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2040 Afr. J. Pharm. Pharmacol.
Figure 5. Pyrazinamide(PZA) serum levels of each patients < 20 µg/ml 20.4% (10/49) n = 49.
to previous studies, serum concentrations of INH are
related to many factors, that is, age, sex, a prior history of
TB, serum haemoglobin levels, laxative use, HIV
infection, fixed-drug combinations formulation, fasting
and weight-adjusted dose (Heysell et al., 2010; Mehta et
al., 2001; Peloquin, 2002; Kimerling et al., 1998). In our
study prevalance of low concentration of INH was 28.6%.
Sex, body mass index and dose of drug (mg/kg) were
effective factors in serum INH levels in this study.
Previous studies revealed that weight-adjusted dose
and a higher serum albumin level were associated with a
higher RIF concentration (Heysell et al., 2010; Mehta et
al., 2001). Patients with diabetes were at significantly
increased risk of having a low rifampin level. Diabetes
was significantly associated with slow response in a
study population, and, among persons with a slow
response with diabetes, 2 h levels of rifampsin were
significantly more likely to be below than the expected
ranges. Hyperglycemia can decrease gastric hydrochloric
acid secretion, which results in a higher gastric pH and
reduced rifampin absorption (Heysell et al., 2010). In this
study, patients enrolled to study were normoglycemic but
serum RIF levels were low in 75.5% of patients. Sex (to
be male) and smoking cigarette were found to be
associated variables in low RIF serum concentrations in
our study. Diabetic patients are at greater risk for incident
TB and are more likely to have poor TB treatment
outcomes, which may partially be explained by
inadequate pharmacotherapy (Jeon and Murray, 2008).
Dose-titration studies of rifampisin confirm a continuously
increasing response of early bactericidal activity by
measurement of sputum colony counts with
corresponding increase in rifampicin dose (Sirgel et al.,
2005; Diacon et al., 2007). As a result a second drug
dose adjustment has to be done to prevent from slow
response to therapy especially in patients with low RIF
serum levels.
A TDM study from South Korea reported low 2 h EMB
concentration ratio as 22.4% and an association between
EMB concentration and calculated creatinine clearance
(Mcllleron et al., 2006). We observed delayed EMB
absortion in seven of nine patients with low 2 h EMB
concentrations. 2 h EMB concentration was not found to
be associated with any of variables including calculated
creatinine clearence in our study. We have found the
prevalance of a low 2 h PZA concentration as 20.4%. The
mean concentration of males was lower than females.
Another result of the study is a correlation between 2 h
serum PZA concentration and drug dose. These
variables have accordance with previous studies (Um et
al., 2007; Mcllleron et al., 2006; Tappero et al., 2005).
Although an existence of high prevalance of low
antimycobacterial drug concentrations, treatment
outcomes included succesfull therapy results in the
present study. Early diagnosis, performing a directly
observing therapy in hospital, absence of extensive
disease and drug resistance may play role in this
condition. This study may support that all four antituberculosis
drugs should be dosed as mg/kg, smoking is
a negative factor in therapeutic RIF serum
concentrations. This study does not have an analysis
about TDM and slow response to therapy with clinical
outcomes in long periods of TB treatment. Another
limitation of present study is not having results of second
TDM after dose adjustment in low serum drug
concentrations. Thus further studies are required to