The study objective was to determine the minimum frequency of dosing for st
andard 4-g doses of p-aminosalicylic acid (PAS) granules. Two sequential si
x-patient pharmacokinetic studies are described, followed by clinical data
from 40 subsequent patients. All patients had multidrug-resistant tuberculo
sis (MDR-TB), Serum was collected at two to three time points after dosing)
and assayed by a validated high performance liquid chromatography (HPLC) a
ssay. Data were analyzed using noncompartmental methods. In six patients, t
wice-daily dosing produced median serum concentrations at. 4, 8, and 12 h p
ost-dose of 25.8, 23.2 and 16.4 mu g/ml. In six patients, once-daily dosing
produced median serum concentrations at 6, 12 and 24 h post-dose of 23.4,
3.7, and 0 mu g/ml. in 40 patients, twice-daily dosing produced median seru
m concentrations at 4 to 8 and 9 to 12 h post-dose of 24.8 and 20.6 mu g/ml
. Unlike once-daily dosing, twice-daily PAS maintained serum concentrations
in excess of 1 mu g/ml, the typical minimal inhibitory concentration again
st Mycobacterium tuberculosis, for the entire dosing Interval. We now use t
wice-daily PAS granules for our patients with MDR-TB.