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Pharmacokinetics Study Suggests No Problems in Combining Lopinavir and Atazanavir: Presented at CROI

By Ed Susman

DENVER, CO -- February 10, 2006 -- Researchers, looking toward possible combination therapies for treating individuals with HIV say pharmacokinetics studies found no problems when the protease inhibitors atazanavir and lopinavir are combined in the same patient.

"The combination of lopinavir/ritonavir and atazanavir with nucleoside reverse transcriptase inhibitors may be used as a salvage regimen," said Paul Pham, PharmD, a research associate in medicine at the Johns Hopkins School of Medicine, Baltimore, Maryland.

He presented his poster here on February 6^th at the 13^th Conference on Retroviruses and Opportunistic Infections (CROI).

Atazanavir, lopinavir, and ritonavir all tend to inhibit the same metabolic pathway. All 3 of the drugs utilize the CYP34A substrate.

"Previous observational studies suggest that the 2 protease inhibitors may be coadministered without significant adverse pharmacokinetic interactions," he said. "However, a formal drug interaction study has not been conducted."

Dr. Pham and colleagues conducted an open-label, multidose study to evaluate plasma levels of lopinavir and atazanavir. To elucidate how the 2 drugs would interact within the body, the researchers conducted a series of tests on 14 healthy men and 1 woman.

In period 1 (days 1-10), atazanavir/ritonavir 300/100 mg was administered once daily. In period 2 (days 11-24), atazanavir 300 mg was delivered once daily and lopinavir/ritonavir 400/100mg was given twice daily. In period 3 (days 25-34), atazanavir/ritonavir 300/100mg was given once daily and lopinavir/ritonavir 400/100mg was given twice daily.

Blood samples were collected for up to 24 hours after dosing on days 10, 24, and 34.

The minimal trough levels for both atazanavir and lopinavir were increased significantly in the study population when the 2 drugs were used together, Dr. Pham said. He estimated that the minimum trough levels of atazanavir increased by 45% (P = .006) when compared with atazanavir alone. The trough levels increased by 64% (P = .0002) when both drugs were boosted by ritonavir and were compared with atazanavir alone.

"The combination of atazanavir 300 mg once daily plus lopinavir/ritonavir 400/100 mg twice daily was well tolerated and resulted in favorable pharmacokinetic profiles for both atazanavir and lopinavir," Dr. Pham said.

He suggested that the combination can be further evaluated in treatment-experienced patients requiring a dual boosted protease inhibitor-containing regimen.

The research was sponsored by Bristol-Myers Squibb.


[Presentation title: Beneficial Pharmacokinetic Interaction Between Atazanavir and Lopinavir/Ritonavir. Abstract 585]

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