Pharmacokinetic evaluation of para-aminosalicylic acid granules.
OBJECTIVE
To determine the bioavailability and renal elimination of para-aminosalicylic acid (PAS) and its inactive metabolite acetyl-para-aminosalicylic acid (AcPAS) from a new PAS formulation.


METHODS
(a) Single-dose pharmacokinetic study in healthy volunteers; (b) Day-1 and day-8 pharmacokinetic comparison in patients with multidrug-resistant tuberculosis (MDR-TB).


METHODS
Referral hospital that specializes in the treatment of mycobacterial infections.


METHODS
(a) Twelve healthy male and female volunteers recruited by the investigators. Eleven subjects (92%) completed the study; one subject could not maintain venous access and was removed from the study. (b) Six sequential male and female patients receiving multidrug treatment for advanced MDR-TB. All patients completed the study.


METHODS
(a) Volunteers received a single 4-g dose of enteric-coated PAS granules administered with food. Blood and urine samples were collected over 24 hours after the dose. (b) Patients received 4-g doses of enteric-coated PAS granules every 8 hours for 7 days as part of their treatment regimen. Blood samples were obtained at approximately 2, 4, and 8 hours after the first dose on day 1 and the twenty-second dose on day 8.


RESULTS
Concentrations of PAS and AcPAS were determined using high-performance liquid chromatography. The serum concentration-time curves from volunteers and patients showed sustained PAS concentrations, in contrast to immediate-release sodium PAS tablets. In the six patients with tuberculosis, day 8 concentrations were considerably higher than those on day 1, and all were sustained well above the PAS minimal inhibitory concentration for Mycobacterium tuberculosis.


CONCLUSIONS
Para-aminosalicylic acid granules produce adequate serum concentrations and appear to be safe.
Peloquin
C A
CA
Department of Medicine, National Jewish Center for Immunology, Denver, CO 80206.
Henshaw
T L
TL
Huitt
G A
GA
Berning
S E
SE
Nitta
A T
AT
James
G T
GT
D000042:Absorption; D000328:Adult; D010131:Aminosalicylic Acid / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D000636:Aminosalicylic Acids / Q000097:blood / Q000493:pharmacokinetics*; D001682:Biological Availability; D004334:Drug Administration Schedule; D004352:Drug Resistance, Microbial; D005260:Female; D005502:Food; D006801:Humans; D008297:Male; D011208:Powders; D014376:Tuberculosis / Q000188:drug therapy / Q000378:metabolism*
D000636:Aminosalicylic Acids; D011208:Powders; C086759:acetyl 4-aminosalicylic acid; D010131:Aminosalicylic Acid