{"id":15959,"date":"2011-12-01T13:27:59","date_gmt":"2011-12-01T13:27:59","guid":{"rendered":"http:\/\/i-base.info\/htb\/?p=15959"},"modified":"2011-12-01T13:27:59","modified_gmt":"2011-12-01T13:27:59","slug":"higher-plasma-levels-of-tenofovir-and-darunavir-but-not-efavirenz-in-older-patients","status":"publish","type":"post","link":"https:\/\/i-base.info\/htb\/15959","title":{"rendered":"Higher plasma levels of tenofovir and darunavir but not efavirenz in older patients"},"content":{"rendered":"

Simon Collins, HIV i-Base<\/strong><\/p>\n

Several studies looked at the association between older age and antiretroviral pharmacokinetics (PK).<\/p>\n

Tenofovir<\/h2>\n

Muge Cevik from the Chelsea and Westminster Hospital London reported results from a PK study suggesting that tenofovir clearance is significantly reduced with increasing age and resulting in higher drug levels (AUC and Ctrough). [1]<\/p>\n

This included steady-state plasma levels from 52 men and 2 women (12 of whom were on PI\/r-based combinations). Median age was 54 years (range 40?81 years) with only two people younger than 50. Samples were drawn randomly and population pharmacokinetics applied to predict values.<\/p>\n

Tenofovir median clearance (CL\/F), AUC (24hr) and Ctrough (C24) were 110.0 L\/r (27.4?248.3). 2.2 mg.hr\/L (1.0?9.0), and 0.06 mg\/L (0.01?0.3) respectively.<\/p>\n

Increasing age was significantly associated with slower clearance (p=0.0012), higher AUC (p=0.0012) and higher Ctrough (p=0.0017). People older than 60 had significantly lower clearances (p=0.0447) and higher AUC (p=0.0457) than those younger than 60.<\/p>\n

No PK differences were seen between PI and NNRTI based combinations (p=0.08).<\/p>\n

Efavirenz and darunavir\/ritonavir<\/h2>\n

A similar analysis was presented by Ahmed and colleagues from the same group at Chelsea and Westminster on the PK of efavirenz or darunavir\/ritonavir used by older patients (median age was 54 years (range 27-77) and 56 years (28-76), respectively). [2]<\/p>\n

In 70 men and 7 women taking efavirenz, no differences were seen in any PK parameter when comparisons were made between people older and younger than 50 (all p-values >0.05 for between age comparisons).<\/p>\n

In 33 men and one woman taking darunavir\/ritonavir (23 using once-daily) oral clearance was significantly lower in people over 50 years old (10.3 vs 13.0 L\/h; p=0.027) with higher AUC (80.9 vs 61.6 mg.h\/L; p=0.021) and Ctrough levels (1.9 vs 1.2 mg\/L; p=0.008) than those younger than 50.<\/p>\n

Once-daily vs twice-daily could not be assessed because of unequal age distribution between the two dosing regimens.<\/p>\n

References:<\/p>\n

    \n
  1. Cevik M et al. Tenofovir (TFV) pharmacokinetics (PK) in HIV infected individuals over 40 years of age. 13th EACS, 12?15 October 2011, Belgrade. Abstract PS 6\/1.<\/li>\n
  2. Ahmed A et al. Efavirenz and Darunavir Plasma Concentrations in HIV-infected Patients Aged 50 Years or over. 13th EACS, 12?15 October 2011, Belgrade. Abstract PE6.2\/1.<\/li>\n<\/ol>\n","protected":false},"excerpt":{"rendered":"

    Simon Collins, HIV i-Base Several studies looked at the association between older age and antiretroviral pharmacokinetics (PK). Tenofovir Muge Cevik from the Chelsea and Westminster Hospital London reported results from a PK study suggesting that tenofovir clearance is significantly reduced …<\/p>\n","protected":false},"author":2,"featured_media":0,"comment_status":"open","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[4,34],"tags":[73],"class_list":["post-15959","post","type-post","status-publish","format-standard","hentry","category-conference-reports","category-pk-and-drug-interactions","tag-eacs-13th-2011"],"_links":{"self":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/15959","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=15959"}],"version-history":[{"count":0,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/15959\/revisions"}],"wp:attachment":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/media?parent=15959"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/categories?post=15959"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/tags?post=15959"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}