Hijazi Y, Riek M, Gaudeul-Ehrhart E, Grange S; IAS Conference on HIV Pathogenesis and Treatment (2nd : 2003 : Paris, France).
Antivir Ther. 2003; 8 (Suppl.1): abstract no. 534.
Roche, Basel, Switzerland
Saquinavir (SQV) is available as Invirase (INV) and Fortovase 200 mg capsules. These formulations have shown good efficacy and safety when boosted with ritonavir (r) at a dosage regimen of 1000 mg SQV/100 mg ritonavir bid. However, there remains the high pill count of SQV (5 capsules bid). Roche developed a 500 mg SQV tablet to reduce the pill count using aqueous granulation technology and standard excipients. A relative bioavailability study was performed to compare the SQV 500 mg tablet with the existing Invirase 200 mg capsule. This was an open-label, randomized, four-period, two-treatment, two-sequence, replicated, crossover design, with a washout period of 2 days. Twenty healthy male volunteers were treated with ritonavir at 100 mg bid for 24 days and were randomized to SQV 500 mg tablet or Invirase 200 mg capsules at 1000 mg single oral dose taken after a standard high fat breakfast on days 14, 17, 20 and 23. Blood samples were collected over 24 h after SQV administration and were analysed by a validated HPLC-MS/MS method. Pharmacokinetic parameters were estimated by non-compartmental methods. Four out of 20 subjects withdrew from the study one of which was due to an adverse event (GI). The results from 16 subjects were evaluable for bioavailability assessment. The geometric mean AUC0-$#165; (CV%) was 21433 ng*h/ml (58%) after INV/r and 22460 ng*h/ml (52%) after SQV 500 mg tablet/r. The geometric mean Cmax (CV%) was 2930 ng/ml (48%) and 3298 ng/ml (46%) after INV/r and SQV 500 mg tablet/r, respectively. The estimated mean exposure ratio (90% CI) of SQV 500 mg tablet/r versus INV/r was 1.05 (0.94; 1.17) for AUC0-$#165; and 1.13 (1.00; 1.26) for Cmax. In conclusion, the bioavailability of the new SQV 500 mg tablet was similar to that of Invirase when administered to healthy volunteers in combination with ritonavir under fed conditions. The new 500 mg tablet could replace both the existing Invirase and Fortovase 200 mg capsules when co-administered with ritonavir and hence improve adherence by reducing pill count for HIV patients treated with SQV/r.
Publication Types:
Keywords:
- Acquired Immunodeficiency Syndrome
- Biological Availability
- Capsules
- Carrier Proteins
- HIV Infections
- HIV Seropositivity
- Humans
- Male
- Ritonavir
- Saquinavir
Other ID:
UI: 102262816
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