TY - BOOK AU - Stoher, W. AU - Back, D. AU - Dunn, D. AU - Sabin, C. AU - Winston, A. AU - Gilson, R. AU - Pillay, D. AU - Hill, T. AU - Ainsworth, J. AU - Pozniak, A. AU - Leen, C. AU - Bansi, L. AU - Fisher, M. AU - Orkin, C. AU - Anderson, J. AU - Johnson, M. AU - Easterbrook, P. AU - Gibbons, S. AU - Khoo, S. ED - UK CHIC Study ED - Liverpool TDM Database TI - Factors influencing efavirenz and nevirapine plasma concentration: effect of ethnicity, weight and co-medication SN - 13596535 PY - 2008/// N1 - NMUH Staff Publications; 13 N2 - <div><h4>BACKGROUND: </h4><p>The aim of this study was to examine <span class="highlight" style="background-color:">factors</span> <span class="highlight" style="background-color:">influencing</span> <span class="highlight" style="background-color:">plasma</span> <span class="highlight" style="background-color:">concentration</span> of <span class="highlight" style="background-color:">efavirenz</span> and <span class="highlight" style="background-color:">nevirapine</span>.</p><h4>METHODS: </h4><p>Data from the Liverpool Therapeutic Drug Monitoring (TDM) registry were linked with the UK Collaborative HIV Cohort (CHIC) Study. For each patient, the first measurement of <span class="highlight" style="background-color:">efavirenz</span> (600 or 800 mg/day) or <span class="highlight" style="background-color:">nevirapine</span> (400 mg/day) <span class="highlight" style="background-color:">plasma</span> <span class="highlight" style="background-color:">concentration</span> was included. Linear regression was used to evaluate the association of dose, gender, age, <span class="highlight" style="background-color:">weight</span>, <span class="highlight" style="background-color:">ethnicity</span> and concomitant antiretroviral drugs or rifampicin with log-transformed drug <span class="highlight" style="background-color:">concentration</span>, adjusted for time since last intake.</p><h4>RESULTS: </h4><p>Data from 339 patients on <span class="highlight" style="background-color:">efavirenz</span> (34% black, 17% rifampicin) and 179 on <span class="highlight" style="background-color:">nevirapine</span> (27% black, 6% rifampicin) were included. Multivariable models revealed the following predictors for <span class="highlight" style="background-color:">efavirenz</span> <span class="highlight" style="background-color:">concentration</span>: black <span class="highlight" style="background-color:">ethnicity</span> (59% higher; P&lt;0.001), <span class="highlight" style="background-color:">weight</span> (10% lower per additional 10 kg; P=0.002), 800 mg/day (52% higher; P=0.027), rifampicin (35% lower; P=0.039), and zidovudine (25% lower; P=0.010). Notably, without adjustment for other <span class="highlight" style="background-color:">factors</span>, patients on rifampicin had 48% higher <span class="highlight" style="background-color:">efavirenz</span> <span class="highlight" style="background-color:">concentration</span>, as these patients were mostly black and on 800 mg/day. For <span class="highlight" style="background-color:">nevirapine</span> the predictors were black <span class="highlight" style="background-color:">ethnicity</span> (39% higher; P=0.002), rifampicin (40% lower; P=0.002), protease inhibitor (28% higher; P=0.008) and tenofovir (22% higher; P=0.024).</p><h4>CONCLUSIONS: </h4><p>We observed clear associations between <span class="highlight" style="background-color:">ethnicity</span> and concentrations of <span class="highlight" style="background-color:">nevirapine</span> and <span class="highlight" style="background-color:">efavirenz</span>. Our analyses confirm that concomitant rifampicin substantially decreases <span class="highlight" style="background-color:">concentration</span> of both <span class="highlight" style="background-color:">efavirenz</span> and <span class="highlight" style="background-color:">nevirapine</span>; however, for <span class="highlight" style="background-color:">efavirenz</span> this <span class="highlight" style="background-color:">effect</span> was more than counterbalanced by the <span class="highlight" style="background-color:">effect</span> of <span class="highlight" style="background-color:">ethnicity</span> and increased <span class="highlight" style="background-color:">efavirenz</span> dose. There was also an additional impact of <span class="highlight" style="background-color:">weight</span>, which should be considered when determining optimal dosage. Other associations from our analysis (between tenofovir or protease inhibitor and <span class="highlight" style="background-color:">nevirapine</span>, and zidovudine and <span class="highlight" style="background-color:">efavirenz</span>), require confirmation in formal pharmacokinetic studies.</p></div> UR - http://www.ncbi.nlm.nih.gov/pubmed/18771051 UR - http://ferriman.wufoo.com/forms/r7x3a7/ ER -