Clinical pharmacology and therapeutic drug monitoring of first-line anti-tuberculosis drugs
| PhD ceremony: | dr. M.G.G. (Marieke) Sturkenboom |
| When: | March 23, 2016 |
| Start: | 11:00 |
| Supervisors: | prof. dr. J.G.W. (Jos) Kosterink, prof. dr. T.S. (Tjip) van der Werf, prof. dr. D.R.A. Uges |
| Co-supervisor: | dr. J.W.C. (Jan-Willem) Alffenaar |
| Where: | Academy building RUG / Student Information & Administration |
| Faculty: | Medical Sciences / UMCG |
Tuberculosis (TB), which is caused by Mycobacterium tuberculosis, is one of the infectious diseases with the highest morbidity and mortality worldwide. In 2014, an estimated 9.6 million people developed TB and 1.5 million people died of the disease. Drug-susceptible TB is treated for two months with the first-line anti-TB drugs, isoniazid, rifampicin, pyrazinamide and ethambutol, followed by isoniazid and rifampicin for another four months. Effective treatment with these drugs is challenged by the emergence of drug resistance, toxicity, relapse and non-response.
In this thesis, we explored individualized treatment approaches with conceivably more precision. We describe factors to consider when a patient is dosed with first-line anti-TB drugs and propose methods to optimize treatment in drug-susceptible TB.
We performed a literature review on the role of an analysis technique, which is used for the quantification of anti-infective drugs. We developed a sensitive and fast analysis method for the quantification of isoniazid, pyrazinamide and ethambutol in human blood. Furthermore, we described an inter-laboratory quality control programme for measurement of the four first-line anti-TB drugs and two second-line anti-TB drugs, moxifloxacin and linezolid. Second-line anti-TB drugs can be used if the Mycobacterium has developed resistance against one of more of the first-line anti-TB drugs. We developed a method that facilitates prediction of exposure of rifampicin in TB patients. Lastly, we investigated which patient variables influence exposure of isoniazid and rifampicin. We studied the influence of concomitant food intake on the exposure of isoniazid, rifampicin, pyrazinamide and ethambutol.