{"id":12192,"date":"2003-11-01T15:13:54","date_gmt":"2003-11-01T15:13:54","guid":{"rendered":"http:\/\/i-base.info\/htb\/?p=12192"},"modified":"2014-05-27T10:48:49","modified_gmt":"2014-05-27T10:48:49","slug":"boosted-saquinavir-pk-in-once-daily-regimes","status":"publish","type":"post","link":"https:\/\/i-base.info\/htb\/12192","title":{"rendered":"Boosted saquinavir PK in once-daily regimes"},"content":{"rendered":"

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

Marta Boffito and colleagues from Liverpool University investigated steady-state PK of two once-daily boosted saquinavir regimes. Doses studied were 1600mg and 2000mg saquinavir, each boosted by 100mg ritonavir and drug levels were compared to those achieved in the same 18 HIV-positive patients on their original 1000mg\/100mg twice daily regimes.<\/strong><\/p>\n

The interest in these possibilities is heightened by a new 500mg formulation of saquinavir that will considerably reduce the pill count.<\/p>\n

Saquinavir was given with a 40g-fat meal on day one, then switched to 1600\/100mg on day two and switched again on day 12 to 2000\/100mg. Intensive PK was measured by HPMC on days 0, 11 and 22.<\/p>\n

A summary of PK results are shown below in Table 1 but were skewed by one patient who had a Ctrough of over 3000ng\/mL in 2000\/100 mg arm. When this patient was excluded from the analysis the trough levels were reduced by 59% in the 2000\/100mg once-daily arm compared to 1000\/100mg twice-daily. Saquinavir AUC, Cmax and T1\/2 increased by 30%, 136% and 29% respectively when excluding the outlier.<\/p>\n

Although this is a small data set, trough levels at the 1600\/100mg and 2000\/100mg doses are clearly reduced compared to twice-daily dosing. Only one patient in each of the once-daily arms had a saquinavir Ctrough below the minimum effective concentration (MEC) target of 50ng\/mL for treatment na\u00efve patients.<\/p>\n

The authors conclude that the higher drug exposure was driven by higher levels of absorption without evidence of increased toxicity (ALT, AST, glucose, TC and TG) in the short-term. Clearly longer follow-up is required in larger studies before this could be routinely recommended.<\/p>\n

Table 1: PK parameters in eight HIV-positive patients<\/strong><\/p>\n\n\n\n\n\n\n\n\n\n\n\n\n\n
Dose: saquinavir\/ritonavir; Median (IQR)<\/td>\n<\/tr>\n
Parameter<\/td>\n1000\/100 BID<\/td>\n1600\/100 QD<\/td>\n2000\/100 QD<\/td>\n<\/tr>\n
Ctrough (ng\/mL)<\/td>\n569<\/td>\n95<\/td>\n209<\/td>\n<\/tr>\n
Range<\/td>\n138-2226<\/td>\n20-635<\/td>\n31-3128<\/td>\n<\/tr>\n
<\/td>\n(250, 1178)<\/td>\n(57, 192)<\/td>\n(100, 529)<\/td>\n<\/tr>\n
Cmax (ng\/mL)<\/td>\n2152<\/td>\n2835<\/td>\n4241<\/td>\n<\/tr>\n
<\/td>\n(1268, 3321)<\/td>\n(1730, 2631)<\/td>\n(3023, 5902)<\/td>\n<\/tr>\n
AUC0-24hr(ng.h\/mL)<\/td>\n28733<\/td>\n17877<\/td>\n31418<\/td>\n<\/tr>\n
<\/td>\n(14083, 46076)<\/td>\n(1095, 34166)<\/td>\n(22705, 55292)<\/td>\n<\/tr>\n
t1\/2 (hr)<\/td>\n3.31<\/td>\n4.62<\/td>\n4.47<\/td>\n<\/tr>\n
<\/td>\n(2.96, 4.90)<\/td>\n(4.09, 4.93)<\/td>\n(4.21, 5.43)<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

Reference:<\/p>\n

Boffito M, Dickinson L, Hill A et al. Saquinavir\/ritonavir (SQV\/r) pharmacokinetics (PKs) in HIV+ subjects: 1000\/100mg BD vs 1600\/100 and 2000\/100mg once daily (OD). 43rd ICAAC, September, 2003; Abstract A-1612.<\/p>\n","protected":false},"excerpt":{"rendered":"

Simon Collins, HIV i-Base Marta Boffito and colleagues from Liverpool University investigated steady-state PK of two once-daily boosted saquinavir regimes. Doses studied were 1600mg and 2000mg saquinavir, each boosted by 100mg ritonavir and drug levels were compared to those achieved …<\/p>\n","protected":false},"author":4,"featured_media":0,"comment_status":"open","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[34],"tags":[],"class_list":["post-12192","post","type-post","status-publish","format-standard","hentry","category-pk-and-drug-interactions"],"_links":{"self":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/12192","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=12192"}],"version-history":[{"count":0,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/12192\/revisions"}],"wp:attachment":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/media?parent=12192"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/categories?post=12192"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/tags?post=12192"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}