Salivary Therapeutic Drug Monitoring of Anti-Tuberculosis Drugs

Tuberculosis Clinical Trial

Official title:

An Observational Study of Salivary Versus Blood Concentrations of Various Anti-Tuberculosis Drugs in Tuberculosis Patients

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03080012
• Other study ID #: SALIV-01
• Status: Completed
• Start date: March 7, 2017
• Est. completion date: May 2, 2018

Study information

• Verified date: November 2018
• Source: University Medical Center Groningen
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 24
• Est. completion date: May 2, 2018
• Est. primary completion date: May 2, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• 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

Exclusion Criteria:

• Patient with severe problems in the oral cavity, making saliva sampling painful

Related Conditions & MeSH terms

• Tuberculosis

Intervention

Other:
• Saliva sampling
Stimulated saliva samples are taken using cotton rolls.
• Plasma/serum sampling
Simultaneously with saliva sampling.

Locations

Country	Name	City	State
Netherlands	University Medical Center Groningen (UMCG) Beatrixoord	Haren	Groningen

Sponsors (1)

Lead Sponsor	Collaborator
University Medical Center Groningen

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Saliva-plasma ratio or saliva-serum ratio	Ratio of salivary versus blood concentration calculated with salivary and plasma/serum values of area under the time-concentration curve (AUC)	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
Secondary	Salivary drug concentration	Measured drug concentration in saliva	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
Secondary	Plasma/serum drug concentration	Measured drug concentration in plasma or 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
Secondary	Area under the time-concentration curve (AUC) in saliva and plasma/serum	Calculated in both saliva and plasma/serum using the drug concentration at all time points.	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
Secondary	Peak concentration (Cmax) in saliva and plasma/serum	Calculated in both saliva and plasma/serum using the drug concentration at all time points.	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
Secondary	Time of peak concentration (Tmax) in saliva and plasma/serum	Calculated in both saliva and plasma/serum using the drug concentration at all time points.	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
Secondary	Trough concentration (Cmin) in saliva and plasma/serum	Calculated in both saliva and plasma/serum using the drug concentration at all time points.	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
Secondary	Clearance (Cl) in saliva and plasma/serum	Calculated in both saliva and plasma/serum using the drug concentration at all time points.	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
Secondary	Half-life (t1/2) in saliva and plasma/serum	Calculated in both saliva and plasma/serum using the drug concentration at all time points.	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
Secondary	Elimination constant (Kel) in saliva and plasma/serum	Calculated in both saliva and plasma/serum using the drug concentration at all time points.	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