Double Protease Inhibitor Lopinavir/Ritonavir Does Not Impair Drug Exposure of Saquinavir

The objective of the current study was to assess the pharmacokinetic interaction of saquinavir (Invirase) and lopinavir/ritonavir (Kaletra).  

Patients from the Frankfurt, Germany HIV cohort with limited reverse transcriptase inhibitor (RTI) options received the protease inhibitor (PI) combination of saquinavir (Invirase; soft-gel capsules) 1000 mg twice a day plus lopinavir/ritonavir (Kaletra) 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.  

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

Data were collected from 45 patients (LOPSAQ) and 32 patients (RITSAQ). There was no significant difference between the groups for median saquinavir C_min, C_max, Cl_tot 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 C_min, C_max and AUC were lower, the Cl_tot 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.  

The authors conclude, “Effective plasma levels of both saquinavir and lopinavir can be achieved by the co-administration of saquinavir soft-gel capsules [Invirase] and lopinavir/ritonavir [Kaletra].”

"This boosted double PI combination could be an effective option for patients with limited RTI options.”

03/19/04

Reference
C Stephan and others. Saquinavir drug exposure is not impaired by the boosted double protease inhibitor combination of lopinavir/ritonavir. AIDS 18(3): 503-508. February 20, 2004.