The aim of the study was to examine the relationships between N-acetyltransferase genotypes, pharmacokinetics, and tolerability of granular slow-release (GSR) para-aminosalicylic acid (PAS) in tuberculosis patients. The study was a randomized, two-period, open-label, cross-over design wherein each patient received GSR-PAS 4 g twice daily or GSR-PAS 8 g once daily alternately. The PAS concentration-time profiles were modeled by a one-compartment disposition model with three transit compartments in series to describe its absorption. Patients' NAT1 and NAT2 genotypes were determined by sequencing and restriction enzyme analysis, respectively. The number of daily vomits was modeled by a Poisson probability mass function. Comparisons of other tolerability measures by regimens, gender and genotypes were evaluated by linear mixed effects model. The covariate effects associated with efavirenz, gender, NAT1*3, NAT1*14, and NAT2*5 alleles corresponded to 25%, 37%, -17%, -48% and -27% change, respectively, in oral clearance of PAS. NAT1*10 allele did not influence drug clearance.

 

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