8th Conference on Retroviruses and Opportunistic Infections


Chicago, IL - February 4 - 8, 2001



Amprenavir (APV) and ritonavir (RTV): intraindividual comparison of different doses and influence of concomitant NNRTI on steady-state pharmakokinetics in HIV-infected patients

Conf Retroviruses Opportunistic Infect 2001 Feb 4-8; 8:267 (abstract no. 739)

Degen O, Kurowski M, Van Lunzen J, Schewe CK, Stellbrink HJ;
Univ Hosp Eppendorf, Hamburg.

BACKGROUND: RTV is known to increase APV drug levels. An optimum dose of both drugs in combination remains to be defined.

METHODS: Steady-state PK of 450 mg APV and 200 mg RTV BID in 17 HIV-infected patients using liquid chromatography/mass spectometry (LC-MS). All received concomitant RTI treatment, 10 had additionally efavirenz (EFV), 2 also had nevirapine (NVP) and 5 had no NNRTI. In 5 of the NNRTI-treated patients, intraindividual comparisons of steady-state PK to 600 mg APV and 100 mg RTV BID were performed.

RESULTS: Steady-state PK of APV 45 0mg and RTV 200 mg BID after median 5 weeks of treatment (range 4-13). All had high and sustained plasma levels of APV. Without NNRTI the median Cmin was 2094 ng/ml (range 1178-2049), median Cmax was 6380 ng/ml (range 4265-14,399), and median AUC(0-8) was 29888 ng/ml (range 20254-50651). Medians with EFV were Cmin 2366 ng/ml (range 950-8183), Cmax 9076 ng/ml (range 4473-22746), and AUC(0-8) 32314 ng/ml (range 16,990-103,234). The two NVP pts. showed median Cmins of 1101 and 1536 ng/ml, median Cmaxs of 11,983 and 5773 ng/ml, and median AUC(0-8)s of 56,445 and 21,229 ng/ml. In 5 pts. (4 EFV, 1 NVP) dose was changed to 600 mg APV and 100 mg RTV BID after median 34 weeks (range 24--48). Steady-state PK median was 28 days after switch (range 21-56). Cmin decreased by 80% to a median of 469 ng/ml (range 169-2030), Cmax by 80% to a median of 1781 ng/ml (range 721-3899), and AUC(0- 8) by 77% to a median of 7869 ng/ml (range 3610-19,840).

CONCLUSIONS: 450 mg APV and 200 mg RTV BID shows high and stable plasma levels with or without concomitant NNRTI. The lowest Cmin of 950 ng/ml was >3 times above the Cmin observed at the standard dose of 1200 mg BID (320 ng/ml). The intraindividual comparison to 600 mg APV and 100 mg RTV BID shows a decrease of APV plasma level by -80% of Cmin, -80% of Cmax and -77% of AUC(0-8). Especially in salvage patients, high plasma levels may be required for optimal virological response; 450 mg APV with 200 mg RTV BID ensures a higher drug exposure in combination with NNRTIs.

2001-02-04
739

Copyright © 2001 - Foundation for Retrovirology and Human Health. Reproduction of this abstract (other than one copy for personal reference) must be cleared through the Foundation for Retrovirology and Human Health. Licensed (AIDSLINE) from National Library of Medicine.