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 [9][10]
Inhibitor/Mutation Site L10 I13 G16 K20 L24 D30 V32 L33 E34 E35 M36 K43 M46 I47 G48 I50 F53 I54 D60 I62 L63 I64 H69 A71 G73 T74 L76 V77 V82 N83 I84 I85 N88 L89 L90 I93
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
  9. ↑ Poveda E, de Mendoza C, Martin-Carbonero L, Corral A, Briz V, Gonzalez-Lahoz J, Soriano V. Prevalence of darunavir resistance mutations in HIV-1-infected patients failing other protease inhibitors. J Antimicrob Chemother. 2007 Oct;60(4):885-8. Epub 2007 Jul 23. PMID:17646201 doi:10.1093/jac/dkm276
  10. ↑ Johnson VA, Brun-Vezinet F, Clotet B, Gunthard HF, Kuritzkes DR, Pillay D, Schapiro JM, Richman DD. Update of the drug resistance mutations in HIV-1: December 2009. Top HIV Med. 2009 Dec;17(5):138-45. PMID:20068260


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