• Title/Summary/Keyword: Effective Dose

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Pharmacokinetic Profiles of Isoniazid and Rifampicin in Korean Tuberculosis Patients (한국인 결핵환자에서 Isoniazid와 Rifampicin의 약동학)

  • Ahn, Seok-Jin;Park, Sang-Joon;Kang, Kyeong-Woo;Suh, Gee-Young;Chung, Man-Pyo;Kim, Ho-Joong;Kwon, O-Jung;Rhee, Chong-H.;Cha, Hee-Soo;Kim, Myoung-Min;Choi, Kyung-Eob
    • Tuberculosis and Respiratory Diseases
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    • v.47 no.4
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    • pp.442-450
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    • 1999
  • Background : Isoniazid(INH) and rifampicin(RFP) are the most effective anti-tuberculosis drugs which make the short-course chemotherapy possible. Although prescribed dosages of INH and RFP in Korea are different from those recommended by American Thoracic Society, there has been few study about pharmacokinetic profiles of INH and RFP in Korean patients who receive INH, RFP, ethambutol(EMB) and pyrazinamide(PZA) simultaneously. Methods : Among the patients with active tuberculosis from Dec. 1997 to July 1998, we selected 17 patients. After an overnight fast, patients were given INH 300mg, RFP 450mg, EMB 800mg and PZA 1500mg daily. Blood samples for the measurement of plasma INH(n=15) and RFP(n=17) level were drawn each at 0, 0.5, 1, 1.5, 2, 4, 6, 8 and 12hrs, and urine was also collected. INH and RFP level in the plasma and the urine were measured by high-performance liquid chromatography(HPLC). Pharmacokinetic parameters such as peak serum concentration(Cmax), time to reach to peak serum concentration(Tmax), half-life, elimination rate constant(Ke), total body clearance(CLtot), nonrenal clearance(CLnr), and renal clearance(CLr) were calculated. Results : 1) Pharmacokinetic parameters of INH were as follows: Cmax; $7.63{\pm}3.20{\mu}g/ml$, Tmax; $0.73{\pm}0.22hr$, half-life; $2.12{\pm}0.84hrs$, Ke; $0.83{\pm}0.15hrs^{-1}$, CLtot; $17.54{\pm}8.89L/hr$, CLnr; $14.74{\pm}8.35L/hr$, CLr; $2.79{\pm}1.31L/hr$. 2) Pharmacokinetic parameters of RFP were as follows: Cmax; $8.93{\pm}3.98{\mu}g/ml$, Tmax; $1.76{\pm}1.13hrs$, half-life; $2.27{\pm}0.54hrs$, Ke; $0.32{\pm}0.08hrs^{-1}$, CLtot; $14.63{\pm}6.60L/hr$, CLr; $1.04{\pm}0.55L/hr$, CLnr; $13.59{\pm}6.21L/hr$. 3) While the correlation between body weight and Cmax of INH was not statistically significant (r=-0.514, p value>0.05), Cmax of RFP was significantly affected by body weight of the patients(r=-0.662, p value<0.01). Conclusion : In Korean patients with tuberculosis, 300mg of INH will be sufficient to reach the ideal peak blood level even in the patients over 50kg of body weight However, 450mg of RFP will not be the adequate dose in the patients who weigh over 50~60kg.

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A Study for Improvement of Erythropoietin Responsiveness in Hemodialysis Patients (혈액 투석 환자에서 조혈 호르몬 치료 효과 향상에 대한 연구)

  • Park, Jong-Won;Do, Jun-Yeung;Yoon, Kyung-Woo
    • Journal of Yeungnam Medical Science
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    • v.18 no.2
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    • pp.226-238
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    • 2001
  • Background: Anemia in chronic renal failure plays an important role in increasing morbidity of dialysis patients. The causes of the anemia are multifactorial. With using of erythropoietin(EPO) most of uremia-induced anemia can be overcome. However, about 10% of renal failure patients shows EPO-resistant anemia. Hyporesponsiveness to EPO has been related to many factors: iron deficiency, aluminum intoxication, inflammations, malignancies and secondary hyperparathyroidism. So I evaluated the improvement of EPO responsiveness after correction of above several factors. Materials and Methods: Seventy-two patients on hemodialysis over 6 months were treated with intravenous ascorbic acid(IVAA, 300 mg t.i.w. for 12 weeks), After administration of IVAA for 12 weeks, patients were classified into several groups according to iron status, serum aluminum levels and i-PTH levels. Indivisualized treatments were performed: increased iron supplement for absolute iron deficiency, active vitamin D3 for secondary hyperparathyroidism and desferrioxamine(DFO, 5 mg/kg t.i.w.) for aluminum intoxication or hyperferritinemia. Results: 1) Result of IVAA therapy for 12 weeks on all patients(n=72). Hemoglobin levels at 2, 4, 6 week were significantly elevated compared to baseline, but those of hemoglobin at 8, 10, 12 week were not significantly different. 2) Result of IVAA therapy for 20 weeks on patients with 100 ${\mu}g/l$ ${\leq}$ ferritin < 500 ${\mu}g/l$ and transferrin saturation(Tsat) below 30%(n=30). After treatment of IV AA for 12 weeks, patients were evaluated the response of therapy according to iron status. Patients with 100 ${\mu}g/l$ ${\leq}$ ferritin < 500 ${\mu}g/l$ and Tsat below 30% showed the most effective response. These patients were treated further for 8 weeks. Hemoglobin levels at 2, 4 week were significantly increased compared to baseline with significantly reduced doses of EPO at 2, 4, 6, 10, 12, 16, 20 week. Concomitantly significantly improvement of Tsat at 2, 6, 16, 20 week compared to baseline were identified. 3) Result of IVAA therapy for 12 weeks followed by DFO therapy for 8 weeks on patients with serum aluminum above 4 ${\mu}g/l$(n=12) Hemoglobin levels were not significantly increased during IVAA therapy for 12 weeks but dosages of EPO were significantly decreased at 2, 4, 6, 8 week during DFO therapy compared to pre-treatment status. Conclusion: IVAA can be helpful for the treatment of the anemia caused by functional iron deficiency and can reduce the dosage of EPO for anemia correction. And administration of low dose DFO, in cases of increased serum aluminum level, can reduce the requirement of EPO.

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