Pharmacokinetics of Anti-tuberculosis Drugs in Gastrectomized Patients

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the effect of gastrectomy on pharmacokinetic profile of first-line anti-tuberculosis drugs in patients with pulmonary tuberculosis (TB).

Detailed Description
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Gastrectomy is a well-known risk factor for TB. Also, there were some reports about malabsorption of anti-TB drugs in the gastrectomized patients. However, pharmacokinetics of recently used first line anti-TB drugs in the gastrectomized patients have not been well evaluated simultaneously. Therefore, the investigators aim to evaluate the effect of gastrectomy on pharmacokinetic profile of first-line anti-TB drugs in patients with pulmonary TB through this study.

Official Title
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Absorption of Anti-tuberculosis Drugs and Its Effect to Treatment Response in Gastrectomized Patients

Conditions
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Tuberculosis, Tuberculosis, Pulmonary, Early Gastric Cancer

Intervention / Treatment
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* Drug: standard first line anti-TB drugs


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age greater than 18 years and less than 80 years pulmonary TB confirmed by microbiologic test such as AFB culture or TB PCR usage of 4 first-line anti-TB drugs (Isoniazid(INH) Rifampin(RFP) Ethambutol(EMB), Pyrazinamide(PZA) = HREZ) Exclusion Criteria: patients with liver disease (bilirubin ≥ 1.5 mg/d or AST ≥ 2 x normal upper limit) or chronic renal failure (Cr ≥ 2.0 mg/d) who cannot use first-line anti-TB drugs patients with AIDS or hypoalbuminemia(albumin < 3.0g/dl)that will influence pharmacokinetics of first line anti-TB drugs patients using other drugs that will influence pharmacokinetics of first line anti-TB drugs during anti-TB treatment (e.g warfarin) patients using anti-cancer or immunosuppressive agents that will influence the response of pulmonary TB to anti-TB drugs discontinuation of first-line anti-TB drugs(HREZ)due to side effect or resistance follow-up loss before completion of anti-TB treatment any condition making the patients undergo gastrectomy during anti-TB treatment in case of Non-gastrectomy group

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Gastrectomy<br>Twenty gastrectomized patients with pulmonary TB, treated with standard first line anti-TB drugs(isoniazid/rifampicin/ethambutol/pyrazinamide), administered daily, orally | Drug: standard first line anti-TB drugs<br>* We will perform pharmacokinetic study in gastrectomy and non-gastrectomy group, to evaluate the effect of gastrectomy on pharmacokinetic profile of first-line anti-TB drugs in patients with TB<br>* Other names: Pharmacokinetics of Anti-tuberculosis Drugs;|
| Non-gastrectomy<br>Twenty non-gastrectomized patients with pulmonary TB, treated with standard first line anti-TB drugs(isoniazid/rifampicin/ethambutol/pyrazinamide), administered daily, orally | Drug: standard first line anti-TB drugs<br>* We will perform pharmacokinetic study in gastrectomy and non-gastrectomy group, to evaluate the effect of gastrectomy on pharmacokinetic profile of first-line anti-TB drugs in patients with TB<br>* Other names: Pharmacokinetics of Anti-tuberculosis Drugs;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The change in the maximum concentration (Cmax) of first-line TB drugs |  | Before and 1, 2, 4, 6 and 8 hours after dosing | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The effects of pharmacokinetics on responses of pulmonary TB to anti-TB drug | Treatment duration can be varied according to several factors such as a first TB episode or not, cavitary TB, and AFB culture(+) after 2month-treatment etc. We will plan 6 or 9 months treatment for each patient according to these factors. During treatment period, we will check chest radiographs and sputum AFB smear/culture with every 2-3month intervals. At 9month after treatment, we will evaluate the effects of pharmacokinetics on responses of pulmonary TB to anti-TB drug by taking account of improvement on chest radiograph and negative conversion and its continuation on sputum smear/culture. | 9month after anti-TB treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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tuberculosis, pharmacokinetics, first-line drugs, gastrectomy