Abstract
The first dose (FD) and steady state (SS) pharmacokinetics of orally administered TMP-SMX was evaluated in 15 patients with CF. The biodisposition of the TMP and SMX were regulated independently and no fixed ratio of the TMP to SMX was maintained. The FD and SS pharmacokinetic parameters for TMP were determined using a single compartment model. Data are given in the table below. When the FD and SS data for SMX were similarly analyzed using either a one- or two-compartment model large interindividual differences in biodisposition were observed. At least half the patients were found to have saturable SMX elimination pathways and total SMX absorption was found to increase markedly with continued therapy (AUCSS>AUCFD;∼3-fold). These results suggest that the biodisposition of TMP-SMX in patients with CF is markedly different from that observed in unaffected individuals. Because of the independent biodisposition of TMP and SMX and the large interindividual differences in SMX elimination kinetics, the administration of these drugs in CF patients may be more effective as single agents.
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