Ritonavir (trade name Norvir) is an antiretroviral compound from the protease inhibitor class used to treat HIV infection and AIDS. Ritonavir (ABT-538) induces CYP 1A2 and inhibits the major P450 isoforms (3A4 and 2D6). Ritonavir is frequently prescribed with HAART, not for its antiviral action, but as it inhibits the same host enzyme that metabolizes other protease inhibitors, allowing the clinician to lower their dose and frequency and improving their clinical efficacy. More specifically, ritonavir (ABT-538) is used to inhibit a particular liver enzyme that normally metabolizes protease inhibitors, cytochrome P450-3A4 (CYP3A4). Ritonavir's inhibition of the cytochrome P-450 CYP3A4 enzyme reduces the metabolism of concomitantly administered protease inhibitors and changes their pharmacokinetic parameters, including area under the curve (AUC), maximum concentration (Cmax), minimum concentration (Cmin) and half-life (t1/2). As a result, the bioavailability of the boosted protease inhibitor is increased and improved penetration into HIV reservoirs may be achieved.
|Body Surface Area (m2)||0.007||0.025||0.15||0.05||0.02||0.5|
|Animal A (mg/kg) = Animal B (mg/kg) multiplied by||Animal B Km|
|Animal A Km|
For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.
|Solubility||DMSO 80 mg/mL|
Pharmacological and therapeutic properties of ritonavir-boosted protease inhibitor therapy in HIV-infected patients.
Zeldin RK, et al. J Antimicrob Chemother. 2004 Jan;53(1):4-9. PMID: 14657084.
Elucidation of crystal form diversity of the HIV protease inhibitor ritonavir by high-throughput crystallization.
Morissette SL, et al. Proc Natl Acad Sci U S A. 2003 Mar 4;100(5):2180-4. PMID: 12604798.
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