{"id":10488,"date":"2010-06-01T15:32:35","date_gmt":"2010-06-01T15:32:35","guid":{"rendered":"http:\/\/i-base.info\/htb\/?p=10488"},"modified":"2010-06-01T15:32:35","modified_gmt":"2010-06-01T15:32:35","slug":"pk-of-efavirenz-in-children-dosed-according-to-who-weight-bands","status":"publish","type":"post","link":"https:\/\/i-base.info\/htb\/10488","title":{"rendered":"PK of efavirenz in children dosed according to WHO weight bands"},"content":{"rendered":"

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

Efavirenz (EFV) is used widely in children over 3 years old throughout the world.\u00a0 To date there is limited information about the steady state pharmacokinetics (PK) of EFV in African children.<\/p>\n

A poster from Sabrina Bakeera-Kitaka and colleagues from the ARROW trial showed results from an investigation conducted to determine whether WHO recommended weight band dosing results in optimal EFV exposure in Ugandan children aged 3-12 years.<\/p>\n

In this substudy, 41 HIV-positive children receiving generic EFV plus lamivudine (3TC) and abacavir (ABC) were enrolled in a crossover, PK study of twice vs once daily 3TC+ABC. This was conducted 36 weeks after the children started HAART in ARROW.<\/p>\n

Children were dosed in accordance with WHO weight bands: 200\/250\/300*\/350*mg for those weighing 10\u009615, 15\u009620, 20\u009625, and 25\u009630\u00a0kg respectively, using EFV capsules or *halved 600\u00a0mg tablets. Intensive sampling was performed at t=0, 1, 2, 4, 6, 8, and 12 hours post observed dose on twice-daily HAART at steady state and repeated 4 weeks later including a further 24 hour sample.<\/p>\n

The investigators estimated EFV AUC0-24 and clearance (CL\/kg) using WinNonlin, and predictors of log10AUC and CL were accessed using multivariate mixed models.<\/p>\n

Of the children enrolled, 39 and 37 children had evaluable EFV profiles at the first and second PK sampling respectively.<\/p>\n

The children were 41% (16\/39) boys, 18 (46%) were aged 3\u00966 years and 21 (54%) 7\u009612 years. There were 5, 16, 15, and 3 children in the 10\u009615, 15\u009620, 20\u009625 and 25\u009630\u00a0kg weight-bands, respectively.<\/p>\n

The investigators reported geometric mean (%CV) AUC0-24 of 50.4 (91.7%) and 54.0 (80.8%) h.mg\/L at the first and second sampling respectively. They found no significant variation across weight-bands (p=0.51).<\/p>\n

They noted a large inter- and intra-patient variability in EFV PK parameters (eg 81% and 28% for AUC0-24). They found 15% (6\/39) children at the first sampling, and 7\/37 at the second (7 children in total) had subtherapeutic C8hr and C12hr levels (<1.0mg\/L); 38% (14\/37) had therapeutic C24hr levels at the second sampling. They also found 23% (9\/39) and 27% (10\/37) children in the first and second sampling respectably (11 children in total) with a toxic C8hr and\/or C12hr level (>4.0mg\/L).<\/p>\n

The investigators identified three groups of children using normal mixture modeling:\u00a0 40% with geometric mean AUC0-24 27.2 h.mg\/L, 32% with 49.9 h.mg\/L and 28% with 137 h.mg\/L. They suggested that genetic polymorphisms might play a role.<\/p>\n

Mean clearance overall was 6.8 (SD 3.9) and 6.2 (3.7) L\/h at the first and second sampling respectively (p <\/em>=0.04). C\/F increased by 0.50L\/h for every year older (p=0.05), but was independent of weight (p=0.85), weight-for-age (p=0.52) or height-for-age (p=0.80).<\/p>\n

Overall they found lower exposure than that previously reported in the tablets.<\/p>\n

The ARROW group, are conducting ongoing investigations into the relationship between efavirenz concentrations and toxicity. The children\u0092s viral loads will also be tested retrospectively. They wrote: \u0093Increasing the EFV dose for children should be investigated, and has been proposed by WHO. However higher proportions of children with toxic levels might be expected.\u0094<\/p>\n

Ref: Natukunda E et al. Pharmacokinetics of efavirenz dosed according to the WHO weight-bands in children in Uganda. 17th CROI, 16-19 February 2010, San Francisco. Poster abstract 878.<\/p>\n

http:\/\/www.retroconference.org\/2010\/Abstracts\/37642.htm<\/a><\/p>\n","protected":false},"excerpt":{"rendered":"

Polly Clayden, HIV i-Base Efavirenz (EFV) is used widely in children over 3 years old throughout the world.\u00a0 To date there is limited information about the steady state pharmacokinetics (PK) of EFV in African children. A poster from Sabrina Bakeera-Kitaka …<\/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":[64],"class_list":["post-10488","post","type-post","status-publish","format-standard","hentry","category-conference-reports","category-paediatric-care","tag-croi-2010"],"_links":{"self":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/10488","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=10488"}],"version-history":[{"count":0,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/10488\/revisions"}],"wp:attachment":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/media?parent=10488"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/categories?post=10488"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/tags?post=10488"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}