934
Differences in Lopinavir Plasma Concentrations Comparing Kaletra Film Coated Tablets and Soft Gelatin Capsules Translate into Distinct Lipid Abnormalities
Judit Morello*, S Rodriguez-Novoa, F Blanco, A Rubio, I Jimenez-Nacher, and V Soriano
Hosp Carlos III, Madrid, Spain
Background: A new formulation of lopinavir/ritonavir (LPV/r) as film-coated
tablets has recently replaced the formulation of LPV/r soft gelatin capsules.
Although the new formulation may show several advantages—such as no food
requirements, reduced pill count, and no refrigeration required—few data are
available about the bioequivalence of the 2 formulations, specially regarding
effects on lipids.
Methods: All
HIV patients at our institution, who had been treated with LPV/r capsules for
at least 6 months and switched in 2007 to the newer LPV/r tablets, were
retrospectively analyzed. Lipid values and LPV plasma trough concentrations
were examined before switching and 12 weeks thereafter. LPV plasma
concentrations were measured by a validated high-performance liquid
chromatography with ultraviolet detector (HPLC-UV) method. Patients taking
lipid-lowering agents were excluded from this analysis.
Results: A
total of 40 patients were identified (83% male; median age, 44 years old [IQR
41 to 48], 95.1% Caucasian). LPV plasma trough concentrations were
significantly higher with LPV/r tablets than with the old LPV/r capsules. No
significant differences were seen for total cholesterol and LDL cholesterol
when comparing both LPV/r formulations. In contrast, triglycerides were
significantly increased and HDL cholesterol reduced with LPV/r tablets compared
to capsules. The ratio of total cholesterol (TC) to HDL cholesterol was
significantly higher with tablets than capsules.
|
|
Capsules
|
Tablets
|
p
|
|
LPV plasma levels (mg/mL)
|
3.2, 2.3 to 5.2
|
4, 3.2 to 5.7
|
0.008
|
|
TC (mg/dL)
|
189, 162.7 to 219.2
|
193.5, 153.7 to 219.2
|
0.889
|
|
LDL (mg/dL)
|
121.6, 95.4 to 133.8
|
110.1, 82.3 to 141.4
|
0.512
|
|
HDL (mg/dL)
|
42.5, 33.5 to 57.5
|
39, 32 to 53
|
0.008
|
|
TC:HDL ratio
|
4.4, 3.3 to 5.2
|
4.7, 3.7 to 5.5
|
0.014
|
|
Triglycerides (mg/dL)
|
110, 84.2 to 145.2
|
147, 99 to 207
|
0.016
|
Conclusions: Higher LPV plasma trough concentrations with the new formulation of
LPV/r tablets compared with the old capsules are associated with increases in
triglycerides and reductions in the TC:HDL ratio, which may be relevant in
patients with cardiovascular risk.
|