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African Journal of Pharmacy and Pharmacology Vol. 5(17), pp. 2035-2041, 8 November, 2011
Available online at http://www.academicjournals.org/AJPP
DOI: 10.5897/AJPP11.511
ISSN 1996-0816 © 2011 Academic Journals
Full Length Research Paper
Therapeutic monitoring of isoniazid, rifampicin,
ethambutol and pyrazinamide serum levels in the
treatment of active pulmonary tuberculosis and
determinants of their serum concentrations
Servet Kayhan 1,2 * and Alper Akgüneş 1,3
1 Chest Diseases and Thoracic Surgery Hospital, Samsun, Turkey.
2 Department of Pulmonary Disease And Tuberculosis, Ministry of Health, Chest Diseases and Thoracic Surgery
Hospital, Samsun, Turkey.
3 Department of Microbiology, Ministry of Health, Chest Diseases and Thoracic Surgery Hospital, Samsun, Turkey.
Accepted 12 October, 2011
Inadequate serum levels of antimycobacterial drugs have been associated with treatment failure,
relapse and acquired drug resistance as well as high concentrations of these drugs may cause
intolerance and toxic effects. We objected in this study to determine serum concentrations of antituberculosis
drugs and to know the determinants of their concentrations. Venous blood samples was
obtained 2 and 6 h after drug ingestion, and serum levels of drugs were analysed using high
performance liquid chromatography. Among 49 enrolled active pulmonary tuberculosis patients, the
prevalances of a low concentration of isoniazid, rifampicin, ethambutol and pyrazinamide were 28.6,
75.5, 18.4 and 20.4%, respectively. 2 h ısoniazid (INH) concentration was found to be associated with
sex (p = 0.005), correlated with body mass index (r = -0.390) and associated with drug dose (mg/kg) (p =
0.000). By Independent samples t-test analysis, low 2 h rifampicin concentration was found to be
associated with sex (p = 0.000) and smoking cigarette (p = 0.004). In conclusion, the results of this
study have shown that, low 2 h serum INH and rifampicin (RIF) concentration are common and It may be
necessary to optimise drug doses by therapeutic drug monitoring.
Key words: Therapeutic drug monitoring, tuberculosis, isoniazid, rifampicin, ethambutol, pyrazinamide.
INTRODUCTION
The World Health Organisation estimated the global
burden of tuberculosis(TB) in 2010 as around 14 million
prevalance and 2.38 million deaths from this curable
infectious disease (WHO, 2010). Despite directly
observed therapy (DOT) in TB control programs,
treatment failure, relapse, acquired drug resistance,
increasing in number of multidrug resistant cases and
drug toxicities remain ongoing complications in some TB
patients. Serum concentrations of anti-tuberculosis drugs
have been associated with many factors such as
malabsorption, smoking status, comorbidity of diabetes
mellitus and HIV, alcohol consumption,
hypoalbuminaemia, calculated creatinine clearance by
*Corresponding author. E-mail: servet-kayhan@hotmail.com.tr.
Cockcroft-Gault equation for EMB (Cockroft and Gault,
1976), liver and kidney dysfunctions, low dose per
kilogram of body weight, changes in drug formulation,
age and gender (Um et al., 2007; Mcllleron et al., 2006;
Narita et al., 2001). Low serum concentrations of antituberculosis
drugs has been reported as a reason for
treatment failure, relapse and acquired drug resistance in
previous studies (Heysell et al., 2010; Mehta et al., 2001).
Low serum levels can be a consequence of
malabsorption, inaccurate dosing, altered metabolism, or
drug interactions, but in most instances low serum levels
can be readily corrected with dose adjustment. TDM is
currently recommended in TB treatment guidelines as
optional (Peloquin, 2002; Blumberg et al., 2003).
Although certain patients infected with HIV and thus
prone to malabsorption, are at higher risk for low drug
levels, studies of TDM that included patients responding