Hard gel saquinavir equivalent to soft gel when boosted

Keith Alcorn
Estimated reading time 2 minutes
This article is more than 23 years old.

Hard gel saquinavir (Invirase) may return to favour after being condemned as sub-optimal in the mid-90s, following the demonstration that Invirase boosted with ritonavir produces better blood levels and is better tolerated than the soft gel version (Fortovase).

The soft gel formulation of saquinavir (Fortovase) is poorly tolerated by some people with HIV when boosted with ritonavir, due to diarrhea. German researchers reported a 24 day study in 24 HIV-negative volunteers in which participants were randomized to receive 1000mg of saquinavir in the form of either Invirase or Fortovase, plus 100mg of ritonavir as a booster. After 14 days, participants underwent a 24 hour pharmacokinetic profile to analyse the dynamics of saquinavir levels. They then switched to the other dose, and underwent another 24 hour evaluation ten days later.

The average saquinavir trough level was significantly higher in the Invirase group than the Fortovase group (383 ng/mL vs 237 ng/mL; p=0.0017), and gastrointestinal side effects were more common in the Fortovase group (18 cases of diarrhoea vs 5 in the Invirase group).

Glossary

boosting agent

Booster drugs are used to ‘boost’ the effects of protease inhibitors and some other antiretrovirals. Adding a small dose of a booster drug to an antiretroviral makes the liver break down the primary drug more slowly, which means that it stays in the body for longer times or at higher levels. Without the boosting agent, the prescribed dose of the primary drug would be ineffective.

diarrhoea

Abnormal bowel movements, characterised by loose, watery or frequent stools, three or more times a day.

gastrointestinal (GI) symptoms

Relating to or affecting the gut, stomach or bowel. GI symptoms include diarrhoea, abdominal pain (cramps), constipation, gas in the gastrointestinal tract, nausea, vomiting and GI bleeding. Among several possible causes of GI symptoms are infections and antiretroviral medicines.

 

trough level

The lowest point to which levels of a drug fall in the blood between doses.

 

protease inhibitor (PI)

Family of antiretrovirals which target the protease enzyme. Includes amprenavir, indinavir, lopinavir, ritonavir, saquinavir, nelfinavir, and atazanavir.

These findings are likely to encourage Roche, manufacturer of saquinavir, to pursue the development of Invirase as a once daily protease inhibitor boosted by ritonavir, on the grounds that it is likely to be better tolerated. Once daily dosing is being explored for several protease inhibitors (see

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A comparative study of once daily saquinavir/ritonavir versus efavirenz recently produced discouraging

news on the tolerability of once daily Fortovase; nearly one third of participants discontinued Fortovase treatment within six months due to side effects, almost entirely GI-related.

Commenting on the Invirase findings, Dr Mike Youle of the Royal Free Hospital in London said: "We have been switching patients on ritonavir/saquinavir from Fortovase to Invirase for some time because it is better tolerated, and it will obviously help if a 500mg Invirase tablet is developed, making this boosted PI into three pills once daily".

References

Kurowski M et al. Comparative pharmacokinetics and short-term safety of twice daily (BID) Fortovase/ritonavir and Invirase/ritonavir. Ninth Conference on Retroviruses and Opportunistic Infections, Seattle, abstract 432, 2002.

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