Ritonavir pharmacokinetics

Gallicano K, Choudhri S, Leclaire T, Poster BC. Effect of short-term administration of garlic supplements on single-dose ritonavir pharmacokinetics in healthy volunteers. Br J Clin Pharmacol 2003 55 199-202. 

Buss N, Snell P, Bock J, Hsu A, Jorga K. Saquinavir and ritonavir pharmacokinetics following combined ritonavir and saquinavir (soft gelatin capsules) administration. Br J Clin Pharmacol 2001 52(3) 255-64. 

In a further study, methadone apparently increased ritonavir exposure by 60%, when given alone, but had no effect on ritonavir pharmacokinetics when it was given with lopinavir. "... 

In a study in 16 healthy subjects the concurrent use of cetirizine 10 mg daily and ritonavir 600 mg twice daily for 4 days (after reaching steady-state ritonavir levels), increased the AUC of cetirizine by 42% with a slight 9% increase in maximum plasma levels. It was suggested that ritonavir may have decreased the renal excretion of cetirizine. The increase in cetirizine levels was not considered to be clinically relevant. Ritonavir pharmacokinetics were minimally affected by cetirizine. ... 

Ritonavir. When ritonavir 200 mg every 8 hours was given with clarithromycin 500 mg every 12 hours there were only minimal changes in ritonavir pharmacokinetics (12.5% increase in AUC and 15.3% increase in maximum plasma level). However, the AUC of clarithromycin increased by 77% with an almost total inhibition of 14-hydroxyclarithromycin formation (99.7% decrease in AUC). ... 

A woman had elevated serum digoxin levels and signs of toxicity after she was given ritonavir. Pharmacokinetic studies have shown that ritonavir causes modest to marked increases in singledose digoxin levels. 

Danner SA, Carr A, Leonard JM, Lehman LM, Gudiol F, Gonzales J, Raventos A, Rubio R, Bouza E, Pintado V et al (1995) A short-term study of the safety, pharmacokinetics, and efficacy of ritonavir, an inhibitor of HIV-1 protease, European-Australian Collaborative Ritonavir Study Group, N Engl J Med 333 1528-1533... 

HIV infection Saquinavir mesylate in combination with ritonavir and other antiretroviral agents is indicated for the treatment of HIV infection. The twice-daily administration of saquinavir mesylate in combination with ritonavir is supported by safety data from the MaxCmin 1 study and pharmacokinetic data. The efficacy of saquinavir mesylate with ritonavir or saquinavir soft gelatin capsules (with or without ritonavir coadministration) has not been compared against the efficacy of antiretroviral regimens currently considered standard of care. 

Dose adjustment for combination therapy with saquinavir For serious toxicities that may be associated with saquinavir mesylate, the drug should be interrupted. Saquinavir mesylate at doses less than 1,000 mg with ritonavir 100 mg twice daily are not recommended since lower doses have not shown antiviral activity. For recipients of combination therapy with saquinavir mesylate and ritonavir, dose adjustments may be necessary. These adjustments should be based on the known toxicity profile of the individual agent and the pharmacokinetic interaction between saquinavir and the coadministered drug. Health care providers should refer the complete monographs for these drugs for comprehensive dose adjustment recommendations and drug-associated adverse reactions of nucleoside analogues. 

Pharmacokinetics Peak concentrations of ritonavir were achieved approximately 2 and 4 hours after dosing under fasting and nonfasting conditions, respectively. The extent of absorption of ritonavir from the capsule formulation was 15% higher when administered with a meal. 

Children The safety and pharmacokinetic profiles of lopinavir/ritonavir in children under 6 months of age have not been established. In HIV-infected patients 6 months to 12 years of age, the adverse event profile seen during a clinical trial was similar to that for adult patients. The evaluation of the antiviral activity of lopinavir/ritonavir in... 

Hsn, A, Graimeman GR, Bertz RJ. Ritonavir clinical pharmacokinetics and interactions with other anti-HIV agents. Chn Pharmacokinet 1998 35 275-91. 

Ouellet D, Hsu A, Oian J, Locke CS et al. Effect of ritonavir on the pharmacokinetics of ethinyloestradiol in healthy female volunteers. Br J Clin Pharmacol 1998 46 111-16. 

F is 3 X hoger) ritonavir (600 mg daily or two or three times per week) is a possibility. However, the pharmacokinetic data and clinical experience for these combinations are limited. Coadministration of saquinavir HGC or saquinavir SGC with rifampicin (in the absence of ritonavir) is not recommended because rifampicin markedly decreases concentration of saquinavir... 

Atazanavir is an azapeptide PI with a pharmacokinetic profile that allows once-daily dosing. It should be taken with a light meal to enhance bioavailability. Atazanavir requires an acidic medium for absorption and exhibits pH-dependent aqueous solubility therefore, separation of ingestion from acid-reducing agents by at least 12 hours is recommended. Atazanavir is able to penetrate both the cerebrospinal and seminal fluids. The plasma half-life is 6-7 hours, which increases to approximately 11 hours when -administered with ritonavir. The primary route of elimination is biliary atazanavir should not be given to patients with severe hepatic insufficiency. 

The high aqueous solubility and largely nonpeptidic character of indinavir may be responsible for the good oral bioavailability, respectable pharmacokinetic profile, and high antiviral activity observed with this compound. Similar to saquinavir and ritonavir, indinavir has been recently approved by the FDA for treatment of AIDS. 

HIV PR inhibitors with acceptable oral availability and pharmacokinetic properties offer great promise for the treatment of HIV infection and AIDS. Efficacy studies of indinavir, ritonavir, or nelfinavir using plasma viral RNA as a marker have demonstrated up to three log reductions in RNA copy numbers that are... 

The pharmacokinetics of saquinavir is modified by agents that alter isoenzyme CYP3A4 of the cytochrome P-450 system and P-glycoprotein transporter. It should not be administered with midazolam, triazolam and ergot derivatives. The plasma concentrations of saquinavir are lower when coadministered with efavirenz, nevirapine or rifampin. Ritonavir reverses the effects of nevirapine on saquinavir. The coadministration of astemizole, terfenadine, amiodarone, bepridil, quinidine, propafenone or flecainide with saquinavir is also not recommended due to its potential for serious and/or life-threatening reactions. 

Healthy volunteers were given protease inhibitors and statins, and the authors concluded that simvastatin should be avoided and that atorvastatin could be used with caution in people taking ritonavir and saquinavir (111). Dosage adjustment of pravastatin may be necessary with co-administration of ritonavir and saquinavir. Pravastatin does not alter the pharmacokinetics of nelfinavir, and thus appears to be safe for co-administration. 

Corbett AH, Eron JJ, Fiscus SA, Rezk NL, Kashuba AD. The pharmacokinetics, safety, and initial virologic response of a triple-protease inhibitor salvage regimen containing amprenavir, saquinavir, and ritonavir. J Acquir Immune Defic Syndr 2004 36(4) 921-8. 

In its original formulation as a hard gel capsule (saquinavir-H Invirase), oral saquinavir was poorly bioavailable (about 4% in the fed state). It was therefore largely replaced in clinical use by a soft gel capsule formulation (saquinavir-S Fortovase), in which absorption was increased approximately threefold. However, reformulation of saquinavir-H for once-daily dosing in combination with low-dose ritonavir (see Ritonavir) has both improved antiviral efficacy and decreased the gastrointestinal side effects typically associated with saquinavir-S. Moreover, coadministration of saquinavir-H with ritonavir results in blood levels of saquinavir similar to those associated with saquinavir-S, thus capitalizing on the pharmacokinetic interaction of the two agents. 

---