{"id":7860,"date":"2010-02-21T02:23:15","date_gmt":"2010-02-21T02:23:15","guid":{"rendered":"http:\/\/moomango.co.uk\/htb\/?p=7860"},"modified":"2013-08-06T06:55:19","modified_gmt":"2013-08-06T06:55:19","slug":"other-selected-pk-and-drug-interaction-summaries-from-eacs","status":"publish","type":"post","link":"https:\/\/i-base.info\/htb\/7860","title":{"rendered":"Other selected PK and drug interaction summaries from EACS"},"content":{"rendered":"

www.hiv-druginteractions.org <\/strong><\/p>\n

This report summarises drug interaction and pharmacology studies presented at this recent meeting. Unless stated otherwise, all references are to the 12th<\/strong>\u00a0European AIDS Conference (EACS), 11-14 November 2009, Cologne.<\/strong><\/p>\n

Raltegravir\u00a0and\u00a0famotidine\u00a0or\u00a0omeprazole<\/h2>\n

The effect of famotidine (20 mg single\u00a0dose 2 h before raltegravir) or omeprazole (20 mg once-daily for 5 days, 2 h before raltegravir) was studied in 18 HIV-positive subjects stable on\u00a0raltegravir (400 mg twice-daily) regimens.\u00a0\u00a0 Coadministration of famotidine increased raltegravir AUC, Cmax and Ctrough by 45%, 60% and 6% respectively.\u00a0Omeprazole increased raltegravir AUC, Cmax and Ctrough by 39%, 51% and 24%, respectively.\u00a0 The increases were not clinically significant and raltegravir\u00a0may be coadministered with famotidine or omeprazole without dose adjustment.<\/p>\n

COMMENT<\/strong><\/h3>\n

This\u00a0effect\u00a0is\u00a0less\u00a0than\u00a0previously\u00a0seen\u00a0in\u00a0healthy\u00a0volunteers. <\/strong><\/p>\n

Ref: Rhame F et al. Effects of famotidine and omeprazole on raltegravir pharmacokinetics in HIV-infected persons.\u00a0 12th EACS, 11-14 November 2009,
\nCologne. Abstract PE4.1\/1.<\/p>\n

P450\u00a0and\u00a0P-gp\u00a0activities\u00a0in\u00a0HIV-positive\u00a0and\u00a0HIV-negative\u00a0subjects<\/h2>\n

The activity of CYP3A, 2D6 and P-gp were\u00a0investigated in 30 HIV positive, treatment naive patients and 12 HIV-negative controls. Subjects were given a \u0093phenotyping cocktail\u0094 containing midazolam\u00a0(1.5mg, intestinal and hepatic CYP3A), dextromethorphan (30 mg, CYP2D6), digoxin (0.5 mg, P-gp) and IV midazolam (1.0mg, hepatic CYP3A).<\/p>\n

The activities of CYP3A, CYP2D6 and P-gp were lower in the HIV-positive subjects, but with the exception of CYP3A, the differences were small. Total CYP3A\u00a0activity was 0.493-fold lower in HIV-positive subjects than in HIV-negative controls.<\/p>\n

Within group variability was greater than between group variability, making it unlikely that dose adaptations based on infection status would be useful.<\/p>\n

Ref: Jetter A et al. Are there differences between healthy volunteers and HIV-infected patients in the activities of CYP3A, CYP2D6 and P-glycoprotein.\u00a012th EACS, 11-14 November 2009, Cologne.\u00a0 Abstract PE4.1\/9.<\/p>\n

MVC\u00a0and\u00a0CYP450\u00a0inhibitors\u00a0or\u00a0inducers<\/h2>\n

Maraviroc trough concentrations were determined\u00a0in HIV positive subjects receiving maraviroc in combination with CYP450 inhibitors or inducers.<\/p>\n

Median maraviroc trough concentrations were 83 ng\/mL, with 24% being below target (50 ng\/mL) in subjects receiving maraviroc 150 mg twice daily with a\u00a0boosted PI (not TPV or APV).\u00a0 In subjects receiving maraviroc 300 mg twice daily with a boosted PI, the median trough concentration was 264 ng\/ml and 9%\u00a0were below target.<\/p>\n

When maraviroc was administered as 300 mg twice daily without a boosted PI or NNRTI, median trough concentrations were 47 ng\/mL and 55% were below target.\u00a0Coadministration of maraviroc 600 mg twice daily with etravirine resulted in median trough concentrations of 77 ng\/mL, of which 19% were below target.<\/p>\n

COMMENT<\/strong><\/h3>\n

There is data suggesting that the average concentrations (Cavg) may be a better parameter to correlate with viral response. <\/strong><\/p>\n

<\/strong> Ref:\u00a0Sari-Chaaf Zet al. Maraviroc boosted (or not) by ritonavir? Pharmacokinetic results from routine therapeutic drug monitoring. 12th EACS, 11-14 November\u00a02009, Cologne. Abstract PE4.2\/1.<\/p>\n

Abacavir\u00a0and\u00a0darunavir\/r\u00a0or\u00a0raltegravir<\/h2>\n

This study investigated the steady-state plasma pharmacokinetics of\u00a0abacavir (600 mg once daily) when co-administered with darunavir\/ritonavir (900\/100 mg once daily) or raltegravir (400 mg twice daily) to 19 HIV positive\u00a0subjects.<\/p>\n

Abacavir AUC, Cmax and Cmin decreased by 27%, 22% and 38%, respectively in the presence of darunavir\/ritonavir.\u00a0 When coadministered with raltegravir, the\u00a0AUC and Cmax of abacavir increased by 3% and 6%, respectively; Cmin decreased by 17%. It is important to relate the change in plasma abacavir exposure to\u00a0the active intracellular carbovir triphosphate and a study is in progress.<\/p>\n

Ref: Jackson\u00a0A et\u00a0al.\u00a0Pharmacokinetics (PK) of\u00a0plasma abacavir (ABC) in the\u00a0absence and in\u00a0the\u00a0presence of\u00a0darunavir\/ritonavir\u00a0(DRV\/r)\u00a0or\u00a0raltegravir\u00a0(RAL)\u00a0in\u00a0HIV-infected\u00a0subjects.\u00a012th EACS, 11-14 November 2009, Cologne. Abstract\u00a0PE4.3\/2.<\/p>\n

TMC278\u00a0and\u00a0oral\u00a0contraceptives<\/h2>\n

The pharmacokinetic\u00a0interaction between TMC278 (25mg once daily) and an oral contraceptive containing norethindrone\/ethinylestradiol (1\/0.035mg) was studied in 18\u00a0HIV negative females.\u00a0 Norethindrone pharmacokinetics were unaffected by TMC278 (11% decrease in AUC, 6% decrease in Cmax, 1% decrease in Cmin).<\/p>\n

There was no statistically significant change in ethinylestradiol AUC (14% increase) or Cmin (9% increase), but Cmax increased by 17%, however, this is\u00a0not expected to be clinically significant.\u00a0 Pharmacokinetics of TMC278 were within the expected range.\u00a0 There was no marked effect on FSH, LH and\u00a0progesterone serum levels.<\/p>\n

TMC278 and oral contraceptives containing norethindrone\/ethinylestradiol can be coadministered without dose modifications.<\/p>\n

Ref: Crauwels H et al. Pharmacokinetic interaction study between TMC278, a next-generation nonnucleoside reverse\u00a0 transcriptase inhibitor (NNRTI), and the\u00a0contraceptives norethindrone plus ethinylestradiol. 12th EACS, 11-14 November 2009, Cologne. Abstract PE4.3\/3.<\/p>\n

Darunavir and raltegravir\u00a0interaction<\/h2>\n

Darunavir trough concentrations were determined in 117 samples from 55 HIV-positive patients receiving darunavir containing regimens with\u00a0either a NRTI or raltegravir.<\/p>\n

Mean (\u00b1 sd) darunavir concentrations were higher in the NRTI subjects than in the raltegravir subjects (4.20 \u00b1 2.35 vs 2.63 \u00b1 84 mg\/L).\u00a0 However, the\u00a0proportion of subjects with undetectable viral loads (<50 copies\/mL) was higher in the raltegravir group than in the NRTI group.<\/p>\n

After adjusting for time from last drug intake and concomitant drugs, a multivariate linear regression model confirmed raltegravir to be independently\u00a0related to lower darunavir concentrations.<\/p>\n

The mechanism of this unexpected interaction remains to be determined, but it does not appear to be virologically significant.<\/p>\n

COMMENT <\/strong><\/h3>\n

This data is consistent with a previous report from Garvey et al presentated at the IAS meeting in Cape Town\u00a0 (IAS 2009, LBPEB08).\u00a0 The absolute\u00a0darunavir concentrations in the Fabbiani study are higher than previously reported.<\/strong><\/p>\n

Ref: Fabbiani M et al. Unexpected drug interaction between darunavir and raltegravir. 12th EACS, 11-14 November 2009, Cologne. Abstract PE4.3\/4.<\/p>\n

Raltegravir\u00a0and\u00a0unboosted\u00a0atazanavir<\/h2>\n

The steady state pharmacokinetics of raltegravir (400 mg twice daily) and unboosted atazanavir (300 mg twice\u00a0daily) were determined in 22 HIV-positive subjects who switched from their current regimen.<\/p>\n

Atazanavir geometric mean AUC, Cmax and Ctrough were 14454 ng.h\/ml, 2275 ng\/ml and 419 ng\/mL respectively. Raltegravir geometric mean AUC, Cmax and\u00a0Ctrough were 7112 ng.h\/ml, 1680 ng\/mL and 62 ng\/mL.\u00a0 Three subjects (14%) had atazanavir trough concentrations below 100 ng\/mL.<\/p>\n

At the time of switch, 79% subjects had undetectable viral load, but at week 24, all subjects had undetectable viral loads.<\/p>\n

COMMENT <\/strong><\/p>\n

These data are generally consistent with Zhu et al (CROI 2009, abstract 696).<\/strong><\/p>\n

Ref: Ripamonti D et al. Steady-state pharmacokinetics, efficacy, safety and tolerability of dual regimen with atazanavir\u00a0 (300mg\u00a0 bid)\u00a0 plus\u00a0 raltegravir \u00a0(400mg\u00a0 bid)\u00a0 in\u00a0 HIV-1-infected\u00a0 patients:\u00a0 24-week\u00a0 results\u00a0 (CARDS\u00a0 study). 12th EACS, 11-14 November 2009, Cologne. Abstract LBPE4.3\/5.<\/p>\n

Nevirapine\u00a0and efavirenz concentrations, during\u00a0and\u00a0after\u00a0stopping\u00a0rifampicin<\/h2>\n

Concentrations (12 h post dose) of nevirapine (400 mg\/day, n=71) and efavirenz\u00a0(600 mg\/day, n=71) were determined at 6 and 12 weeks after starting rifampicin and then after rifampicin had been discontinued.\u00a0 Mean \u00b1SD concentrations\u00a0for nevirapine at weeks 6, 12 and after discontinuation were 5.6 \u00b1 3.6, 5.5 \u00b1 2.6 and 6.7 \u00b1 3.5 mg\/L, respectively.<\/p>\n

Efavirenz concentrations at the same time points were 4.5 \u00b1 4.3, 3.8 \u00b1 3.5 and 3.5 \u00b1 2.7 mg\/L, respectively.\u00a0 Patients on efavirenz showed greater\u00a0inter-patient variability whilst receiving rifampicin than patients on nevirapine.<\/p>\n

Ref: Manosuthi W et al. Serial monitoring of drug concentrations while on and off rifampicin between standard doses of nevirapine-based and\u00a0efavirenz-based antiretroviral regimens. 12th EACS, 11-14 November 2009, Cologne. Abstract PE4.6\/1.<\/p>\n

Traditional\u00a0medicine\u00a0use\u00a0in\u00a0Uganda<\/h2>\n

The use of\u00a0African herbal medicines in HIV-positive subjects receiving antiretroviral therapy was assessed in four districts of Uganda by interviewing traditional\u00a0medicine practitioners (n=25) and HIV-positive subjects (n=44).<\/p>\n

Over 100 plant species were identified, with approximately 80% of preparations being taken orally.<\/p>\n

Multi-plant preparations were common in 75% districts, with mono-plant preparations being predominant in one district.\u00a0 Plant parts frequently used were\u00a0leaves (33%), stem bark (23%) and root bark (18%). The priority plants identified included Aloe sp, Erythina abyssinica, Sarcocephalus latifolius,\u00a0Psorospermum febrifugum, Mangifera indica, Warburgia salutaris and Albizia coriaria.<\/p>\n

COMMENT<\/strong><\/h3>\n

The widespread use of traditional medicines with largely unknown effects on drug disposition indicates the need for studies in this area.<\/strong><\/p>\n

Ref: Lamorde M et al. Traditional medicine practices in the context of HIV in Uganda. 12th EACS, 11-14 November 2009, Cologne. Abstract\u00a0PE19.9\/1.<\/p>\n","protected":false},"excerpt":{"rendered":"

www.hiv-druginteractions.org This report summarises drug interaction and pharmacology studies presented at this recent meeting. Unless stated otherwise, all references are to the 12th\u00a0European AIDS Conference (EACS), 11-14 November 2009, Cologne. Raltegravir\u00a0and\u00a0famotidine\u00a0or\u00a0omeprazole The effect of famotidine (20 mg single\u00a0dose 2 h …<\/p>\n","protected":false},"author":4,"featured_media":0,"comment_status":"open","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[4,34],"tags":[72],"class_list":["post-7860","post","type-post","status-publish","format-standard","hentry","category-conference-reports","category-pk-and-drug-interactions","tag-eacs-12th-2009"],"_links":{"self":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/7860","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=7860"}],"version-history":[{"count":0,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/7860\/revisions"}],"wp:attachment":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/media?parent=7860"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/categories?post=7860"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/tags?post=7860"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}