{"id":7357,"date":"2005-05-15T18:41:58","date_gmt":"2005-05-15T17:41:58","guid":{"rendered":"http:\/\/moomango.co.uk\/htb\/?p=7357"},"modified":"2014-05-21T18:09:46","modified_gmt":"2014-05-21T18:09:46","slug":"paediatric-dose-finding-atazanavir-and-atazanavirritonavir","status":"publish","type":"post","link":"https:\/\/i-base.info\/htb\/7357","title":{"rendered":"Paediatric dose finding atazanavir and atazanavir\/ritonavir"},"content":{"rendered":"<p><strong>Polly Clayden, HIV i-Base<\/strong><\/p>\n<p><strong>Jennifer Kiser and colleagues reported findings from PACTG 1020, a prospective phase I\/II open-label area-under the concentration time curve (AUC)-controlled study to determine the safety, pharmacokinetics, and optimal dose of once-daily atazanavir (ATV) powder and capsules with and without ritonavir (RTV) in HIV-positive children in combination with two nucleosides.<\/strong><\/p>\n<p>ART-na\u00efve and -experienced children with viral load &gt; 5000 copies\/mL and ATV phenotypic susceptibility (&lt; 10-fold wild type IC50) were eligible for this study.<\/p>\n<p>There are 8 study groups in PACTG 1020: groups 1 to 4 evaluating unboosted and in groups 5 to 8 boosted ATV. This poster reported preliminary PK data from 23 children in groups 5-8 receive RTV boosted ATV at a dose of 310mg\/m<sup>2<\/sup>.<\/p>\n<p>Intensive PK studies were performed on day 7 and at week 56, plus 14 days after dose adjustment. A new ATV dose is calculated for children with: an AUC &lt;30\u00b5g*hr\/mL or AUC &gt;90\u00b5g*hr\/mL, increases of 25% in weight.<\/p>\n<p>The authors reported week 1 pharmacokinetic results for 23 children ages 0.3-19.6 years. Overall median AUC and oral clearance (CL\/F) were 60.8\u00b5g*hr\/mL and 4.7L\/hr\/m<sup>2<\/sup> respectively.<\/p>\n<p>In the youngest group (group 5, median age 1.0 [range 0.3-1.3] years, n = 6), median AUC and oral clearance (CL\/F) were 53.6 (range 7.3-110) mcg\u2022hr\/mL and 8.1 (range 2.5-36) L\/hr\/m<sup>2<\/sup> in children receiving powder at a dose of 125 (range 50-150)mg \/298 (range182-367)mg\/m<sup>2<\/sup>.<\/p>\n<p>In older children receiving powder (group 6, median age 4.1 [range 2.6-12] years, n = 7), the median AUC and CL\/F were 50.3 mcg\u2022hr\/mL and 6.2 L\/hr\/m<sup>2<\/sup> at a dose of 200 (range 150-500) mg\/312 (range 268-327) mg\/m<sup>2<\/sup>. Older children receiving capsules (group 7, median age 10.5 [range 8.7-11.5], n=5) the median AUC and CL\/F were 73.8 (range 60-134.2) mcg\u2022hr\/mL and 4.2 (range 2.2-4.7) L\/hr\/m<sup>2<\/sup> at a dose of 400 (range 300-500) mg\/286 (range 274-349) mg\/m<sup>2<\/sup>.<\/p>\n<p>In the oldest group of children receiving capsules (group 8, median age 17.7 [range 13.1-19.6], n=5) the median AUC and CL\/F were 62.4 (range 51.5-84.7) mcg\u2022hr\/mL and 4.5 (range 3.4-6.0) L\/hr\/m2 at a dose of 500 (range 400-600) mg\/286 (range 281-311) mg\/m<sup>2<\/sup>.<\/p>\n<p>The authors concluded: \u201cThe median ATV AUC and CL\/F in adults receiving ATV\/RTV 300\/100mg once daily are 53.8 \u00b5g\u2022hr\/mL and 3.2 L\/hr\/m<sup>2<\/sup> respectively. Thus ATV CL\/F is age-dependent and faster in children than in adults, as seen with other protease inhibitors.<\/p>\n<p>\u201cAs expected, the addition of RTV decreases the clearance and increases the AUC of ATV in children.\u201d<\/p>\n<p>These data are preliminary and the optimal dose of ATV\/RTV has not yet been established. The authors added: \u201cFurther evaluations are underway in P1020 to establish the optimal dose of ATV\/RTV in subjects 91 days to 21 years in the United States and South Africa.\u201d<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Polly Clayden, HIV i-Base Jennifer Kiser and colleagues reported findings from PACTG 1020, a prospective phase I\/II open-label area-under the concentration time curve (AUC)-controlled study to determine the safety, pharmacokinetics, and optimal dose of once-daily atazanavir (ATV) powder and capsules &hellip;<\/p>\n","protected":false},"author":4,"featured_media":0,"comment_status":"open","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[4,32],"tags":[59],"class_list":["post-7357","post","type-post","status-publish","format-standard","hentry","category-conference-reports","category-paediatric-care","tag-croi-2005"],"_links":{"self":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/7357","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/users\/4"}],"replies":[{"embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/comments?post=7357"}],"version-history":[{"count":0,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/7357\/revisions"}],"wp:attachment":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/media?parent=7357"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/categories?post=7357"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/tags?post=7357"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}