Background: Consistent with its effect on gastric emptying, exenatide, an injectable treatment for type 2 diabetes,\r\nmay slow the absorption rate of concomitantly administered oral drugs resulting in a decrease in maximum\r\nconcentration (Cmax). This study evaluated the drug interaction potential of exenatide when administered\r\nadjunctively with oral contraceptives, given their potential concomitant use.\r\nMethods: This trial evaluated the effect of exenatide co-administration on single- and multiple-dose\r\npharmacokinetics of a combination oral contraceptive (ethinyl estradiol [EE] 30 �µg, levonorgestrel [LV] 150 �µg\r\n[Microgynon 30�®]). Thirty-two healthy female subjects participated in an open-label, randomised, crossover trial\r\nwith 3 treatment periods (oral contraceptive alone, 1 hour before exenatide, 30 minutes after exenatide). Subjects\r\nreceived a single dose of oral contraceptive on Day 8 of each period and QD doses on Days 10 through 28.\r\nDuring treatment periods of concomitant usage, exenatide was administered subcutaneously prior to morning and\r\nevening meals at 5 �µg BID from Days 1 through 4 and at 10 �µg BID from Days 5 through 22. Single- (Day 8) and\r\nmultiple-dose (Day 22) pharmacokinetic profiles were assessed for each treatment period.\r\nResults: Exenatide did not alter the bioavailability nor decrease daily trough concentrations for either oral\r\ncontraceptive component. No substantive changes in oral contraceptive pharmacokinetics occurred when oral\r\ncontraceptive was administered 1 hour before exenatide. Single-dose oral contraceptive administration 30 minutes\r\nafter exenatide resulted in mean (90% CI) Cmax reductions of 46% (42-51%) and 41% (35-47%) for EE and LV,\r\nrespectively. Repeated daily oral contraceptive administration 30 minutes after exenatide resulted in Cmax\r\nreductions of 45% (40-50%) and 27% (21-33%) for EE and LV, respectively. Peak oral contraceptive concentrations\r\nwere delayed approximately 3 to 4 hours. Mild-to-moderate nausea and vomiting were the most common adverse\r\nevents observed during the trial.\r\nConclusions: The observed reduction in Cmax is likely of limited importance given the unaltered oral contraceptive\r\nbioavailability and trough concentrations; however, for oral medications that are dependent on threshold\r\nconcentrations for efficacy, such as contraceptives and antibiotics, patients should be advised to take those drugs\r\nat least 1 hour before exenatide injection.
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