Introduction: In a pivotal study, apomorphine sublingual film (APL; KYNMOBI Ò ) was an effective and generally well-tolerated ondemand treatment of ''OFF'' episodes in patients with Parkinson's disease (PD), approved across the dose range of 10-30 mg. Pharmacokinetics and comparative bioavailability of APL and two subcutaneous (SC) apomorphine formulations (SC-APO [APOKYN Ò ] and SC-APO-GO [APO-go Ò PEN]) were evaluated in a randomized, threeway crossover, open-label study (NCT03292016). Methods: Patients with PD and ''OFF'' episodes received an open-label randomized sequence of single doses of SC-APO and SC-APO-GO at the currently prescribed dose (2/3/4/5 mg) and APL doses with similar plasma exposure (15/20/25/ 30 mg) with C 1-day washout between formulations. Plasma pharmacokinetics of apomorphine and apomorphine sulfate (major inactive metabolite) were measured 0-6 h postdose. Results: Median time to maximum plasma concentration (t max ) of apomorphine was 0.63-0.75 h for APL and 0.25-0.38 h for SC-APO and SC-APO-GO. Geometric mean maximum plasma concentration (C max ) of apomorphine was 4.31-11.2 ng/ml across APL doses and was generally lower compared with SC apomorphine formulations within dose groups. Area under the concentration-time curve from time 0 to infinity (AUC ? ) was similar across apomorphine formulations within most dose groups. Relative bioavailability of APL was * 17% of SC apomorphine by AUC ? ; SC-APO and SC-APO-GO had similar bioavailability (98% and 83% by AUC ? and C max , respectively). Apomorphine sulfate exposure was * three-fold higher for

Background: To evaluate potential drug-drug interactions with the atypical antipsychotic lurasidone. Methods: Seven phase I studies were conducted to investigate the effects of repeated dosing of ketoconazole, diltiazem, rifampin, or lithium on the pharmacokinetics (PK) of single oral doses of lurasidone, or the effects of repeated dosing of lurasidone on the PK of digoxin, midazolam, or the oral contraceptive norgestimate/ethinyl estradiol. Two 6-week, phase III studies included evaluation of the potential for interaction between lurasidone and lithium or valproate. Maximum serum or plasma concentration (C max ) and area under the concentration-time curve (AUC) were calculated. Results: Concomitant ketoconazole administration resulted in a 6.8-fold increase in lurasidone C max and a 9.3-fold increase in lurasidone AUC; concomitant diltiazem administration resulted in 2.1-and 2.2-fold increases, respectively. Rifampin decreased lurasidone C max and AUC (one-seventh and onefifth of lurasidone alone, respectively). Steady-state dosing with lurasidone increased C max and AUC 0-24 (AUC from time 0 to 24 h postdose) of digoxin by 9% and 13%, respectively, and of midazolam by 21% and 44%, respectively. There were no significant interactions between lurasidone and lithium, valproate, ethinyl estradiol, or norelgestromin (the major active metabolite of norgestimate). Conclusions: Lurasidone PK is altered by strong cytochrome P450 (CYP) 3A4 inhibitors or inducers, and coadministration is contraindicated; whereas moderate CYP3A4 inhibitors have less effect, and lurasidone dosage restrictions are recommended. No dose adjustment

Lurasidone should be administered with food-at least 350 kcal-to ensure maximum exposure.