Gastric Bypass Surgery and Serum Concentrations of Zidovudine, Lamivudine, and Nelfinavir
BACKGROUND: An HIV-infected woman on zidovudine (ZDV), lamivudine (3TC), and nelfinavir (NFV) underwent Roux y gastric bypass surgery (GB) that decreased her functional gastric volume to 15 ml and bypassed 150 cm of proximal jejunum. We measured serum concentrations of ZDV, 3TC, NFV, and its active metabolite M8 prior to and at various time points following GB. METHODS: Blood was collected 30 minutes prior to and 30-, 90-, 240-, 480-minutes following the intake of ZDV, 3TC and NFV on the day prior to (T0) and on days 1-2 (T1), 7-8 (T2), 14 (T3), and 180 (T4) post-GB. Antiretroviral concentrations were measured by high performance liquid chromatography analysis on reverse phase with UV detection and expressed as mean or absolute values in mcg/ml. RESULTS: Following GB, the peak (T0 = 5.6; T1 = 0.8; T2 = 0.6; T3 = 1.0) and trough (T0 = 2.6; T1 = 0.4; T2 = 0.3; T3 = 0.4) NFV concentrations were reduced and the time to peak levels was delayed (T0 = 1:58; T1 = 2:30; T2 = 4:02; T3 = 3:50). Peak level of M8 was reduced from 0.31 to undetectable levels. Despite weight reduction of 100 pounds, peak (1.2 mcg/ml) and trough (0.4 mcg/ml) NFV concentrations remained below the reference range at 180 days post-GB. Concentrations of ZDV (peak 0.4 mcg/ml; trough 0.02 mcg/ml) and 3TC (peak 1.1 mcg/ml; trough 0.3 mcg/ml) were below the reference range pre-GB, and were not significantly affected post-GB. However, the time to peak concentration of ZDV was reduced (1:58 vs 1:13). The patient had CD4 519/µl and HIV RNA < 50-copies/ml 6 months post-GB. CONCLUSIONS: GB decreased the serum concentrations of NFV and M8 but not ZDV or 3TC. Antiretroviral pharmacokinetics is complex and requires further investigation.
R R Razonable1, L Estes1, M McMahon1, G Thompson1, T Moyer1, C V Fletcher2, J Henely1, Z Temesgen1
1Mayo Clinic, Rochester, United States; 2University of Minnesota, Minneapolis, United States