Steady-state amprenavir, tenofovir, and emtricitabine pharmacokinetics before and after reducing ritonavir boosting of a fosamprenavir/tenofovir/emtricitabine regimen from 200 mg to 100 mg once daily (TELEX II).
OBJECTIVE
Evaluate how reducing ritonavir (RTV) boosting from 200 mg to 100 mg once daily (QD) affects steady-state pharmacokinetics of components of a fosamprenavir (FPV)-based regimen.


METHODS
Prospective, open-label, pharmacokinetic study in 12 HIV-infected patients stabilized on FPV/RTV 1400 mg/200 mg + tenofovir disoproxil fumarate (TDF)/emtricitabine (FTC) 300 mg/200 mg QD (TELEX II). Pharmacokinetics were assessed by noncompartmental analysis at baseline and 4 weeks after RTV reduction to 100 mg QD.


RESULTS
Baseline median minimum plasma concentration (Cmin) and area under the plasma concentration-time curve over 24 hours post dose (AUC24h) were as follows: APV: 1,708 ng/mL, 84,260 h * ng/mL; tenofovir: 53 ng/mL, 2,420 h * ng/mL; FTC: 58 ng/mL, 9,190 h * ng/mL; RTV: 80 ng/mL, 10,230 h * ng/mL. Four weeks after reducing RTV, changes in Cmin and AUC24h were: APV: +26%, +0.6%; tenofovir: +77%, +30%; FTC: +188%, +13%; RTV -64%, -79%. Component plasma concentration ranges were consistent with historical values. Median APV Cmin was 14.7-fold above the protein-binding-adjusted 50% inhibitory concentration of wild-type HIV. Four weeks after RTV reduction, HIV-1 RNA levels remained <50 copies/mL in all patients, median CD4+ count increased from 465 to 495 cells/mm3, and favorable lipid changes and no adverse events were observed.


CONCLUSIONS
Reducing RTV boosting from 200 to 100 mg QD of FPV/TDF/FTC QD conferred no detrimental effect on APV, tenofovir, FTC, or RTV pharmacokinetics and maintained virologic suppression.
Parks
David A
DA
CentralWest Research, St. Louis, Missouri, USA. gr8docs@aol.com
Jennings
H Clay
HC
Taylor
Christopher
C
Pakes
Gary E
GE
Acosta
Edward P
EP
D000225:Adenine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000493:pharmacokinetics; D000998:Antiviral Agents / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics* / Q000592:standards; D018791:CD4 Lymphocyte Count; D002219:Carbamates / Q000008:administration & dosage / Q000493:pharmacokinetics; D002851:Chromatography, High Pressure Liquid; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D004338:Drug Combinations; D000068679:Emtricitabine; D005260:Female; D005663:Furans; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy*; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010755:Organophosphates / Q000008:administration & dosage / Q000493:pharmacokinetics; D063065:Organophosphonates / Q000008:administration & dosage / Q000493:pharmacokinetics; D011446:Prospective Studies; D012367:RNA, Viral; D019438:Ritonavir / Q000008:administration & dosage / Q000493:pharmacokinetics; D013449:Sulfonamides / Q000008:administration & dosage / Q000493:pharmacokinetics; D000068698:Tenofovir; D019562:Viral Load
D019380:Anti-HIV Agents; D000998:Antiviral Agents; D002219:Carbamates; D004338:Drug Combinations; D005663:Furans; D010755:Organophosphates; D063065:Organophosphonates; D012367:RNA, Viral; D013449:Sulfonamides; D003841:Deoxycytidine; C095108:amprenavir; D000068698:Tenofovir; D000068679:Emtricitabine; D000225:Adenine; D019438:Ritonavir; C426859:fosamprenavir