Ritonavir (ritonavir)

Ritonavir, an antiretroviral agent, is a human immunodeficiency virus (HIV) protease inhibitor (PI).

Ritonavir inhibits replication of retroviruses by interfering with HIV protease. The drug, therefore, exerts an effect against retroviruses by acting as an HIV protease inhibitor (PI). Through inhibition of HIV protease, processing of the Gag-Pol polyprotein precursor does not occur, which results in the production of immature, noninfectious HIV.

The pharmacokinetics of ritonavir have been studied in healthy adults and in adults with human immunodeficiency virus (HIV) infection. Pharmacokinetic studies have not revealed gender-related or race-related differences in the pharmacokinetics of ritonavir. In addition, there has been no evidence of age-related differences in the pharmacokinetics of the drug in adults 18-63 years of age.

Pharmacokinetics of the drug have been evaluated in a limited number of HIV-infected children 1 month of age or older. The pharmacokinetics of ritonavir in adults older than 63 years of age and in individuals with renal impairment have not been determined to date.

Ritonavir is well absorbed following oral administration, and peak plasma concentrations of the drug generally are attained within 2-4 hours. Following oral administration of a single 600-mg dose of radiolabeled ritonavir given as an oral solution, essentially all of the dose in systemic circulation represented unchanged ritonavir. Presence of food in the GI tract may affect the rate and/or extent of absorption of oral ritonavir; however, the effect that food has on GI absorption of ritonavir varies depending on the dosage form of the drug administered.

Administration of ritonavir tablets, or oral powder with food generally decreases the rate and extent of absorption of the drug. Administration of a single 100-mg ritonavir tablet with a high-fat (917 kcal, 60% fat) or moderate-fat meal results in a 21-23% decrease in ritonavir AUC and peak plasma concentration. Following administration of a single 100-mg dose of the oral powder with a moderate-fat or high-fat meal, the AUC and peak plasma concentration are decreased by 23-49% relative to fasting conditions.

Results of a limited study in HIV-infected children 2-14 years of age indicate that a ritonavir dosage of 350-400 mg/m2 twice daily results in plasma concentrations that approximate those reported in adults receiving a ritonavir dosage of 600 mg (approximately 330 mg/m2) twice daily. In HIV-infected infants 1-24 months of age receiving a ritonavir dosage of 350-450 mg/m2 twice daily, trough concentrations of ritonavir were lower than those reported in adults receiving a ritonavir dosage of 600 mg twice daily. Higher ritonavir exposures were not observed in infants receiving a ritonavir dosage of 450 mg/m2 twice daily compared with those receiving a dosage of 350 mg/m2 twice daily.

Results of a study in a limited number of HIV-infected adults indicate that use of a ritonavir dosage of 400 mg twice daily in patients with mild hepatic impairment results in similar ritonavir exposures as those reported in control individuals receiving 500 mg twice daily. In a limited number of adults with moderate hepatic impairment, administration of ritonavir 400 mg twice daily resulted in dose-normalized steady-state ritonavir exposures approximately 40% lower than that reported in adults with normal hepatic function receiving ritonavir 500 mg twice daily. Ritonavir is 98-99% bound to plasma proteins, principally serum albumin and alpha-1 acid glycoprotein, over a concentration range of 0.01-30 mcg/mL.

Mild or moderate hepatic impairment does not result in clinically important changes in protein binding of ritonavir. Limited data indicate that ritonavir is distributed into milk. The metabolic fate of ritonavir has not been fully determined, but the drug is metabolized in the liver.

Systemic clearance averages 8.8 L/hr in patients receiving ritonavir 600 mg every 12 hours or 4.6 L/hr in those receiving a single 600-mg dose. Renal clearance has been reported to be less than 0.1 L/hr. The plasma half-life of ritonavir in adults averages 3-5 hours.

Preliminary results of pharmacokinetic studies in HIV-infected children 1 month to 14 years of age indicate that ritonavir clearance at steady-state is 1.5--1.7 times greater in these children than in adults. Five ritonavir metabolites have been identified in human urine and feces. The isopropylthiazole oxidation metabolite (M2) appears to be the major metabolite.

M2 (but not other metabolites) has antiviral activity similar to that of ritonavir; however, only very low concentrations of this metabolite are present in plasma. Results of in vitro studies using human liver microsomes indicate that metabolism of ritonavir is mediated by P-450 CYP3A isoenzymes and, to a lesser extent, by CYP2D6; both CYP3A and CYP2D6 contribute to the formation of M2. Ritonavir is excreted principally in the feces, both as unchanged drug and metabolites.

Following oral administration of 600 mg of radiolabeled ritonavir as an oral solution, 86.4% of the dose is excreted in feces (33.8% as unchanged drug) and 11.3% of the dose is excreted in urine (3.5% as unchanged drug). Following continuous administration of ritonavir, plasma concentrations are lower than predicted from single-dose studies, presumably because of time- and dose-related increases in clearance. Because ritonavir is metabolized in the liver and is highly protein bound, it is unlikely that substantial amounts of the drug would be removed from the body by hemodialysis or peritoneal dialysis.

USES: This drug is used with other HIV medications to help control HIV infection. It helps to decrease the amount of HIV in your body so your immune system can work better. This lowers your chance of getting HIV complications (such as new infections, cancer) and improves your quality of life.

Ritonavir belongs to a class of drugs known as protease inhibitors. It increases ("boosts") the levels of other protease inhibitors, which helps these medications work better. Ritonavir is not a cure for HIV infection.

To decrease your risk of spreading HIV disease to others, continue to take all HIV medications exactly as prescribed by your doctor. Use an effective barrier method (latex or polyurethane condoms/dental dams) during sexual activity as directed by your doctor. Do not share personal items (such as needles/syringes, toothbrushes, and razors) that may have contacted blood or other body fluids.

Consult your doctor or pharmacist for more details.

Generic name: ritonavir
Pronunciation: (rye-TAWN-uh-veer)

The following indications are listed for Ritonavir:

• Hiv Infection

Also known as: Human Immunodeficiency Virus Disease, Human Immunodeficiency Virus Infection.

No ICD codes are available for this drug.