent students be secured (33.6%). 10. After graduation from the school, some of the respondents changed their job placement, the number of persons working in research institutes increased from 6 to 14 persons, those working in educational institutes from 16 to 35, and Ministry of Health and Social Affairs and its affiliated organization from 10 to 13.

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Incidence and Risk Factors of Contrast-Induced Nephropathy after Bronchial Arteriography or Bronchial Artery Embolization

  • Song, June Seok;Kim, Sa Il;Kim, Woongjun;Park, Dong Won;Kwak, Hyun Jung;Moon, Ji-Yong;Kim, Sang-Heon;Kim, Tae Hyung;Sohn, Jang Won;Shin, Dong Ho;Park, Sung Soo;Yoon, Ho Joo
    • Tuberculosis and Respiratory Diseases
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    • v.74 no.4
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    • pp.163-168
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    • 2013
  • Background: In uncontrolled hemoptysis patient, bronchial arteriography and bronchial artery embolization (BAE) is a important procedure in diagnosis and treatment. The aim of this study is to assess the incidence of contrast-induced nephropathy and the risk factors of contrast-induced nephropathy (CIN) after bronchial arteriography and BAE. Methods: We retrospectively reviewed the medical records of the patients who underwent bronchial arteriography and BAE in two university hospitals from January 2003 to December 2011. CIN was defined as rise of serum creatinine more than 25% of baseline value or 0.5 mg/dL at between 48 hours and 96 hours after bronchial arteriography and BAE. We excluded patients who already had severe renal insufficiency (serum creatinine${\geq}4.0$) or had been receiving dialysis. Results: Of the total 100 screened patients, 88 patients met the enrollment criteria. CIN developed in 7 patients (8.0%). The mean duration between the exposure and development of CIN was $2.35{\pm}0.81$ days. By using multivariate analysis, serum albumin level was found to be significantly associated with the development of CIN (p=0.0219). Conclusion: These findings suggest that the incidence of CIN was higher than expected and patients with hypoalbuminemia should be monitored more carefully to prevent the development of CIN after bronchial arteriography and BAE.

Regulation of Phorbol 12-Myristate 13-Acetate in the Gravitropic Response and Ethylene Production in Primary Roots of Maize (옥수수 뿌리에서 굴중성 반응과 에틸렌 생성에 미치는 Phorbol 12-myristate 13-acetate 조절 작용)

  • Jeong, Yun-Ho;Kim, Jong-Sik;Lee, Kon-Joo;Kim, Soon-Young
    • Journal of Life Science
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    • v.22 no.1
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    • pp.87-91
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    • 2012
  • Phorbol 12-myristate 13-acetate (PMA), a known tumor-promoting phorbol ester, activates the signal transduction enzyme protein kinase C (PKC) in animal cells. We investigated the effect of PMA on the regulation of gravitropism via ethylene production in primary roots of maize. PMA stimulated root growth and the gravitropic response in a concentration-dependent manner at $10^{-6}$ M and $10^{-4}$ M over 8 hrs. These effects were prevented by treatment with staurosporine (STA), a potent inhibitor of PKC. These results support the possibility that the gravitropic response might be regulated through protein kinases that are involved in the signal transduction system. Ethylene is known to play a role in the regulation of root growth and gravitropism. Ethylene production was increased by about 26% and 37% of the control rate in response to $10^{-6}$ M and $10^{-4}$ M PMA, respectively. PMA also stimulated the activity of ACC synthase (ACS), which converts the S-adenosyl-L-methionine (AdoMet) to 1-aminocyclopropane-1-carboxylic acid (ACC) in the ethylene production pathway. These effects on ethylene production were also prevented by STA treatment. These results suggest that the root gravitropic response in maize is regulated through protein kinases via ethylene production.

Nutrition of Range Goats in a Shrubland of Western India

  • Bhatta, Raghavendra;Shinde, A.K.;Sankhyan, S.K.;Verma, D.L.
    • Asian-Australasian Journal of Animal Sciences
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    • v.15 no.12
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    • pp.1719-1724
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    • 2002
  • An investigation was made to evaluate the native range of western India in terms of nutrient supply during different physiological stages in goats. One hundred female and 5 male Kutchi adult goats were grazed on a 35 ha plot of native range. They were maintained on sole grazing. Four experiments, one in a defined physiological stage was carried out. Stage I, when maximum number of females were bred; stage II, when bucks were used for breeding purpose; stage III, 3-months old (weaner) kids were allowed to graze on ranges and stage IV, when the goats were in early stage of lactation. During oestrous period, diet contained 15.2% crude protein (CP), 54.0% neutral detergent fibre (NDF), 31.5% acid detergent fibre (ADF) and 12.6% acid detergent lignin (ADL). Digestibility coefficient of dry matter (DM), CP, NDF and ADF was 0.586,0.531, 0.431 and 0.239, respectively. DM, digestible crude protein (DCP) and metabolizable energy (ME) intakes were $82.7,\;6.71g\;kg^{-1}\;W^{0.75}$ and $0.99MJ\;kg^{-1}\;W^{0.75}$. Diet of buck was constituted by $230g\;kg^{-1}$ DM of grasses and forb and $770g\;kg^{-1}$ DM of tree foliage. CP, NDF, ADF and ADL contents of the diet were 13.6, 57.8, 43.5 and 20.0%, respectively. DM, DCP and ME intakes were $57.9,\;4.13g\;kg^{-1}\;W^{0.75}$ and $0.82MJ\;kg^{-1}\;W^{0.75}$. Digestibility coefficient of CP, NDF and ADF were 0.496, 0.432 and 0.346, respectively. Diet of kids was constituted by Prosopis cineraria ($900g\;kg^{-1}DM$) and Zizyphus nummularia ($100g\;kg^{-1}DM$) leaves. Digestibility of CP, NDF and ADF were 0.456, 0.415 and 0.201, respectively. DM, DCP and ME intakes were $85.8,\;6.44g\;kg^{-1}\;W^{0.75}$ and $1.22MJ\;kg^{-1}\;W^{0.75}$. Lactation phase of goat fell between October-December and tree foliage formed the major portion of the diet. Diet of lactating goat contained only 6.8% CP and 16.5% ADL. Digestibility of DM, CP, NDF and ADF was 0.567, 0.221, 0.307 and 0.233, respectively. DM, DCP and ME intakes were $108.2,\;1.62g\;kg^{-1}\;W^{0.75}$ and $1.50MJ\;kg^{-1}\;W^{0.75}$, respectively. Present study establishes that goats on semiarid range with sufficient number of fodder trees were able to meet the nutrient requirement of ewes during oestrous and bucks during breeding season. However, during lactation and active growth phase, only DM requirement is met. Thus, it is recommended to supplement concentrate mixture to goats grazing on range during lactation and growth phase.