Once-daily treatment with saquinavir mesylate (2000 mg) and ritonavir (100 mg) together with a fixed-dose combination of abacavir/lamivudine (600/300 mg) or tenofovir/emtricitabine (245/200 mg) in HIV-1-infected patients.
OBJECTIVE
To investigate the feasibility and pharmacokinetics of a once-daily regimen of 2000 mg saquinavir mesylate boosted with 100 mg ritonavir.


METHODS
Patients successfully treated with 1000 mg saquinavir boosted with 100 mg ritonavir twice daily together with two nucleoside or nucleotide reverse transcriptase inhibitors [N(t)RTIs] who were switched to 2000 mg saquinavir with 100 mg ritonavir once daily with unchanged N(t)RTI therapy were analysed. CD4 cells, HIV-RNA PCR and metabolic parameters were compared between baseline and 3, 6, 9 and 12 months after the switch. Saquinavir and ritonavir drug levels were measured before and a median of 3 weeks after switching from twice to once daily at 0, 1, 2, 4, 6, 9, 12 and 24 h after intake of the medication. The area under the serum concentration-time curve from 0 to 24 h (AUC(0-24)) was calculated using the trapezoidal rule.


RESULTS
Eighteen patients (16 males, median age of 41 years) with a median CD4 cell count of 464 cells/mm(3) were analysed. HIV-RNA PCR remained <500 copies/mL for all patients. After switching from 100 mg twice daily to 100 mg once daily, the AUC(0-24) for ritonavir decreased significantly [21 874 to 10 267 ng.h/mL, geometric mean ratio (GMR) = 0.47; P < 0.001], whereas the AUC(0-24) for saquinavir decreased only marginally from 35 000 to 34 490 ng.h/mL (GMR = 0.99; P = 0.426). The CD4 cell count and the fasting metabolic parameters remained unchanged.


CONCLUSIONS
Once-daily treatment with ritonavir-boosted saquinavir was well tolerated and resulted in similar saquinavir drug exposure despite much lower ritonavir concentrations when compared with a twice-daily dosing schedule.
HIVCENTER, JW Goethe University Hospital, Theodor Stern Kai 7, Frankfurt, Germany. markusbickel@hotmail.com
M
M
Bickel
A
A
Bodtländer
G K
GK
Knecht
C
C
Stephan
N
N
von Hentig
M
M
Kurowski
P
P
Gute
S
S
Klauke
T
T
Lutz
D000225:Adenine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods; D019540:Area Under Curve; D018791:CD4 Lymphocyte Count; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D015224:Dideoxynucleosides; D004338:Drug Combinations; D000068679:Emtricitabine; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1 / Q000302:isolation & purification; D006801:Humans; D019259:Lamivudine / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D063065:Organophosphonates / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D010949:Plasma / Q000737:chemistry; D012367:RNA, Viral / Q000097:blood; D019438:Ritonavir / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D019258:Saquinavir / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D000068698:Tenofovir; D016896:Treatment Outcome; D019562:Viral Load; D000099227:Abacavir
D000225:Adenine; D019380:Anti-HIV Agents; D003841:Deoxycytidine; D015224:Dideoxynucleosides; D004338:Drug Combinations; D000068679:Emtricitabine; D019259:Lamivudine; D063065:Organophosphonates; D012367:RNA, Viral; D019438:Ritonavir; D019258:Saquinavir; D000068698:Tenofovir; C492871:abacavir, lamivudine drug combination; D000099227:Abacavir