Kaletra (lopinavir/ritonavir).
OBJECTIVE
To review the pharmacology, virology, pharmacokinetics, efficacy, safety, and clinical use of lopinavir/ritonavir (Kaletra, Abbott Laboratories).


METHODS
English-language MEDLINE and AIDSline searches were performed (1966-July 2001) using lopinavir, ABT-378, and Kaletra as key words. Abstracts from infectious diseases and HIV scientific meetings were identified. Abbott Laboratories provided additional published and unpublished information.


METHODS
All publications, meeting abstracts, and unpublished information were reviewed and relevant items included. In vitro and preclinical studies were included as well as Phase II and III clinical trials.


RESULTS
Lopinavir/ritonavir is a fixed-dose protease inhibitor (PI) combination used for the treatment of HIV-1 infection. Lopinavir, the active component of this combination, is extensively metabolized by CYP3A4 and produces low systemic concentrations when used alone. Ritonavir potently inhibits CYP3A4 and is used to enhance the systemic exposure of lopinavir. This combination results in lopinavir concentrations that greatly exceed those necessary in vitro to inhibit both wild-type and PI-resistant HIV isolates. In clinical trials with antiretroviral naïve and experienced patients, lopinavir/ritonavir was effective at suppressing HIV-RNA and increasing CD4+ T cell counts. Compared with other PIs, lopinavir/ritonavir may have advantages in the areas of pharmacokinetics, efficacy, and resistance. Toxicity, drug interactions, and medication adherence are important considerations surrounding its clinical use.


CONCLUSIONS
Lopinavir/ritonavir is an effective option for the treatment of HIV-1-infected individuals when used in combination with other antiretroviral agents. It may be used as a component of initial therapy or salvage therapy; future studies will better define its place in therapy.
Corbett
Amanda H
AH
School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7360, USA.
Lim
Michael L
ML
Kashuba
Angela D M
AD
D000328:Adult; D019540:Area Under Curve; D002648:Child; D002986:Clinical Trials as Topic; D004347:Drug Interactions; D017850:Economics, Pharmaceutical; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D061466:Lopinavir; D008862:Microsomes, Liver / Q000378:metabolism; D011744:Pyrimidinones / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D014779:Virus Replication / Q000187:drug effects
D011744:Pyrimidinones; D061466:Lopinavir