Saquinavir drug exposure is not impaired by the boosted double protease inhibitor combination of lopinavir/ritonavir.
OBJECTIVE
To assess the pharmacokinetic interaction of saquinavir and lopinavir/ritonavir.


METHODS
Patients from the Frankfurt HIV cohort with limited reverse transcriptase inhibitor (RTI) options received the protease inhibitor (PI) combination of saquinavir (soft-gel capsules, 1000 mg twice a day) plus lopinavir/ritonavir (400/100 mg twice a day), without RTI (LOPSAQ group). A control group received the same doses of saquinavir and ritonavir plus two to three RTI (RITSAQ group). A steady-state 12 h pharmacokinetic assessment was performed.


METHODS
Plasma levels of saquinavir, ritonavir and lopinavir were determined by liquid chromatography-tandem mass spectrophotometry. Minimum and maximum plasma concentrations (Cmin and Cmax), the clearance (Cltot) and the area under the concentration time curve (AUC) were calculated.


RESULTS
Data were collected from 45 patients (LOPSAQ) and 32 patients (RITSAQ). There was no significant difference between the groups for median saquinavir Cmin, Cmax, Cltot and AUC (LOPSAQ: 543 ng/ml, 2300 ng/ml, 1020 ml/min and 16 977 ng*h/ml; RITSAQ: 427 ng/ml, 2410 ng/ml, 1105 ml/min and 15 130 ng*h/ml). Median ritonavir Cmin, Cmax and AUC were lower, the Cltot was higher in the LOPSAQ group (78 ng/ml, 428 ng/ml and 2972 ng*h/ml, 551 ml/min) compared with RITSAQ (194 ng/ml, 683 ng/ml and 6506 ng*h/ml, 266 ml/min; P < 0.001). Lopinavir levels were similar to historical data.


CONCLUSIONS
Effective plasma levels of both saquinavir and lopinavir can be achieved by the co-administration of saquinavir soft-gel capsules and lopinavir/ritonavir. This boosted double PI combination could be an effective option for patients with limited RTI options.
Stephan
Christoph
C
Division of Infectious Disease, and Institute of Clinical Pharmacology, Pharma Center, JW Goethe University Hospital, Frankfurt, Germany. stephanc@hivcenter.de
von Hentig
Nils
N
Kourbeti
Irene
I
Dauer
Brenda
B
Mösch
Manfred
M
Lutz
Thomas
T
Klauke
Stephan
S
Harder
Sebastian
S
Kurowski
Michael
M
Staszewski
Schlomo
S
D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D002214:Capsules; D015331:Cohort Studies; D004338:Drug Combinations; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000097:blood* / Q000188:drug therapy / Q000821:virology; D017320:HIV Protease Inhibitors / Q000097:blood*; D015497:HIV-1; D006801:Humans; D061466:Lopinavir; D008297:Male; D008875:Middle Aged; D011744:Pyrimidinones / Q000097:blood; D019438:Ritonavir / Q000097:blood; D019258:Saquinavir / Q000097:blood*; D019562:Viral Load
D002214:Capsules; D004338:Drug Combinations; D017320:HIV Protease Inhibitors; D011744:Pyrimidinones; D061466:Lopinavir; D019258:Saquinavir; D019438:Ritonavir