Once-daily and twice-daily dosing of p-aminosalicylic acid granules.
The study objective was to determine the minimum frequency of dosing for standard 4-g doses of p-aminosalicylic acid (PAS) granules. Two sequential six-patient pharmacokinetic studies are described, followed by clinical data from 40 subsequent patients. All patients had multidrug-resistant tuberculosis (MDR-TB). Serum was collected at two to three time points after dosing, and assayed by a validated high performance liquid chromatography (HPLC) assay. Data were analyzed using noncompartmental methods. In six patients, twice-daily dosing produced median serum concentrations at 4, 8, and 12 h post-dose of 25.8, 23.2, and 16.4 microgram/ml. In six patients, once-daily dosing produced median serum concentrations at 6, 12, and 24 h post-dose of 23.4, 3.7, and 0 microgram/ml. In 40 patients, twice-daily dosing produced median serum concentrations at 4 to 8 and 9 to 12 h post-dose of 24.8 and 20.6 microgram/ml. Unlike once-daily dosing, twice-daily PAS maintained serum concentrations in excess of 1 microgram/ml, the typical minimal inhibitory concentration against Mycobacterium tuberculosis, for the entire dosing interval. We now use twice-daily PAS granules for our patients with MDR-TB.
Department of Medicine, National Jewish Medical and Research Center, University of Colorado, Denver, Colorado, USA. peloquinc@njc.org
C A
CA
Peloquin
S E
SE
Berning
G A
GA
Huitt
J M
JM
Childs
M D
MD
Singleton
G T
GT
James
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D010131:Aminosalicylic Acid / Q000008:administration & dosage* / Q000493:pharmacokinetics; D000995:Antitubercular Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D002851:Chromatography, High Pressure Liquid; D004304:Dosage Forms; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D018088:Tuberculosis, Multidrug-Resistant / Q000097:blood / Q000188:drug therapy*
D000995:Antitubercular Agents; D004304:Dosage Forms; D010131:Aminosalicylic Acid