Interventions for Tuberculosis Control and Elimination 2002

activity in experimental models. 256 The use of para-aminosalicylic acid
became a core component in early combination therapy until its replacement
by the better tolerated ethambutol. 122
It is likely that para-aminosalicylic acid, and not streptomycin, was the
first anti-tuberculosis drug tested specifically against M. tuberculosis, as suggested
in an editorial 1029 and correspondence of Lehman (reproduced with
the permission of the South African Medical Journal): 1030,1031
“Dear Dr Dubovsky,
Your letter to the Director of the Central Laboratory at Sahlgrens
Hospital was forwarded to me. It was the most remarkable letter I
have received for many years. You are the first outside Sweden who
has paid attention to the fact that PAS was in clinical use before streptomycin,
eight months before ... Perhaps you wonder why I published
the first paper on PAS so long after it was taken in clinical use. The
reason was that as Ferrosan, a small company, had not taken out a
patent on PAS, I didn’t dare to publish the formula on PAS as other
greater companies could take over the production of PAS ...”
The MIC of M. tuberculosis is 1 mg/L. 1032
In analogy with the observation that benzoic acid inhibits the respiration
of tubercle bacilli, 1027 para-aminosalicylic acid might be built into coenzyme
F of the bacterium instead of para-aminobenzoic acid, and thereby
inhibit growth. 430
Maximum serum concentrations with twice 4 g granular para-aminosalicylic
acid are achieved within five to eight hours and remain above the
minimum inhibitory concentration over the entire dosing interval. 1032
The granular form of para-aminosalicylic acid is better tolerated than
the previously used tablet form. A dosage of 4 g twice daily of the granular
form produces serum concentrations above the minimum inhibitory
concentration over the entire dosing interval. 1032 Good experiences with
infusion therapy have also been reported. 1033
Para-aminosalicylic acid has been an unpleasant drug to take because
of the bulk required and the frequency of adverse drug events, 1034 which
include gastrointestinal and cutaneous adverse drug events. 1035 Para-aminosalicylic
acid may cause hypothyroidism, 1036,1037 and intestinal malabsorption.
1038,1039 Among hematologic changes are thrombocytopenia in
adults 1040,1041 and children. 1042
Para-aminosalicylic acid has been reported to increase isoniazid blood
levels. 1043-1045 It may cause hypoglycemia in diabetics. 1046
157