• Tuberculosis and Respiratory Diseases
• /
• v.44 no.3
• /
• pp.479-492
• /
• 1997

Background : Isoniazid(INH) and rifampicin(RFP) are potent antituberculous drugs which have made tuberculous disease become decreasing. In Korea, prescribed doses of INH and RFP have been different from those recommended by American Thoracic Society. In fact they were determined by clinical experience rather than by scientific basis. Even there has been. few reports about pharmacokintic parameters of INH and RFP in healthy Koreans. Method : Oral pharmacokinetics of INH were studied in 22 healthy native Koreans after administration of 300 mg and 400mg of INH to each same person successively at least 2 weeks apart. After an overnight fast, subjects received medication and blood samples were drawn at scheduled times over a 24-hour period. Urine collection was also done for 24 hours. Pharmacokinetics of RFP were studied in 20 subjects in a same fashion with 450mg and 600mg of RFP. Plasma and urinary concentrations of INH and RFP were determined by high-performance liquid chromatography(HPLC). Results : Time to reach peak serum concentration (Tmax) of INH was $1.05{\pm}0.34\;hrs$ at 300mg dose and $0.98{\pm}0.59\;hrs$ at 400mg dose. Half-life was $2.49{\pm}0.88\;hrs$ and $2.80{\pm}0.75\;hrs$, respectively. They were not different significantly(p > 0.05). Peak serum concentration(Cmax) after administration of 400mg of INH was $7.14{\pm}1.95mcg/mL$ which was significantly higher than Cmax ($4.37{\pm}1.28mcg/mL$) by 300mg of INH(p < 0.01). Total clearance(CLtot) of INH at 300mg dose was $26.76{\pm}11.80mL/hr$. At 400mg dose it was $21.09{\pm}8.31mL/hr$ which was significantly lower(p < 0.01) than by 300mg dose. While renal clearance(CLr) was not different among two groups, nonrenal clearance(CLnr) at 400mg dose ($18.18{\pm}8.36mL/hr$) was significantly lower than CLnr ($23.71{\pm}11.52mL/hr$) by 300mg dose(p < 0.01). Tmax of RFP was $1.11{\pm}0.41\;hrs$ at 450mg dose and $1.15{\pm}0.43\;hrs$ at 600mg dose. Half-life was $4.20{\pm}0.73\;hrs$ and $4.95{\pm}2.25\;hrs$, respectively. They were not different significantly(p > 0.05). Cmax after administration of 600mg of RFP was $13.61{\pm}3.43mcg/mL$ which was significantly higher than Cmax($10.12{\pm}2.25mcg/mL$) by 450mg of RFP(p < 0.01). CLtot of RFP at 450mg dose was $7.60{\pm}1.34mL/hr$. At 600mg dose it was $7.05{\pm}1.20mL/hr$ which was significantly lower(p < 0.05) than by 450mg dose. While CLr was not different among two groups, CLnr at 600 mg dose($5.36{\pm}1.20mL/hr$) was significantly lower than CLnr($6.19{\pm}1.56mL/hr$) by 450mg dose(p < 0.01). Conclusion : Considering Cmax and CLnr, 300mg, of INH and 450mg RFP might be sufficient doses for the treatment of tuberculosis in Koreans. But it remains to be clarified in the patients with tuberculosis.

• Tuberculosis and Respiratory Diseases
• /
• v.44 no.6
• /
• pp.1308-1317
• /
• 1997

Background : Pulmonary aspergillomas usually arise from colonization and proliferation of Aspergillus in preexisting cavitary lung disease of any cause. About 15% of patients with tuberculous pulmonary cavities were found to have aspergilloma. We analyzed the clinical features and course of 91 patients with pulmonary aspergilloma. Method : During the ten-year period from June 1986 to May 1996, 91 patients whose condition was diagnosed as pulmonary aspergilloma at 4 university hospitals in Taegu city were reviewed. All patients fulfilled one of the following criteria : 1) histologic evidence of aspergilloma within abnormal air space in tissue sections, or 2) a positive Aspergillus serum precipitin test with the radiologic finding of a fungus ball. The histological diagno-sis was established in 81 patients(89.0%) and clinical diagnosis in 10 patients(11.0%). Results : 1) The age range was 22 to 65 years, with an average of 45 years. A male and female ratio was 1.7 : 1 (57 men and 34 women). 2) Hemoptysis was far the most frequent symptom(89%), followed by cough, dyspnea, weakness, weight loss, fever, chest pain. 3) In all but 14 cases(15.4%) there had been associated conditions. Pulmonary tuberculosis was far the most frequent underlying condition found(74.7%), followed by bronchiectasis (6.6%), cavitary neoplasm(2.2%), pulmonary sequestration(1.1%). 4) The involved area was usually in the upper lobes; the right upper lobe was involved in 39(42.9%), the left upper lobe in 31(34.1%), the left lower lobe in 13(14.3%), the right lower lobe in 7(7.7%), and the right middle lobe in 1(1.1%). 5) On standard chest roent geno gram the classic "bell-like" image of a fungus ball was found in 62.6% of the subjects. On CT scan, 88.1% of the subjects in which they were done. 6) The surgical therapy was undertaken in 76 patients, and medical therapy in 15 patients, including 4 patients with intracavitary instillation of amphotericin B. 7) The surgical modality was lobectomy in 55 patients(72.4%), segmentectomy in 16 patients(21.1%), pneumonectomy in 4 patients(5.3%), wedge resection in 1 patient(1.3%). The mortality rate was 3.9% (3 patients) ; 2 patients died of sepsis and 1 died of hemoptysis. The postoperative complications were encountered in 6 patients (7.9%), including each one patient with respiratory failure, bleeding, bronchopleural fistula, empyema, and vocal cord paralysis. 8) In the follow-up cases, each 2 patients of 71 patients with surgical treatment and 10 patients with medical treatment had recurrent hemoptysis. Conclusion : During follow-up of the chronic pulmonary disease with abnormal air space, if the standard chest roentgenograms are insufficient to detect a fungus ball, computed tomographic scan and serum precipitin test are likely to aid the diagnosis of patients with suspected pulmonary aspergilloma. A reasonable recommendation for management of a patient with aspergilloma would be to reserve surgical resection for those patients who have had severe, recurrent hemoptysis. And a well controlled cooperative study to the medical treatment such as intracavitary antifungal therapy is further needed.