An Observational Study of Salivary Versus Blood Concentrations of Various Anti-Tuberculosis Drugs in Tuberculosis Patients
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 24
- 试验地点
- 1
- 主要终点
- Saliva-plasma ratio or saliva-serum ratio
研究概览
简要总结
In tuberculosis patients, salivary concentrations will be compared to plasma/serum concentrations of several anti-tuberculosis drugs. If salivary concentrations correctly represent blood concentrations, this non-invasive sampling of saliva could be used for TDM of the tested drugs.
详细描述
TDM (Therapeutic Drug Monitoring) with blood samples is already part of the treatment of some tuberculosis (TB) patients to reduce development of drug resistance and toxic drug concentrations. Performing TDM with saliva instead of plasma or serum could reduce the burden of blood sampling. This study examines if this non-invasive sampling of saliva could be used for TDM of several anti-TB drugs.
The study is an observational cohort study with adult tuberculosis patients as subjects. The drugs that are studied are isoniazid, rifampicin, ethambutol, pyrazinamide, moxifloxacin, amikacin, kanamycin, capreomycin, ethionamide, prothionamide, cycloserine, terizidone, linezolid, clofazimine, bedaquiline, delamanid, p-aminosalicylic acid (PAS), imipenem-cilastatin, meropenem, ertapenem, amoxicillin-clavulanate and thioacetazone.
Saliva samples will be taken simultaneously with blood samples for standard TDM. Serum/plasma and saliva drug concentrations will be determined with a validated LC-MS/MS (liquid chromatography-tandem mass spectrometry) method. The correlation and linearity between saliva and plasma/serum concentrations will be tested. The saliva-plasma or serum ratio based on area under the time-concentration curve (AUC) is calculated for the investigated anti-TB drugs. Also pharmacokinetic parameters in serum/plasma and saliva will be calculated and compared to provide a complete image of pharmacokinetics of the anti-TB drugs in saliva.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Tuberculosis is confirmed by culture or molecular test
- •Patient is treated with anti-tuberculosis drugs included in study
- •Patient receives Therapeutic Drug Monitoring (TDM) in routine care
- •Patient signed informed consent
排除标准
- •Patient with severe problems in the oral cavity, making saliva sampling painful
结局指标
主要结局
Saliva-plasma ratio or saliva-serum ratio
时间窗: 0, 0.5, 1, 2, 3, 4, 7 hours post-dose for isoniazid, rifampicin, ethambutol and pyrazinamide or 0, 1, 2, 3, 4, 8 hours post-dose for all other drugs
Ratio of salivary versus blood concentration calculated with salivary and plasma/serum values of area under the time-concentration curve (AUC)
次要结局
- Salivary drug concentration(0, 0.5, 1, 2, 3, 4, 7 hours post-dose for isoniazid, rifampicin, ethambutol and pyrazinamide or 0, 1, 2, 3, 4, 8 hours post-dose for all other drugs)
- Plasma/serum drug concentration(0, 0.5, 1, 2, 3, 4, 7 hours post-dose for isoniazid, rifampicin, ethambutol and pyrazinamide or 0, 1, 2, 3, 4, 8 hours post-dose for all other drugs)
- Area under the time-concentration curve (AUC) in saliva and plasma/serum(0, 0.5, 1, 2, 3, 4, 7 hours post-dose for isoniazid, rifampicin, ethambutol and pyrazinamide or 0, 1, 2, 3, 4, 8 hours post-dose for all other drugs)
- Trough concentration (Cmin) in saliva and plasma/serum(0, 0.5, 1, 2, 3, 4, 7 hours post-dose for isoniazid, rifampicin, ethambutol and pyrazinamide or 0, 1, 2, 3, 4, 8 hours post-dose for all other drugs)
- Elimination constant (Kel) in saliva and plasma/serum(0, 0.5, 1, 2, 3, 4, 7 hours post-dose for isoniazid, rifampicin, ethambutol and pyrazinamide or 0, 1, 2, 3, 4, 8 hours post-dose for all other drugs)
- Peak concentration (Cmax) in saliva and plasma/serum(0, 0.5, 1, 2, 3, 4, 7 hours post-dose for isoniazid, rifampicin, ethambutol and pyrazinamide or 0, 1, 2, 3, 4, 8 hours post-dose for all other drugs)
- Half-life (t1/2) in saliva and plasma/serum(0, 0.5, 1, 2, 3, 4, 7 hours post-dose for isoniazid, rifampicin, ethambutol and pyrazinamide or 0, 1, 2, 3, 4, 8 hours post-dose for all other drugs)
- Time of peak concentration (Tmax) in saliva and plasma/serum(0, 0.5, 1, 2, 3, 4, 7 hours post-dose for isoniazid, rifampicin, ethambutol and pyrazinamide or 0, 1, 2, 3, 4, 8 hours post-dose for all other drugs)
- Clearance (Cl) in saliva and plasma/serum(0, 0.5, 1, 2, 3, 4, 7 hours post-dose for isoniazid, rifampicin, ethambutol and pyrazinamide or 0, 1, 2, 3, 4, 8 hours post-dose for all other drugs)
研究者
Jan-Willem C Alffenaar
PhD, PharmD
University Medical Center Groningen