Low antituberculosis drug concentrations in patients with AIDS.
OBJECTIVE
To determine the frequency and magnitude of below normal apparent peak serum concentrations for antituberculosis drugs in patients with AIDS and CD4 cell counts less than 200 cells/mm3. We also explored the data for potential relationships between response variables and patient characteristics.


METHODS
Prospective study of consecutive patients seen in tuberculosis clinics.


METHODS
Five urban tuberculosis clinics in four major metropolitan areas.


METHODS
Twenty-six patients diagnosed with HIV infection and receiving treatment for active tuberculosis were eligible.


METHODS
After 2 weeks or more of therapy, blood was collected 2 hours after observed doses of the antituberculosis drugs. Serum samples were frozen, shipped to National Jewish Center in Denver, and analyzed by HPLC or GC. Serum concentrations were compared with the proposed normal ranges. Data were analyzed to determine correlations between antituberculosis drug serum concentrations and patient characteristics.


RESULTS
Low-2-hour serum concentrations were common for antituberculosis drugs, particularly rifampin and ethambutol. Absorption of isoniazid was generally high. Potential drug-drug interactions were found between rifampin and fluconazole (fluconazole appears to increase rifampin concentrations) and between pyrazinamide and zidovudine (zidovudine may lower pyrazinamide concentrations). Patients receiving pyrazinamide had lower rifampin concentrations than those not receiving pyrazinamide.


CONCLUSIONS
Low antituberculosis drug serum concentrations occur frequently during the treatment of tuberculosis in patients with AIDS. Additional research is required for patients with drug-resistant tuberculosis, and to clarify the nature of the potential drug-drug interactions.
Peloquin
C A
CA
Nitta
A T
AT
Burman
W J
WJ
Brudney
K F
KF
Miranda-Massari
J R
JR
McGuinness
M E
ME
Berning
S E
SE
Gerena
G T
GT
D000328:Adult; D019380:Anti-HIV Agents / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use; D000935:Antifungal Agents / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use; D000995:Antitubercular Agents / Q000097:blood* / Q000493:pharmacokinetics / Q000627:therapeutic use; D004347:Drug Interactions; D005260:Female; D015725:Fluconazole / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use; D015658:HIV Infections / Q000097:blood* / Q000188:drug therapy; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011718:Pyrazinamide / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use; D012293:Rifampin / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use; D014397:Tuberculosis, Pulmonary / Q000097:blood* / Q000188:drug therapy; D015215:Zidovudine / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use
D019380:Anti-HIV Agents; D000935:Antifungal Agents; D000995:Antitubercular Agents; D011718:Pyrazinamide; D015215:Zidovudine; D015725:Fluconazole; D012293:Rifampin