{"id":7865,"date":"2010-02-21T10:02:55","date_gmt":"2010-02-21T10:02:55","guid":{"rendered":"http:\/\/moomango.co.uk\/htb\/?p=7865"},"modified":"2013-08-06T06:41:47","modified_gmt":"2013-08-06T06:41:47","slug":"no-clinically-relevant-interactions-between-tmc278-and-oral-contraceptives-norethindrone-plus-ethinylestradiol","status":"publish","type":"post","link":"https:\/\/i-base.info\/htb\/7865","title":{"rendered":"No clinically relevant interactions between TMC278 and oral contraceptives (norethindrone plus ethinylestradiol)"},"content":{"rendered":"

Polly Clayden, HIV\u00a0i-Base<\/strong><\/p>\n

An open label trial conducted by Crauwels and colleagues evaluated the pharmacokinetic (PK) interaction between TMC278 and norethindrone plus<\/strong>\u00a0ethinylestradiol.<\/strong><\/p>\n

In this analysis, 18 HIV-negative volunteers received 1mg norethindrone plus ethinylestradiol 35ug (combined oral contraceptive pill, Ovysmen) once a day\u00a0for three sequential 21-day cycles spaced with with 7-day intervals. TMC278 was co-administered for the first 15 days of the third cycle at a once daily\u00a0dose of 25 mg. TMC278 and Ovysmen were taken within 10 minutes after breakfast.<\/p>\n

At day 15 of the second and third cycles 24 PK profiles of norethindrone, ethinylestradiol and TMC278 were obtained. Plasma samples were analysed using\u00a0validated LC-MS\/MS methods, with a lower limit of quantification of 1.0 ng\/mL for TMC278, 50.0 pg\/mL for norethindrone and 2.0 pg\/mL for ethinylestradiol.\u00a0Serum levels of progesterone luteinising hormone (LH) and follicle-stimulating hormone (FSH) were determined on days 1 and 14 of the second and third\u00a0cycles.<\/p>\n

PK parameters were calculated using non-compartmental analysis. Statistical analysis compared the test treatment, Ovysmen+TMC278 to the reference, Ovysmen\u00a0alone.<\/p>\n

The women in the study were a median age of 26 years, weight 69.5kg and BMI 24.6. The majority (67%) were white.<\/p>\n

The investigators reported no effect on norethindrone PK when co-administered with TMC278. With ethinylestriol, neither the Cmin, nor the AUC24h were\u00a0affected and Cmax increased by 17% in the presence of TMC278. This increase is not expected to have a clinically relevant effect. See Table 1 for results\u00a0of PK parameter ratios for norethindrone and ethinylestriol in the presence of TMC278.<\/p>\n

Table 1: PK parameter ratios for norethindrone and ethinylestriol in the presence of TMC278<\/strong><\/p>\n\n\n\n\n\n\n
Parameter<\/strong><\/td>\nn\/n<\/strong><\/td>\nNorethindrone (90% CI)<\/strong><\/td>\nEthinylestradiol (90%
\nCI)<\/strong><\/td>\n<\/tr>\n
AUC24h pg.h\/mL<\/td>\n14\/15<\/td>\n0.89 (0.84-0.94)<\/td>\n1.14 (1.10-1.19)<\/td>\n<\/tr>\n
Cmax pg.h\/m<\/td>\n15\/17<\/td>\n0.94 (0.83-1.06)<\/td>\n1.17 (1.06-1.30)<\/td>\n<\/tr>\n
Cmin pg.h\/mL<\/td>\n15\/17<\/td>\n0.99 (0.90-1.08)<\/td>\n1.09
\n(1.03-1.16)<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

Steady state PK parameters of TMC278 25mg\/QD in the presence of noretindrone and ethinylestriol were comparable\u00a0to values observed in previous trials of TMC278 alone. TMC278 25mg\/QD had no clinically relevant effect on FSH, LH or progesterone serum levels in the\u00a0presence of noretindrone and ethinylestriol.<\/p>\n

The investigators concluded that the contraceptive efficacy of 1mg norethindrone plus ethinylestradiol 35ug is expected to be maintained in the presence\u00a0of TMC278 25mg\/qd without dose modifications.<\/p>\n

Ref: Crauwels et al. Pharmacokinetic interaction study between TMC278 an NNRTI, and the contraceptives northindrone plus ethinylesradiol. Abstract\u00a0PE4.3\/3<\/p>\n","protected":false},"excerpt":{"rendered":"

Polly Clayden, HIV\u00a0i-Base An open label trial conducted by Crauwels and colleagues evaluated the pharmacokinetic (PK) interaction between TMC278 and norethindrone plus\u00a0ethinylestradiol. In this analysis, 18 HIV-negative volunteers received 1mg norethindrone plus ethinylestradiol 35ug (combined oral contraceptive pill, Ovysmen) once …<\/p>\n","protected":false},"author":4,"featured_media":0,"comment_status":"open","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[4,44,34],"tags":[72],"class_list":["post-7865","post","type-post","status-publish","format-standard","hentry","category-conference-reports","category-womens-health","category-pk-and-drug-interactions","tag-eacs-12th-2009"],"_links":{"self":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/7865","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=7865"}],"version-history":[{"count":0,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/7865\/revisions"}],"wp:attachment":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/media?parent=7865"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/categories?post=7865"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/tags?post=7865"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}