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A Comparison of the Single-dose Bioavailability of a Ritonavir Tablet Formulation Compared with the Current Soft Gel Capsule

Ritonavir (Norvir) has been approved by regulatory agencies worldwide and is indicated for use in combination with other antiretroviral agents for the treatment of HIV infection. Due to its cytochrome P450 inhibition properties, ritonavir dosed 100 mg once-daily (QD) to 200 mg twice-daily (BID) is frequently used as a pharmacokinetic enhancer of other antiretrovirals, including protease inhibitors.

A tablet formulation of lopinavir/ritonavir (Kaletra) recently has been approved in many countries worldwide. This tablet does not require refrigeration. In the current Phase I, open-label, randomized, crossover study, presented at the XVII International AIDS conference last week in Mexico City (August 3-8, 2008), researchers assessed the bioavailability of the currently marketed soft gelatin capsule (SGC) compared to a new tablet formulation with potentially improved stability compared to prior pilot tablet formulations.

A total of 24 healthy HIV negative volunteers enrolled in this 2-period, single dose study received a 100 mg dose of ritonavir test tablet or the currently marketed SGC following a meal with moderate fat content. Serial blood samples were collected for 36 hours after dosing in each period.

The pharmacokinetic parameters of ritonavir were assessed using area under the plasma concentration time curve (AUC) and maximum plasma concentration (Cmax). Along with its safety, the bioavailability of the tablet formulation relative to the SGC was determined by the 2 1-sided test procedures via 90% confidence intervals.

Results

• The point estimates for ritonavir AUC was 20% higher and Cmax was 35% higher after administration of the tablet compared to the SGC.
• The increase in ritonavir exposure with the lopinavir/ritonavir tablet is not associated with a change in safety or tolerability compared with the SGC.

In conclusion, the study investigators concluded, "Ritonavir AUC after administration of the tablet was bioequivalent to the currently marketed SGC. The ritonavir Cmax upper bound of the 90% confidence interval exceed 1.25, which may be due, in part, to more efficient absorption of the tablet formulations."

In addition, they noted, "The higher Cmax of ritonavir tablet is unlikely to impact the safety profile or pharmacokinetic enhancing profile compared to the ritonavir SGC."

Abbott Laboratories, Abbott Park, IL.

8/12/08

Reference

J Ng, CE Klein, SJ Causemaker, and others. A Comparison of the Single Dose Bioavailability of a Ritonavir Tablet Formulation Relative to the Ritonavir Soft Gel Capsule in Healthy volunteers. XVII International AIDS Conference (AIDS 2008). Mexico City. August 3-8, 2008. Poster TUPE0076.