Indinavir

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Better Known as: Crixivan

Mechanism of Action

Pharmacokinetics

HIV Protease Inhibitor Pharmacokinetics[1][2][3][4][5][6][7][8]
Parameter Ritonavir Tipranavir Indinavir Saquinavir Amprenavir Fosamprenavir Lopinavir Darunavir Atazanavir Nelfinavir
Tmax (hr) 4.4 ~3 Indinavir Saquinavir .98 Fosamprenavir Lopinavir .5 2-4 Nelfinavir
Cmax (ng/ml) 13120 14600 Indinavir 1540 4901 Fosamprenavir Lopinavir 2730 ~4393 4381
Bioavailability (%) Ritonavir Tipranavir 65 Saquinavir Amprenavir Fosamprenavir Lopinavir Darunavir 68 Nelfinavir
Protein Binding (%) 99 >99 61 98 90 90 99 95 86 98
T1/2 (hr) 4.8 4.2 1.8 4.5 5.5 7.7 Lopinavir 29.4 5.3 3.3
AUC (ng/ml/hr) 128100 46500 Indinavir 16200 11999 Fosamprenavir Lopinavir 4746 ~26045 27000
Clearance (L/h) Ritonavir 32.4 Indinavir Saquinavir 56.76 Fosamprenavir Lopinavir Darunavir Atazanavir Nelfinavir
Dosage (mg) 600 600 Indinavir Saquinavir 600 Fosamprenavir Lopinavir 400 400 750
Metabolism Hepatic (CYP3A4) Hepatic (CYP3A4) Hepatic (CYP3A4) Hepatic (CYP3A4) Amprenavir Hepatic (CYP3A4) Hepatic (CYP3A4) Hepatic (CYP3A4) Atazanavir Hepatic (CYP3A4)

Pharmacokinetics

HIV Protease Inhibitor Resistance Profile
Inhibitor/Mutation Site Leu 10 Lys 20 Leu 24 Asp 30 Val 32 Leu 33 Met 36 Met 46 Iso 47 Gly 48 Iso 50 Phe 53 Iso 54 Leu 63 Ala 71 Gly 73 Val 77 Val 82 Iso 84 Asp 88 Leu 90
Ritonavir F, I, R, V M, R - - I F I I, L - - - - V, L - V, T - I A, F, T, S V - M
Tipranavir & Ritonavir I, V M, L, T - - - I, F, V - I - - - - V - - - - A, F, L, T V - M
Indinavir I, R, V M, R I - I - I I, L - - - - V - V, T S, A I A, F, T V - M
Saquinavir I, R, V - - - - - - - - V - - V, L - V, T S I A V - M
Amprenavir or Fosamprenavir F, I, R, V - - - I - - I, L V - V - L, V, M - - S - - V - M
Lopinavir & Ritonavir F, I, R, V M, R I - I F - I, L V, A - V L V, L, A, M, T, S P V, T S - A, F, T, S V - M
Darunavir - - - - I F - - V - V - M, L - - S - - - - -
Atanzavir I, F, V R, M, I I - I I, F, V I, L, V I - V L - L - V C, S, T, A - A V S M
Nelfinavir F, I - - N - - I I, L - - - - - - V, T - I A, F, T, S V D, S M


References

  1. ↑ Goebel FD, MacGregor TR, Sabo JP, Castles M, Johnson PA, Legg D, McCallister S. Pharmacokinetic characterization of three doses of tipranavir boosted with ritonavir on highly active antiretroviral therapy in treatment-experienced HIV-1 patients. HIV Clin Trials. 2010 Jan-Feb;11(1):28-38. PMID:20400409 doi:10.1310/hct1101-28
  2. ↑ Ferry et al, United States Patent US6147095, Pharmacia & Upjohn Company.
  3. ↑ L. Veronese et al. Single-Dose Pharmacokinetics of Amprenavir, a Human Immunodeficiency Virus Type 1 Protease Inhibitor, in Subjects with Normal or Impaired Hepatic Function. Antimicrob Agents Chemother. 2000 April; 44(4): 821–826.
  4. ↑ J. Ford, et al. Intracellular and Plasma Pharmacokinetics of Saquinavir-Ritonavir, Administered at 1,600/100 Milligrams Once Daily in Human Immunodeficiency Virus-Infected Patients. Antimicrob Agents Chemother. 2004 July; 48(7): 2388–2393.
  5. ↑ Remmel RP, Kawle SP, Weller D, Fletcher CV. Simultaneous HPLC assay for quantification of indinavir, nelfinavir, ritonavir, and saquinavir in human plasma. Clin Chem. 2000 Jan;46(1):73-81. PMID:10620574
  6. ↑ Fuster D, Clotet B. Review of atazanavir: a novel HIV protease inhibitor. Expert Opin Pharmacother. 2005 Aug;6(9):1565-72. PMID:16086644 doi:10.1517/14656566.6.9.1565
  7. ↑ Vermeir M, Lachau-Durand S, Mannens G, Cuyckens F, van Hoof B, Raoof A. Absorption, metabolism, and excretion of darunavir, a new protease inhibitor, administered alone and with low-dose ritonavir in healthy subjects. Drug Metab Dispos. 2009 Apr;37(4):809-20. Epub 2009 Jan 8. PMID:19131522 doi:10.1124/dmd.108.024109
  8. ↑ von Moltke LL, Durol AL, Duan SX, Greenblatt DJ. Potent mechanism-based inhibition of human CYP3A in vitro by amprenavir and ritonavir: comparison with ketoconazole. Eur J Clin Pharmacol. 2000 Jun;56(3):259-61. PMID:10952482


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