Amprenavir and Lopinavir Pharmacokinetics following Coadministration of Amprenavir or Fosamprenavir with Lopinavir/Ritonavir, with or without Efavirenz

Autor:	Patricia Barditch-Crovo, Christine Radebaugh, Wasif A. Khan, Paul A. Pham, Charles Flexner, Teresa L. Parsons, Kathryn A. Carson, Michelle Parish, Roula B Qaqish, Craig W. Hendrix, Gary E Pakes
Rok vydání:	2007
Předmět:	Pharmacology Efavirenz Reverse-transcriptase inhibitor Lopinavir/ritonavir Lopinavir Fosamprenavir chemistry.chemical_compound Amprenavir Infectious Diseases Pharmacokinetics chemistry medicine Pharmacology (medical) Ritonavir medicine.drug
Zdroj:	Antiviral Therapy. 12:963-970
ISSN:	2040-2058 1359-6535
DOI:	10.1177/135965350701200614
Popis:	Background Amprenavir (APV), fosamprenavir (FPV), lopinavir (LPV), ritonavir (RTV) and efavirenz (EFV) are to varying degrees substrates, inducers and inhibitors of CYP3A4. Coadministration of these drugs might result in complex pharmacokinetic drug-drug interactions. Methods Two prospective, open-label, non-randomized studies evaluated APV and LPV steady-state pharmacokinetics in HIV-infected patients on APV 750 mg twice daily + LPV/RTV 533/133 mg twice daily with EFV ( n=7) or without EFV ( n=12) + background nucleosides (Study 1) and after switching FPV 1,400 mg twice daily for APV ( n=10) (Study 2). Results In Study 1 EFV and non-EFV groups did not differ in APV minimum plasma concentration (Cmin; 1.10 versus 1.06μg/ml, P=0.89), area under the concentration-time curve (AUC; 17.46 versus 24.34μg•h/ml, P=0.22) or maximum concentration (Cmax; 2.61 versus 4.33 μg/ml, P=0.08); for LPV there was no difference in Cmin (median: 3.66 versus 6.18μg/ml, P=0.20), AUC (81.84 versus 93.75 μg•h/ml, P=0.37) or Cmax (10.36 versus 10.93 μg/ml, P=0.61). In Study 2, after switching from APV to FPV, APV Cmin increased by 58% (0.83 versus 1.30 μg/ml, P=0.0001), AUC by 76% (19.41 versus 34.24 μg•h/ml, P=0.0001), and Cmax by 75% (3.50 versus 6.14, P=0.001). Compared with historical controls, LPV and RTV pharmacokinetics were not changed. All treatment regimens were well tolerated. Seven of eight completers (88%) maintained HIV-1 RNA Conclusions EFV did not appear to significantly alter APV and LPV pharmacokinetic parameters in HIV-infected patients taking APV 750 mg twice daily + LPV 533/133 mg twice daily. Switching FPV 1,400 mg twice daily for APV 750 mg twice daily resulted in an increase in APV Cmin, AUC, and Cmax without changing LPV or RTV pharmacokinetics or overall tolerability.
Databáze:	OpenAIRE
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