Tipranavir: A novel non-peptidic protease inhibitor for the treatment of HIV infection

Expert Opinion on Investigational Drugs

Volumn 12, Issue 11, 2003, Pages 1821-1828

  Mehandru, Saurabh ^a   Markowitz, Martin ^a  

^a ROCKEFELLER UNIVERSITY   (United States)

Author keywords

HIV; Protease inhibitor; Tipranavir

Indexed keywords

AMPRENAVIR; ANTIRETROVIRUS AGENT; ASPARTIC PROTEINASE; ATORVASTATIN; CATHEPSIN D; CATHEPSIN E; CD4 ANTIGEN; CYTOCHROME P450 3A4; DIDANOSINE; EFAVIRENZ; GAMMA GLUTAMYLTRANSFERASE; GLYCOPROTEIN P; INDINAVIR; ISOENZYME; LOPINAVIR; MEVINOLIN; NELFINAVIR; NEVIRAPINE; PEPSIN A; PRAVASTATIN; PROTEINASE INHIBITOR; RITONAVIR; RNA DIRECTED DNA POLYMERASE; RNA DIRECTED DNA POLYMERASE INHIBITOR; SAQUINAVIR; SIMVASTATIN; TENOFOVIR; TIPRANAVIR; UNINDEXED DRUG; ZIDOVUDINE;

ABDOMINAL PAIN; ANTIVIRAL ACTIVITY; ARTICLE; CLINICAL TRIAL; CROSS REACTION; DIARRHEA; DOSE RESPONSE; DRUG ABSORPTION; DRUG BIOAVAILABILITY; DRUG BLOOD LEVEL; DRUG CAPSULE; DRUG CLEARANCE; DRUG EFFICACY; DRUG FORMULATION; DRUG HALF LIFE; DRUG SAFETY; DRUG TOLERABILITY; FERTILITY; GASTROINTESTINAL TOXICITY; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS 1; HUMAN IMMUNODEFICIENCY VIRUS 2; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; NAUSEA; NONHUMAN; STEADY STATE; STRUCTURE ACTIVITY RELATION; TERATOGENICITY; VERTIGO; VIRUS ISOLATION; VIRUS LOAD; VIRUS RESISTANCE; VOMITING;

CLINICAL TRIALS; DRUG INTERACTIONS; DRUG RESISTANCE, VIRAL; HIV INFECTIONS; HIV PROTEASE INHIBITORS; HUMANS; PYRIDINES; PYRONES;

EID: 0242392037     PISSN: 13543784     EISSN: None     Source Type: Journal    
DOI: 10.1517/13543784.12.11.1821     Document Type: Article

References (39)

1. JONES JL, HANSON DL, DWORKIN MS et al.: Surveillance for AIDS-defining opportunistic illnesses, 1992-1997. MMWR CDC Surveill. Summ. (1999) 48(2):1-22.
2. RICHMAN DD: HIV drug resistance. Ann. Rev. Pharmacol. Toxicol. (1993) 33:149-164.
3. LITTLE SJ, DAAR ES, D'AQUILA RT et al.: Reduced antiretroviral drug susceptibility among patients with primary HIV infection. JAMA (1999) 282(12):1142-1149.
4. YERLY S, VORA S, RIZZARDI P et al.: Acute HIV infection: impact on the spread of HIV and transmission of drug resistance. AIDS (2001) 15(17):2287-2292.
5. BODEN D, HURLEY A, ZHANG L et al.: HIV-1 drug resistance in newly infected individuals. JAMA (1999) 282(12):1135-1141.
6. LITTLE SJ, HOLTE S, ROUTY JP et al.: Antiretroviral drug resistance among patient, recently infected with HIV. N. Engl. J. Med (2002) 347(6):385-394.
7. POPPE SM, SLADE DE, CHONG KT et al.: Antiviral activity of the dihydropyrone PNU-140690, a new nonpeptidic human immunodeficiency virus protease inhibitor. Antimicrob. Agents Chemother. (1997) 41(5):1058-1063.
8. RUSCONI S, LA SETA CATAMANCIO S, CITTERIO P et al.: Susceptibility to PNU-140690 (tipranavir) of human immunodeficiency virus Type 1 isolates derived from patients with multidrug resistance to other protease inhibitors. Antimicrob. Agents Chemother. (2000) 44(5):1328-1332.
9. LARDER BA, HERTOGS K, BLOOR S et al.: Tipranavir inhibits broadly protease inhibitor-resistant HIV-1 clinical samples. AIDS (2000) 14(13):1943-1948.
10. CURRY R, MARKOWITZ M, SLATER L et al.: Safety and efficacy of tipranavir, a non-peptidic protease inhibitor in multiple PI-Failure patients. 1st IAS Conference on HIV Pathogenesis and Treatment, Buenos Aires, Argentina (2001) (Abstract 3).
11. GATHE J, KOHLBRENNER VM, PIERONE G et al.: Tipranavir/ritonavir demonstrates potent efficacy in multiple protease inhibitor patients. 10th Conference on Retroviruses and Opportunistic Infections, Boston, MA, USA (2003) (Abstract 179).
12. CHONG KT, PAGANO PJ: In vitro combination of PNU-140690, a human immunodeficiency virus Type 1 protease inhibitor, with ritonavir against ritonavir-sensitive and -resistant clinical isolates. Antimicrob. Agents Chemother. (1997) 41(11):2367-2373.
13. DOYON L, TREMBLAY S, CARTIER M, CORDINGLEY MG: In vitro susceptibility of HIV-1 to tipranavir. 11th International HIV Drug Resistance Workshop: Basic Principles and clinical Implications, Seville, Spain (2002).
14. TURNER SR, STROHBACH JW, TOMMASI RA et al.: Tipranavir (PNU-140690): a potent, orally bioavailable nonpeptidic HIV protease inhibitor of the 5,6-diydro-4-hydroxy,2-pyrone sulfonamide class. J. Med. Chem. (1998) 41(18):3467-3476.
15. BORIN MT, WANG Y, SCHNECK DW et al.: Multiple-dose, safety, tolerance, and pharmacokinetics of the protease inhibitor PNU-140690 in healthy volunteers. 5th Conference on Retroviruses and Opportunistic Infections, Chicago, IL, USA (1998) (Abstract 648).
16. MEAL TCB, WANG Y: The safety, tolerance, pharmacokinetics and efficacy of PNU-140690, a new non-peptidic HIV protease inhibitor, in a Phase I/II study. 12th World AIDS Conference, Geneva (1998) (Abstract 41176).
17. EAGLING VA, BACK DJ, BARRY MG: Differential inhibition of cytochrome P450 isoforms by the protease inhibitors, ritonavir, saquinavir and indinavir. Br. J. Clin. Pharmacol. (1997) 44(2):190-194.
18. MOYLE GJ, BACK D: Principles and practice of HIV-protease inhibitor pharmacoenhancement. HIV Med. (2001) 2(2):105-113.
19. BALDWIN JR, BORIN MT, WANG Y, SCHNECK DW, HOPKINS NK: Effects of food and antacid on bioavailability of the protease inhibitor PNU-140690 in healthy volunteers. 5th Conference on Retroviruses and Opportunistic Infections, Chicago, IL, USA (1998) (Abstract 649).
20. MCCALLISTER S, SABO JP, MAYERS DT, GALITZ L: An open-label, steady-state investigation of the pharmacokinetics (PK) of tipranavir (TPV) and ritonavir (RTV) and their effects on cytochrome P450 (3A4) activity in normal, healthy volunteers. 9th Conference on Retroviruses and Opportunistic Infections, Seattle, WA, USA (2002)
21. BALDWIN JR, BORIN MT, FERRY JJ et al.: Phamacokinetic interaction between HIV protease inhibitors tipranavir and ritonavir 39th Interscience Conference on Antimicrobial Agents and Chemotherapy, San Francisco, CA, USA (1999) (Abstract 657).
22. ERICKSON-VIITANEN S, MANFREDI J, VIITANEN P et al.: Cleavage of HIV-1 gag polyprotein synthesized in vitro: sequential cleavage by the vital protease. AIDS Res. Hum. Retroviruses (1989) 5(6):577-591.
23. WLODAWER A, MILLER M, JASKOLSKI M et al.: Conserved folding in retroviral proteases: crystal structure of a synthetic HIV-1 protease. Science (1989) 245(4918):616-621.
24. PENG C, HO BK, CHANG TW, CHANG NT: Role of human immunodeficiency virus Type 1-specific protease in core protein maturation and viral infectivity. J. Virol. (1989) 63(6):2550-2556.
25. HATANAKA M, NAM SH: Identification of HTLV-I gag protease and its sequential processing of the gag gene product. J. Cell Biochem. (1989) 40(1):15-30.
26. THAISRIVONGS S, SKULNICK HI, TURNER SR et al.: Structure-based design of HIV protease inhibitors: sulfonamide-containing 5,6-dihydro-4-hydroxy-2-pyrones as non-peptidic inhibitors. J. Med. Chem. (1996) 39(22):4349-4353.
27. JAPOUR AJ, MAYERS DL, JOHNSON VA et al.: Standardized peripheral blood mononuclear cell culture assay for determination of drug susceptibilities of clinical human immunodeficiency virus Type 1 isolates. The RV-43 Study Group, the AIDS Clinical Trials Group Virology Committee Resistance Working Group. Antimicrob. Agents Chemother. (1993) 37(5):1095-1101.
28. DOYON L, TREMBLAY S, WARDROP E et al.: Characterization of HIV-1 showing decreased susceptibility to tipranavir and their inhibition by tipranavir-containing drug mixtures XII International HIV Drug Resistance Workshop. Los Cabos, Mexico (2003) (Abstract 14).
29. WANG Y, DAENZER CL, WOOD R et al.: The safety, efficacy and viral dynamics analysis of tipranavir, a new generation protease inhibitor, in a Phase II study in antiretroviral naive HIV-1 infected patients. 7th Conference on Retroviruses and Opportunistic Infections, San Francisco, CA, USA (2000) (Abstract 673).
30. McCALLISTER S, NEUBACHER D, VERBIEST W, MAYERS DL: Susceptibility profile of tipranavir at baseline and subsequent virologic response in a cohort of patients with multiple-PI failure. XI International HIV Drug Resistance Workshop, Seville Spain (2002).
31. HALL D, McCALLISTER S, NEUBACHER D, KRAFT M, MAYERS DL: Characterization of treatment-emergent resistance mutations in two phase-II studies of tipranavir. XII International HIV Drug Resistance Workshop, Los Cabos, Mexico (2003) (Abstract 13).
32. JAYAWEERA DT, SLATER L, HAAS D et al.: Susceptibility profile of tipranavir at baseline and subsequent virological response in a cohort of patients with single-protease inhibitor failure. 2nd International HIV Workshop on Management of Treatment-Experienced Patients, San Diego, CA, USA (2002) (Abstract P5).
33. SLATER L, FARTHING C, JAYAWEERA J: Safety and efficacy of tipranavir (TPV), a novel non-peptidic protease inhibitor, plus ritonavir (RTV), in PI-failure patients. 41st Interscience Conference on Antimicrobial Agents and Chemotherapy, Chicago, IL, USA (2001) (Abstract LB-15).
34. SQUIRES K, McCALIISTER S, LAZZARIN A et al.: Tipranavir/ritonavir (TPV/r) demonstrates a uniquely robust resistance profile in multiple-protease inhibitor (PI)-experienced patients: correlation of baseline genotype and antiviral activity in BI 1182.52.2nd IAS Conference on HIV Pathogenesis and Treatment, Paris (2003) (Abstract 812).
35. YENI P, McGREGOR T, GATHE J et al.: Correlation of viral load reduction and plasma levels in multiple protease inhibitor (PI)-experienced patients taking tipranavir ritonavir (TPV/r) in a Phase IIB trial. 10th Conference on Retroviruses and Opportunistic Infections, Boston, MA, USA (2003) (Abstract 528).
36. COOPER D, HALL D, JAYAWEERA D et al.: Baseline phenotypic susceptibility to tipranavir/ritonavir (TPV/r) is retained in isolates from patients with multiple-protease inhibitor (PI) experience. 10th Conference on Retroviruses and Opportunistic Infections, Boston, MA. USA (2003) (Abstract: 596).
37. MAYERS DL, KOHLBRENNER VM, DOHNANYI C et al.: The Inhibitory Quotient (IQ) of Tipranavir/Ritonavir (TPR/r) in triple class experienced HIV+ patients; results from BI 1182.52. 2nd MS Conference on HIV Pathogenesis and Treatment, Paris (2003) (Abstract 9).
38. SABO J, MacGREGOR T, LAMSON M: Pharmacokinetics of tipranavir and nevirapine. Can. J. Infect. Dis. (2001) 12(Suppl. B):40.
39. ROZKO PJ, CURRY R, BRAZINA B et al.: Standard doses of efavirenz (EFV), ziduvudine (ZDV), tenofovir (TDF) and didanosine (ddI) may be given with tipranavir/ritonavir (TPV/r). 2nd IAS Conference on HIV Pathogenesis and Treatment, Paris (2003) (Abstract 865).