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Letters
June 14, 2000

Effect of Ritonavir on Saquinavir Metabolism

Author Affiliations
 

Phil B.FontanarosaMD, Deputy EditorIndividualAuthorStephen J.LurieMD, PhD, Contributing EditorIndividualAuthor

JAMA. 2000;283(22):2936-2937. doi:10.1001/jama.283.22.2931

To the Editor: The Consensus Statement on antiretroviral therapy in adults by Dr Carpenter and colleagues1 contains an inaccuracy regarding the effect of coadministration of ritonavir on the exposure of saquinavir in the soft-gelatin formulation (saquinavir SGF). Table 2 states that ritonavir coadministration results in an increase in saquinavir exposure (area under the plasma concentration curve [AUC]) of 121%. This estimate, however, is too low by greater than an order of magnitude.2

The increase of 121% results from a comparison of the 24-hour saquinavir exposures obtained with the combination of 400 mg of ritonavir twice daily plus 400 mg of saquinavir SGF twice daily against exposures obtained with saquinavir SGF, 1200 mg, administered 3 times daily (the licensed dosage).3,4 This comparison was previously presented because it was considered to be clinically meaningful in view of the wide use of the ritonavir, 400 mg, and saquinavir SGF, 400 mg, twice daily dosage combination in clinical practice.

When saquinavir SGF and ritonavir are coadministered, the doses of both drugs should be adjusted because of the substantial effect of ritonavir on the metabolism of saquinavir.

References
1.
Carpenter  CCCooper  DAFischl  MA  et al.  Antiretroviral therapy in adults: updated recommendations of the International AIDS Society–USA Panel.  JAMA. 2000;283:381-390.Google Scholar
2.
Jorga  KBuss  NEfor the Fortovase Study Team, Pharmacokinetic (PK) drug interactions with saquinavir soft gelatin capsule. From: 39th Interscience Conference on Antimicrobial Agents and Chemotherapy; September 26-29, 1999; San Francisco, Calif. Abstract 339.
3.
Buss  Nfor the Fortovase Study Group, Saquinavir soft gel capsule (Fortovase): pharmacokinetics and drug interactions. From: 5th Conference on Retroviruses and Opportunistic Infections; February 1-5, 1998; Chicago, Ill. Abstract 354.
4.
 Fortovase [package insert]. Nutley, NJ: Roche Laboratories Inc; 1997.
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