Saquinavir mesylate is a different formulation, designed to be combined with another protease inhibitor that increases the bioavailability of the saquinavir.

History

Saquinavir was the first protease inhibitor (and sixth antiretroviral) approved by the Food and Drug Administration (FDA). It was approved on December 6, 1995, as Invirase®, a poorly-absorbed hard gel capsule which quickly led to viral resistance in many of the pioneer patients.

It was approved again on Nov 7, 1997 as Fortovase®, a soft gel capsule reformulated for improved bioavailability. The manufacturer, Roche, is alleged to have rushed Invirase® to market, but the conditions that prevailed at the time were very bad and there was a lot of pressure to produce products quickly.

Method of activity

When given alone, the HIV Protease Inhibitor (HPI) saquinavir has a very low oral bioavailability. In the clinic, it was found that the oral bioavailability of saquinavir significantly increases when patients also receive the HPI ritonavir. For patients, this has the major benefit that they can take less saquinavir, while maintaining sufficient saquinavir blood plasma levels to efficiently suppress the replication of HIV.

The mechanism behind this welcome observation was not directly known, but later it was determined that ritonavir inhibits the enzyme Cytochrome P450 3A4. Normally, this enzyme metabolizes saquinavir to an inactive form, but with the ritonavir inhibiting this enzyme, the saquinavir blood plasma levels increased considerably. Additionally, ritonavir also inhibits multidrug transporters, although to a much lower extent.

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Take a pill break - HIV Digest - intermittent drug therapy in AIDS treatment; includes related notes - Brief Article
From Men's Fitness, 3/1/02

People with AIDS may be able to take weeklong vacations from their drug regimens, according to a study at the National Institute of Allergy and Infectious Diseases in Bethesda, Md.

While continuous highly active antiretroviral therapy is effective for many patients, it can be complex, expensive and rife with side effects. "Intermittent therapy may be an important strategy to reduce the cost and toxicity for HIV-infected individuals," reports lead author Mark Dybul, M.D.

A small group of patients with low levels of the virus and high CD4 counts were cycled on and off their drugs every seven days for up to 88 weeks. Viral levels remained suppressed for every patient who stayed with the schedule. An additional benefit was that cholesterol and triglyceride levels dropped by an average of 50 percent and 22 percent, respectively.

Past the seven-day break, however, viral loads increased. "This means that these patients will be on the drugs for the rest of their lives," confirms Dybul.

The results were published in the Proceedings of the National Academy of Sciences.

RURAL CARE AIN'T UP TO SNUFF

Country living may provide numerous benefits, but quality HIV health care isn't one of them, according to a report in the Journal of Acquired Immune Deficiency Syndromes. Patients who live in rural areas are less likely than those in urban areas to be taking the medications they need to reduce viral loads and protect them from pneumonia.

"Rural health care suffers from physician shortages, underdeveloped social and home-care support systems, and long travel distances to care," concludes lead author Susan E. Cohn, M.D., of the University of Rochester, New York.

In their survey, investigators discovered that 57 percent of rural patients were taking highly active antiretroviral therapy and 60 percent were getting pneumonia-prevention treatment. The respective totals for urban patients were 73 percent and 75 percent. Rural doctors were also less likely to be experienced with HIV and less knowledgeable about the best treatment strategies.

In addition to calling for educational efforts, the report advocates "channeling patients to higher volume local providers providing transportation to regional experts, and/or increasing co-management or telemedicine consulting between rural clinicians and HIV experts."

GARLIC CAN REPEL CRIXIVAN

Standard doses of garlic caplets can cut blood levels of the protease inhibitor saquinavir (brand name Crixivan) by 50 percent, according to a study conducted by the National Institute of Allergy and Infectious Diseases. Even after discontinuing the garlic supplements, concentrations of the antiretroviral drug remained depressed by 35 percent for as much as 10 days. Apparently, garlic and protease inhibitors share the same metabolic route, though the exact nature of the impedance is still unknown.

As the use of alternative therapies has increased dramatically, doctors have discovered a number of incompatibilities with prescription drugs. An earlier study revealed a potentially dangerous interaction between St. John's wort and the protease inhibitor indinavir (brand name Invirase).

The results were published in the online edition of the journal Clinical Infectious Diseases.

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