{"id":15793,"date":"2011-10-01T12:08:04","date_gmt":"2011-10-01T12:08:04","guid":{"rendered":"http:\/\/i-base.info\/htb\/?p=15793"},"modified":"2011-10-01T12:08:04","modified_gmt":"2011-10-01T12:08:04","slug":"atazanavir-pharmacokinetics-in-infants-children-and-adolescents","status":"publish","type":"post","link":"https:\/\/i-base.info\/htb\/15793","title":{"rendered":"Atazanavir pharmacokinetics in infants, children and adolescents"},"content":{"rendered":"

Polly Clayden HIV i-Base<\/strong><\/p>\n

An article in the July 31 2011 edition of AIDS describes atazanavir (ATV) pharmacokinetics (PKP in infants, children and adolescents given alone and boosted with ritonavir (ATV\/r). Jennifer J Kiser and colleagues from the IMPAACT 1020A phase I\/II study evaluated two formulations of ATV, capsules and a dispersible orange-vanilla flavoured powder across a range of age groups in treatment naive and experienced participants from the United States and South Africa.<\/p>\n

Participants were aged 91 days to 21 years and received unboosted or boosted (using ritonavir capsule or liquid formulations) ATV as part of a combination antiretroviral regimen. All participants underwent intensive 24-hour PK sampling on day 7; 195 enrolled and 172 had evaluable data.<\/p>\n

All groups were started at a target dose of 310mg\/m2. To establish an acceptable ATV or ATV\/r dose for an age group, 10 participants had to meet PK and safety criteria as defined by the protocol.<\/p>\n

For PK these were: ATV AUC AUC0-24hr of at least 30,000ng x h\/mL and C24 of at least 60ng\/mL in at least 80% of participants; no AUC0-24hr less than 15,000ng x h\/mL and median AUC0-24hr of 60,000ng x h\/m\/L or less. And for safety: no life threatening toxicities; one or fewer participants with grade 3 or 4 toxicities (excluding bilirubin) linked to study treatment, and two or fewer participants with total bilirubin values greater than 5.1 times the upper limit of normal.<\/p>\n

If these criteria were not met, the ATV starting dose was modified for the age group, either increased to 415, 520 then 620mg\/m2 or decreased to 205mg\/m2.<\/p>\n

Nearly half (45%) of the participants were antiretroviral naive at enrollment; 62% received ATV capsules and the remaining 38% ATV powder.<\/p>\n

The investigators found unboosted ATV capsules met PK criteria at a dose of 520mg\/m2 for participants >2 to 13 years of age and 620mg\/m2 for those >13 to 21 years of age. Boosted ATV capsules met PK criteria at a dose of 205mg\/m2 for those >2 to 21 years of age. Boosted ATV powder met PK criteria at a dose of 310mg\/m2 for those >2 to 13 years of age.<\/p>\n

Infants and young children aged 3 months to 2 years dosed with boosted ATV powder failed to meet PK criteria. There was a lot of intersubject variability in exposures this age group so that a dose escalation to 415mg\/mL may have given ATV exposures in some young children greater than 90,000ng x h\/mL.<\/p>\n

The investigators wrote that additional studies are needed in this age group to determine if an appropriate ritonavir boosted dose can be identified.<\/p>\n

Reference:<\/p>\n

Kiser JJ et al. Atazanavir and atazanavir\/ritonavir pharmacokinetics in HIV infected infants, children and adolescents. AIDS 2011, 25:1489-96.<\/p>\n","protected":false},"excerpt":{"rendered":"

Polly Clayden HIV i-Base An article in the July 31 2011 edition of AIDS describes atazanavir (ATV) pharmacokinetics (PKP in infants, children and adolescents given alone and boosted with ritonavir (ATV\/r). Jennifer J Kiser and colleagues from the IMPAACT 1020A …<\/p>\n","protected":false},"author":2,"featured_media":0,"comment_status":"open","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[32],"tags":[],"class_list":["post-15793","post","type-post","status-publish","format-standard","hentry","category-paediatric-care"],"_links":{"self":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/15793","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\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/comments?post=15793"}],"version-history":[{"count":0,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/15793\/revisions"}],"wp:attachment":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/media?parent=15793"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/categories?post=15793"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/tags?post=15793"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}