Background: Rifampicin, isoniazid, and pyrazinamide are oral essential anti-tuberculosis drugs on single or combined preparations. Worldwide research has shown that the plasma concentration of anti-tuberculosis drugs with daily therapeutic doses were seen significant lower than permitted in tuberculosis patients, especially for rifampicin and isoniazid. Objective: To investigate plasma concentration of rifampicin, isoniazid, and pyrazinamide in pulmonary tuberculosis and pleural tuberculosis patients. Methods: Determine plasma concentration of rifampicin, isoniazid, and pyrazinamide at 2 hours after administration in 168 tuberculosis patients by the HPLC method. Identify prevalence of low plasma concentrations of anti-tuberculosis drugs. Results: There was a wide range of plasma concentration of rifampicin, isoniazid, and pyrazinamide in the tuberculosis patients. The mean plasma concentration of rifampicin was 6.13 \xb1 4.66 microgram/ml, of isoniazid was 2.99 \xb1 1.94 microgram/ml, pyrazinamide was 38.98 \xb1 18.39 microgram/ml. There was no significant differences in the plasma concentration of rifampicin, isoniazid, and pyrazinamide in groups of pulmonary tuberculosis and pleural tuberculosis patients. Percentage of patients with plasma concentration below therapeutic concentration was 76.83% of rifampicin, 51.85% of isoniazid, 10.13% of pyrazinamide. There were 12.03% of patients who had pyrazinamide concentration higher than the therapeutic range. Conclusions: There was a wide range of plasma concentration in rifampicin, isoniazid, and pyrazinamide of tuberculosis patients. Low plasma concentration of rifampicin and isoniazid are common. It may be necessary to optimize the drug dose by therapeutic drug monitoring, especially in patients with an inadequate clinical response to chemotherapy.
tuberculosis ; rifampicin ; isoniazid ; pyrazinamide

A marked low concentration of serum uric acid(0.7-1.2mg/dl) was detected in a 14-year-old boy with recurrent episodes of gross hematuria. The hypouricemia accompanied with a markedly increased urinary clearance of uric acid (32.6-56.0ml/min), which was only minimally changed after both the administration of pyrazinamide, and inhibitor of the renal tubular secretion of uric acid, and the administration of probenecid, and inhibitor of the renal tubular reabsorption of uric acid. Other renal tubular functions were normal. There were no other family members with hypouricemia. Thies is the first case report of isolated renal hypouricemia due to presecretory reabsorption defect of uric acid in the renal proximal tubule in Korea. And renal hypouricemia should be included in the diagnosis of hematuria.
Adolescent ; Diagnosis ; Hematuria* ; Humans ; Korea ; Male ; Probenecid ; Pyrazinamide ; Uric Acid

Drug-induced thrombocytopenia and purpura have boon developed by many various agents. Rifampin and Pyrazinamide have been known as bactericidal antituberculous drugs, but, the above side effects have been a problem. Especially, hematologic side effects art fatal to patients occasionally. Rifampin-induced thrombocytopenia and purpura have been well known, also, pyrazinamide-induced thrombocytopenia have been reported. A new quilonone agent Ciprofloxacin, has been commonly used in clinics now, but it's side effects are not known well. So, we report a case of a 23-year-old female with thrombocytopenia and purpura after taking Rifampin, Pyrazinamide, and Ciprofloxacin as antituberculous agents.
Ciprofloxacin* ; Female ; Humans ; Purpura* ; Pyrazinamide* ; Rifampin ; Thrombocytopenia* ; Young Adult

The study was conducted to compare bioavailability of rifampicin at the same doses with and without isoniazid and pyrazinamide in the standard separate tablets in 12 healthy volunteers. Bioavailability of rifampicin was estimated by plasma concentration of rifampicin from 0h to 24h after administration. Plasma rifampicin concentration was determined by HPLC method. The results revealed that Cmax and AUC for rifampicin was reduced (31.24% and 25.95%, respectively) when rifampicin - isoniazid - pyrazinamide was administeredat the same time. It was concluded that bioavailability of rifampicin was affected by presence of isoniazid and pyrazinamide.
Tuberculosis ; Tuberculosis, Multidrug-Resistant ; Pyrazinamide ; Rifampin ; Biological ; Availability

A HPLC method has been used to quantify plasma rifampicin and isoniazid and pyrazinamide simultaneously. Extraction of rifampicin in plasma samples was done as follows: mix 1ml of plasma containing rifampicin and 1.5 ml acetonitril on a vortex mixer for 1 minute prior to centrifugation at 3500 rpm for 30 minutes. The organic layer was filtered through 0.45m filter membrane and then 30l of this solution was injected into the HPLC system. The chromatographic conditions were as follows: in stationary phase: column: Apollo Alltech RP18 (250 x 4.6 mm; 5 m); in mobile phase: methanol - phosphate buffet solution containing 0.02M potassium dihydrogen phosphate adjusted to pH 4.5 by adding phosphoric acid (65: 35); Flow rate: 1.0 ml/min and UV detector: 254 nm
Chromatography, High Pressure Liquid ; lasma ; Pyrazinamide ; Isoniazid ; Rifampin

INTRODUCTION: Development of drug resistance is one of the most important barriers in achieving global control of tuberculosis (TB). Continuous surveillance, such as observation of susceptibility and resistance patterns to anti-TB drugs, together with nationwide programs aimed at TB case identification, treatment and control, physician and patient education, is a valuable tool in the goal towards reducing TB prevalence and mortality.
OBJECTIVE: It is the aim of this study to determine the prevalence rate and resistance pattern of  first line anti-tuberculosis drugs in a tertiary hospital in Manila, Philippines
MATERIALS AND METHODS: Records of specimens submitted for Mycobacterium tuberculosis (MTB) culture and sensitivity, using BACTEC TM MGIT TM 960 SIRE Kit and PZA Kit, at the Section of Clinical Pathology, University of Santo Tomas Hospital, were reviewed. Isolates cultured for MTB were subjected to sensitivity studies to rifampicin (R),isoniazid (H), ethambutol (E), pyrazinamide (Z) and streptomycin (S).
RESULTS: A total of 546 specimens were cultured for MTB and sent for sensitivity studies. Majority of the specimens were from pulmonary sources (77%). Overall resistance rate was 52.38% (n=286). One-drug resistance was 23.26% (n= 127; highest with R followed by H); two-drug resistance was 15.38% (n=84; highest with H-R); three-drug resistance was 8.61% (n=47; highest with H-R-E and H-R-S); four-drug resistance was 4.58% (n=25; highest with H-R-E-S) and five-drug resistance (H-R-E-S-Z) rate was 0.55% (n=3). 
CONCLUSION: The University of Santo Tomas Hospital, as a referral facility, is encountering an increasing number of drug-resistant tuberculosis from 2003 to 2013.

Human ; Male ; Female ; Aged ; Middle Aged ; Adult ; Ethambutol ; Mycobacterium Tuberculosis ; Isoniazid, Pyrazinamide, Rifampin Drug Combination ; Pyrazinamide ; Isoniazid ; Rifampin ; Streptomycin ; Pathology, Clinical ; Tuberculosis

Background: Many clinicians have experienced the difficulty of decision on termination of antituberculosis chemotherapy after the 6th month due to relapse of disease. There is still controversy in the effect of 2S(K)HRZ/4HRZ 6-month short course chemotherapy including pyrazinamide for 6 months in patients with pulmonary tuberculosis. And there is no long term follow-up study of 6-month short course chemotherapy for pulmonary tuberculosis in korea. So we had performed the study to find the result of 6-month antituberculosis chemotherapy for 4 years. Method: We studied prospectively the effect of 2S(K)HRZ/4HRZ in one hundred-fifty patients with pulmonary tuberculosis and followed up fifty-nine patients for more than 1 year to 4 years after the completion of 6-month short course therapy. Results: 1) Out of one hundred-fifty patients, seventy-two patients(48%) completed the prescribed 6-month chemotherapy. Sixty-eight patients(45.3%) have experienced premature discontinuation and the most common cause of premature discontinuation was drop-out against advice(thirty-six patients, 24%). Ten patients(6.7%) were treated beyond the 6 months mainly due to irregular treatment. 2) Fifty-nine patients(81.9%) among seventy-two patients with completed treatment have been followed up for more than 1 year and 32 patients(44.4%) for more than 4 years. There was three relapse patients of whom two patients have experienced relapse of pulmonary tuberculosis within 1 year after the termination of chemotherapy. 3) Among one hundred-thirty-four patients who have been assessible for more than two months of chemotherapy, including the patients who experienced within 2 months, there were eighty-two patients(61.2%) who have experienced adverse reactions and the treament regimen was changed only in thirteen patients(9.7%). The most frequent cause of adverse reactions was arthralgia and/or hyperuricemia, which had occurred in 33 patients(24.6%). Conclusion: In a university hospital in Korea, 6-month short course chemotherapy of 2S(K)HRZ/4HRZ had unnegligible relapses and premature discontinuation. Therefore, change of the regimen might be carefully considered by drug susceptibility results. Close monitoring of patients, retrial of sputum exam and radiologic evaluation during treatment might be required in the endemic area of drug resistant strains like in Korea. Further study about the effect of 6-month short course chemotherapy including pyrazinamide for 6-month might be needed.
Arthralgia ; Drug Therapy ; Follow-Up Studies* ; Humans ; Hyperuricemia ; Korea ; Prospective Studies ; Pyrazinamide ; Recurrence ; Sputum ; Tuberculosis, Pulmonary*

Superior vena cava syndrome(SVCS) is most often encountered in patients with malignancies. Tuberculosis is nowadays an uncommon cause of SVCS. We report the case of a patient who presented with respiratory symptoms accompanied by SVCS due to tuberculous lymphadenitis. Treatment was instituted with isoniazid, rifampicin, pyrazinamide and ethambutol, and all symptoms disappeared. To our knowledge, no case of SVCS provoked by tuberculous lymphadenitis has been described previously in Korea.
Ethambutol ; Humans ; Isoniazid ; Korea ; Lymphadenitis ; Pyrazinamide ; Rifampin ; Tuberculosis ; Tuberculosis, Lymph Node* ; Vena Cava, Superior

We encountered a case of renal hypouricemia and absorptive hypercalciuria. Although renal hypouricemia is asymptomatic as usual, it is rarely complicated with acute renal failure and urolithiasis. A 43-year-old man had hypouricemia (serum uric acid, 0.6-1.0mg/dl) with an increased renal uric acid clearance (69.4ml/min), hypercalciuria (367.2mg/day). In present case, there was no response of uric acid excretion to either pyrazinamide or probenecid and hypercalciuria disappeared after calcium restriction diet. These results suggest that the present case had the defect of both pre-and postsecretory reabsorption of uric acid and absorptive hypercalciuria.
Acute Kidney Injury ; Adult ; Calcium ; Diet ; Humans ; Hypercalciuria* ; Probenecid ; Pyrazinamide ; Uric Acid ; Urolithiasis

BACKGROUND: Joint symptoms frequently occur in the course of antituberculous chemotherapy and tend to be ignored and overlooked, but in some cases, they are often very troublesome in obstructing ordinary life. Joint symptoms that develop during antituberculous chemotherapy need to be understood, but there are few materials describing them systematically. METHOD: This study enrolled 33 patients with tuberculosis treated with first line antituberculous agents for more than 6months. In the course of treatment, joint symptoms not associated with specific cause, such as pre-existing joint disease or trauma, were investigated and compared with those of the asymptomatic group, We confirmed the incidence of joint symptoms and factors associated with them. RESULTS: Nineteen of 33 patients (58%) had joint symptoms. Joint symptoms developed 1.9±1.4 months after the beginning of chemotherapy and lasted for 3.6±2.5 months. IN 18 of 19 symptomatic patients, multiple joints were involved : shoulder(10 patients, 53%), knee(10,53%), finger(6,32%). Joint symptoms were expressed as pain(19 patients, 100%), stiffness(7,37%) and/or swelling (3,16%). Fourteen patients (74%) took analgesics to relieve their symptoms and in 2 patients, antituberculous agents were discontinued because of the severity of their symptoms. The symptoms seem to be caused by agents other than pyrazinamide, but it was very difficult to identify the definite causative agent. In age, sex, underlying disease and serum uric acid level, no significant differences were noted between the two groups. CONCLUSIONS: Although joint symptoms are common during antituberculous chemotherapy, their development is difficult to predict. Because some joint symptoms can become very bothersome, the physician should pay close attention to these symptoms.
Analgesics ; Arthralgia ; Drug Therapy* ; Humans ; Incidence ; Joint Diseases ; Joints* ; Pyrazinamide ; Tuberculosis ; Uric Acid