Pharmacokinetics of clarithromycin extended-release (ER) tablets in patients with AIDS.
BACKGROUND
Clarithromycin is a key agent in effective antimycobacterial therapy and prophylaxis for AIDS-related disseminated Mycobacterium avium complex (dMAC) infection. Immediate-release (IR) clarithromycin tablets are dosed at 500 mg bid for these indications. A new extended-release (ER) tablet of clarithromycin has been developed and approved at a dosing interval of once every 24 hours for treatment of respiratory tract bacterial infections. However, the pharmacokinetics of clarithromycin ER in AIDS patients with or at risk for dMAC has not been previously investigated.


METHODS
We conducted a randomized, crossover trial in which 14 AIDS patients received clarithromycin ER, 1000 mg once daily, and clarithromycin IR, 500 mg bid, each for 1 week, with pharmacokinetic sampling at the end of each week.


RESULTS
The mean of the individual AUC ratios for clarithromycin ER vs. IR was 1.09 (90% CI, 0.94-1.24). Adverse events were no more severe or frequent with clarithromycin ER than IR.


CONCLUSIONS
Clarithromycin ER is a once-daily regimen that is as well tolerated as standard bid IR clarithromycin dosing and has average bioequivalence to the IR formulation in patients with AIDS.
Jacobson
Mark A
MA
Positive Health Program, Department of Medicine, University of California San Francisco 94110, USA. mjacobson@php.ucsf.edu
Nicolau
David P
DP
Sutherland
Christina
C
Smith
Anna
A
Aweeka
Francesca
F
D000163:Acquired Immunodeficiency Syndrome / Q000150:complications; D000328:Adult; D000368:Aged; D019540:Area Under Curve; D017291:Clarithromycin / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D018592:Cross-Over Studies; D003692:Delayed-Action Preparations / Q000009:adverse effects / Q000493:pharmacokinetics; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D015270:Mycobacterium avium-intracellulare Infection / Q000188:drug therapy / Q000517:prevention & control
D003692:Delayed-Action Preparations; D017291:Clarithromycin