{"id":4440,"date":"2009-08-23T10:17:29","date_gmt":"2009-08-23T09:17:29","guid":{"rendered":"http:\/\/moomango.co.uk\/htb\/?p=4440"},"modified":"2013-08-16T13:14:39","modified_gmt":"2013-08-16T13:14:39","slug":"raltegravir-pk-in-blood-plasma-and-the-genital-tract","status":"publish","type":"post","link":"https:\/\/i-base.info\/htb\/4440","title":{"rendered":"Raltegravir PK in blood plasma and the genital tract"},"content":{"rendered":"

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

Jones and colleagues from University of North Carolina presented results of an open label single-arm pharmacokinetic study in seven HIV-negative women, comparing drug levels in blood plasma (BP) and cervical vaginal fluid (CVF) following standard dose raltegravir (400mg BID).<\/strong> [1]<\/p>\n

Raltegravir was taken with a 545 kcal meal (18% fat, 70% carbs, 12% protein) and nine paired samples were taken on day one and day seven.<\/p>\n

Although median levels achieved in CVF were 63% and ~100% of those in BP at day 1 and seven respectively (see Table 1), the IQR for the CVF:BP ratios showed such a wide interpatient variability crossing 1.0 that this couldn\u0092t be relied on for individual patient results [0.26-1.91 and 0.41-1.69 respectively].<\/p>\n

Notably, elimination was slowed in CVF with a two-fold increase in half life (7 [5-12] vs. 17 [14-23] hours) compared to BP. Steady-state was reached after 2 days in BP and 4 days in CVF.<\/p>\n

Table 1: Median [IQR] raltegravir levels in BP and CVF<\/strong><\/p>\n\n\n\n\n\n\n\n\n\n\n\n\n\n
<\/td>\nBP<\/td>\nCVF<\/td>\n<\/tr>\n
Day 1<\/td>\n<\/tr>\n
Cmax (ng\/mL)<\/td>\n790 [249-2585]<\/td>\n631 [327-1658]<\/td>\n<\/tr>\n
C12h (ng\/mL)<\/td>\n55 [10-255]<\/td>\n607 [321-1283]<\/td>\n<\/tr>\n
AUC 0-12h (ng*hr\/mL)<\/td>\n3393 [717-7322]<\/td>\n1677 [910-66,716]<\/td>\n<\/tr>\n
Tmax (hr)<\/td>\n6 [3-6]<\/td>\n12 [8-12]<\/td>\n<\/tr>\n
Day 7<\/td>\n<\/tr>\n
Cmax (ng\/mL)<\/td>\n1874 [403-2200]<\/td>\n1272 [879-2388]<\/td>\n<\/tr>\n
C12h (ng\/mL)<\/td>\n19 [10-31]<\/td>\n282 [142-523]<\/td>\n<\/tr>\n
AUC 0-12h (ng*hr\/mL)<\/td>\n11,911 [6979-15,998]<\/td>\n9769 [2238-19,659]<\/td>\n<\/tr>\n
Tmax (hr)<\/td>\n8 [6-12]<\/td>\n3 [0.5-3.0]<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

Comment<\/h3>\n

Bearing in mind these data are only showing IQR in a very small sample of women, the pharmacokinetics of raltegravir at steady state, show at least a 10-fold interpatient range in most parameters, in both BP and CVF.<\/strong><\/p>\n

Reference:<\/p>\n

Jones A et al. First-dose and steady-state pharmacokinetics (PK) of raltegravir in the genital tract of HIV uninfected women. 10th International Workshop on Clinical Pharmacology of HIV Therapy, 15-17 April 2009, Amsterdam. Oral abstract O-06.<\/p>\n","protected":false},"excerpt":{"rendered":"

Simon Collins, HIV i-Base Jones and colleagues from University of North Carolina presented results of an open label single-arm pharmacokinetic study in seven HIV-negative women, comparing drug levels in blood plasma (BP) and cervical vaginal fluid (CVF) following standard dose …<\/p>\n","protected":false},"author":4,"featured_media":0,"comment_status":"open","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[4],"tags":[133],"class_list":["post-4440","post","type-post","status-publish","format-standard","hentry","category-conference-reports","tag-pk-workshop-10th-2009"],"_links":{"self":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/4440","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=4440"}],"version-history":[{"count":0,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/4440\/revisions"}],"wp:attachment":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/media?parent=4440"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/categories?post=4440"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/tags?post=4440"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}