Para-aminosalicylic acid (PAS)

Yusuke Minato, Anthony Baughn

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

para-Aminosalicylic acid (PAS) is one of the oldest antitubercular drugs, and first entered clinical use in 1944 (Lehmann, 1946). PAS (chemical structure shown in Figure 131.1), a structural analog of the folate precursor paraaminobenzoic acid (PABA), is a prodrug that is activated within the Mycobacterium tuberculosis folate biosynthetic pathway and ultimately inhibits dihydrofolate reductase (DHFR) (Chakraborty et al., 2013; Zheng et al., 2013; reviewed in Minato et al. 2015). Early multidrug therapy regimens including combinations of PAS, streptomycin, and isoniazid resulted in a significant increase in tuberculosis (TB) cure rates relative to mono- and dual therapy regimens (reviewed in Fox, 1979). Until the mid-1960s PAS was a standard component of the first-line multidrug regimen for the treatment of TB. However, PAS treatment was commonly associated with gastrointestinal disturbance and other severe adverse reactions, and was replaced with a better-tolerated companion agent, ethambutol (Ferebee et al., 1966). A subsequently developed gastroresistant delayed-release granule formulation of the free base of PAS (GR-PAS or Paser) has shown significantly reduced gastrointestinal disturbance (Peloquin et al., 1994; Peloquin et al., 1999). In response to the recent global spread of multidrug-resistant (MDR; resistant to isoniazid and rifampin) and extensively drug-resistant (XDR; resistant to isoniazid, rifampin, fluoroquinolones, and any second-line injectable drug) strains of M. tuberculosis, PAS has re-entered antitubercular drug regimens as an important second-line agent (Donald and Diacon, 2015).

Original languageEnglish (US)
Title of host publicationKucers the Use of Antibiotics
Subtitle of host publicationA Clinical Review of Antibacterial, Antifungal, Antiparasitic, and Antiviral Drugs, Seventh Edition
PublisherCRC Press
Pages2488-2492
Number of pages5
ISBN (Electronic)9781498747967
ISBN (Print)9781498747950
DOIs
StatePublished - Jan 1 2017

Fingerprint Dive into the research topics of 'Para-aminosalicylic acid (PAS)'. Together they form a unique fingerprint.

  • Cite this

    Minato, Y., & Baughn, A. (2017). Para-aminosalicylic acid (PAS). In Kucers the Use of Antibiotics: A Clinical Review of Antibacterial, Antifungal, Antiparasitic, and Antiviral Drugs, Seventh Edition (pp. 2488-2492). CRC Press. https://doi.org/10.1201/9781315152110