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heamoglobin) (Table 2).
Serum EMB concentration
Figure 4. Ethambutol (EMB) serum levels of each patient < 2 µg/ml ; 18.4% (9/49) , n = 49.
The mean serum concentration of EMB was 3.68 ± 2.41
µg/ml and the mean EMB dose was 24.16 ±5.15 mg/kg
(Tables 1 and 2). The prevalance of a low 2 h EMB
concentration was 18.4% (9/49) (Figures 1 and 4). A
delayed absortion was observed in seven of nine low 2 h
EMB concentrations and they reached to therapeutic
serum levels at 6 h measurements. 2 h EMB
concentration was not found to be associated with any of
variables including calculated creatinine clearence in the
present study (Table 2).
Serum PZA concentration
The mean serum concentration of PZA was 32.20 ±
16.96 µg/ml and the mean PZA dose was 28.98 ± 8.65
mg/kg (Tables 1 and 2; Figure 5). The prevalance of a
low 2 h PZA concentration was 20.4% (10/49) (Figure
1). There was a difference between 2 h PZA
concentration and sex variable (p = 0.002). The mean
concentration of males (26.57 µg/ml) was lower than
females (41.88 µg/ml). Drug dose (mg/kg) was found to
be statistically significant in serum PZA concentration.
There was a correlation between 2 h serum PZA
concentration and drug dose (p = 0.005 and r = 0.395)
(Table 2).
Treatment outcomes
Complete outcomes were available for all patients. Fourty
nine patients succesfully completed treatment. No patient
Kayhan and Akgüneş 2039
had died during therapy and follow up. There was not any
treatment failure among the study cases. Median time to
completion of therapy among all 49 patients was 7.3
months (inter quartille range [IQR] 6 to 9 months). We did
not achieve a correlation between low antimycobacterial
drug levels and the time to completion of therapy. There
were no reports of relapse of infection over a median of 5
months (IQR 3 to 8 months) from the conclusion of
treatment. No patient had documented acquisition of
medication resistance in follow up TB cultures while on
treatment.
The 2 h value after ingestion of tuberculosis drugs is
the peak serum concentration of drugs in normal
patterns. Should the 2 and 6 h values be roughly the
same, perhaps somewhat below the expected ranges, or
should the 6 h levels be higher than the 2 h, delayed
absorption is most likely. In these situations, it is possible
that the actual peak occurred between the two intervals.
It is recommended to take the drugs under fasting
positions, especially for isoniazid and rifampicin.
Malabsorption is most likely if both 2 and 6 h serum drug
levels below the expected ranges, and consideration
should be given higher doses (Peloquin, 2002, Peloquin
et al., 1993). Second blood samples were taken after 6 h
to rule out the possibility of delayed absorption secondary
to poor gastric emptying in this study. We observed some
delayed absorptions and therapeutic drug levels after 6 h
in EMB (14.28%, 7/49), PZA (4.08%, 2/49), INH (2.04%,
1/49) and RIF (0%) respectively. The frequency of
delayed absorption has been rare in other cohorts for
which 2 and 6 h measurements were performed (Holland
et al., 2009).
According to previous studies, the prevalences of low
concentrations of anti-tuberculosis drugs showed wide
variations in TB patients, that is, 2 to 48% for INH, 5 to
78% for RIF and 2 to 41% for EMB (Mcllleron et al., 2006;
Mehta et al., 2001; Peloquin et al., 1996; Holland et al.,
2009; Chang et al., 2008; Fahimi et al., 2011). According