Effects of Food on the Relative Bioavailability of Lapatinib in Cancer Patients

Purpose This study was conducted to characterize the effect of food on the relative bioavailability of lapatinib. Patients and Methods A single 1,500-mg, oral dose of lapatinib was administered to 27 patients with advanced solid tumors on each of three occasions that were 1 week apart, in random order: after an overnight fast, with a low-fat breakfast, and with a high-fat breakfast. Results The low-fat breakfast produced mean increases in lapatinib area under the concentration-time curve (AUC) of 167% (2.67-fold) and maximum concentration (Cmax) of 142% (2.42-fold). The high-fat breakfast produced mean increases in lapatinib AUC of 325% (4.25-fold) and Cmax of 203% (3.03-fold) compared with the fasted state. Increased bioavailability in the fed state did not significantly decrease relative variability. Therefore, absolute variability in systemic exposure was increased. Conclusion These large increases in lapatinib bioavailability and absolute variability support the recommendation for dosing in the fasted state to achieve consistent therapeutic exposure. Prescribers and patients should consider the potential consequences of toxicity or diminished efficacy that might result from dosing without regard to variations in diet.

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Effect of Food on the Pharmacokinetics of the Integrase Inhibitor Dolutegravir

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.05739-11 ◽

2011 ◽

Vol 56 (3) ◽

pp. 1627-1629 ◽

Cited By ~ 62

Author(s):

Ivy Song ◽

Julie Borland ◽

Shuguang Chen ◽

Parul Patel ◽

Toshihiro Wajima ◽

...

Keyword(s):

Single Dose ◽

Healthy Subjects ◽

Integrase Inhibitor ◽

High Fat ◽

Time Curve ◽

Clinical Safety ◽

Fasted State ◽

Concentration Time ◽

Rate Of Absorption ◽

Effect Of Food

ABSTRACTHealthy subjects received dolutegravir at 50 mg in a single-dose crossover study while they were in the fasted state or with low-, moderate-, or high-fat meals. Food increased dolutegravir exposure and reduced the rate of absorption. The area under the concentration-time curve from 0 h to infinity (AUC0–∞) increased by 33%, 41%, and 66% when administered with low-, moderate-, or high-fat meals, respectively, compared with fasting. This increase in dolutegravir exposure is not anticipated to impact clinical safety, and therefore dolutegravir can be taken with or without food and without regard to fat content.

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The effect of food on the pharmacokinetics of oral ivermectin

Journal of Antimicrobial Chemotherapy ◽

10.1093/jac/dkz466 ◽

2019 ◽

Author(s):

Urs Duthaler ◽

Rory Leisegang ◽

Mats O Karlsson ◽

Stephan Krähenbühl ◽

Felix Hammann

Keyword(s):

Food Effect ◽

Neglected Tropical Diseases ◽

Relative Bioavailability ◽

Field Trials ◽

Population Based ◽

High Fat ◽

Time Profiles ◽

Fasted State ◽

State Administration ◽

Effect Of Food

Abstract Background Ivermectin is an older anthelminthic agent that is being studied more intensely given its potential for mass drug administration against scabies, malaria and other neglected tropical diseases. Its pharmacokinetics (PK) remain poorly characterized. Furthermore, the majority of PK trials are performed under fasted-state dosing conditions, and the effect of food is therefore not well known. To better plan and design field trials with ivermectin, a model that can account for both conditions would be valuable. Objectives To develop a PK model and characterize the food effect with single oral doses of ivermectin. Patients and methods We performed a population-based PK analysis of data pooled from two previous trials of a single dose of 12 mg ivermectin, one with dosing after a high-fat breakfast (n=12) and one with fasted-state dosing (n=3). Results The final model described concentration–time profiles after fed and fasted dosing accurately, and estimated the food effect associated with relative bioavailability to 1.18 (95% CI 1.10–1.67). Conclusions In this analysis, the effect of a high-fat breakfast compared with a fasted-state administration of a single oral dose of 12 mg ivermectin was minimal.

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High-Fat Breakfast Increases Bioavailability of Albendazole Compared to Low-Fat Breakfast: Single-Dose Study in Healthy Subjects

Frontiers in Pharmacology ◽

10.3389/fphar.2021.664465 ◽

2021 ◽

Vol 12 ◽

Author(s):

Dolores Ochoa ◽

Miriam Saiz-Rodríguez ◽

Esperanza González-Rojano ◽

Manuel Román ◽

Sergio Sánchez-Rojas ◽

...

Keyword(s):

Healthy Volunteers ◽

Systemic Exposure ◽

High Fat ◽

Low Fat ◽

Time Curve ◽

Single Dose Study ◽

Albendazole Sulfoxide ◽

Dose Study ◽

Two Stages ◽

Oral Doses

Purpose: Albendazole is a benzimidazole carbamate drug with anthelmintic and antiprotozoal activity against intestinal and tissue parasites. It has been described that the administration with meals increases albendazole absorption. Our aim was to compare the systemic exposure in healthy volunteers of two albendazole formulations after a single oral dose under fed conditions and to evaluate the effect of breakfast composition on albendazole and albendazole sulfoxide bioavailability.Methods: 12 healthy volunteers were included in a 4-period, 4-sequence, crossover, open, randomized, bioequivalence clinical trial, including two stages to compare two formulations of albendazole. Single oral doses of 400 mg albendazole were administered under fed conditions (a low-fat breakfast in first stage and a high-fat breakfast in the second) separated by 7-day washout periods. Plasma albendazole and albendazole sulfoxide concentrations were measured by HPLC-MS/MS.Findings: Albendazole absorption was clearly influenced by the meal composition. A high-fat breakfast increased albendazole and albendazole sulfoxide area under the concentration–time curve (AUC) and maximum concentration (Cmax) by double, compared to a low-fat breakfast. The bioavailability of the two formulations was very similar, although the sample size was not sufficient to demonstrate bioequivalence because the intraindividual variability of albendazole was approximately 60%.Implications: The higher albendazole and albendazole sulfoxide levels when administered with a high-fat meal could be of importance in clinical practice. Since albendazole labeling recommends its administration with meals, it is necessary to insist on taking it with a fatty meal so that the effectiveness of albendazole is not compromised.

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Ginsenoside Absorption Rate and Extent Enhancement of Black Ginseng (CJ EnerG) over Red Ginseng in Healthy Adults

Pharmaceutics ◽

10.3390/pharmaceutics13040487 ◽

2021 ◽

Vol 13 (4) ◽

pp. 487

Author(s):

Saebyul Yoo ◽

Bom-I Park ◽

Do-hyun Kim ◽

Sooyoung Lee ◽

Seung-hoon Lee ◽

...

Keyword(s):

Clinical Trial ◽

Molecular Weight ◽

Absorption Rate ◽

Systemic Exposure ◽

Red Ginseng ◽

Double Blind ◽

Time Curve ◽

Concentration Time ◽

Black Ginseng ◽

Clinically Significant

Red ginseng (RG) and black ginseng (BG, CJ EnerG) were prepared from fresh ginseng using one and nine cycles of steaming and drying, respectively. This process reduces the molecular weight (MW) of ginsenoside-active compounds in ginseng by removing sugar moieties from their dammaranes. We compared the pharmacokinetic characteristics of ginsenosides between BG comprising mainly low-MW ginsenosides (Rg3, Rg5, Rk1, and Rh1) and RG that predominantly contains high-MW ginsenosides (Rb1, Rb2, Rc, Rd, Re, and Rg1). The safety profiles and tolerability were also studied using a randomized, double-blind, single-dose, crossover clinical trial. A combination of Rb1, Rg1, and Rg3, well-known representative and functional RG components, exhibited a 1-h faster absorption rate (Tmax) and 58% higher exposure (24-h area under the concentration–time curve, AUC24) in BG than in RG. Furthermore, the combination of Rg3, Rg5, and Rk1, the major and most efficient components in BG, displayed 824% higher absorption (AUC24) in BG than in RG. The total ginsenoside showed a 5-h rapid intestinal absorption (Tmax) and 79% greater systemic exposure (AUC24) in BG than in RG. No clinically significant findings were observed in terms of safety or tolerability. Thus, BG extract was more effective than RG extract.

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Pharmacokinetics of Ethambutol under Fasting Conditions, with Food, and with Antacids

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.43.3.568 ◽

1999 ◽

Vol 43 (3) ◽

pp. 568-572 ◽

Cited By ~ 62

Author(s):

Charles A. Peloquin ◽

Amy E. Bulpitt ◽

George S. Jaresko ◽

Roger W. Jelliffe ◽

James M. Childs ◽

...

Keyword(s):

Maximum Concentration ◽

Pharmacokinetic Model ◽

Mass Spectrometry Data ◽

Gas Chromatography Mass Spectrometry ◽

High Fat ◽

Time Curve ◽

First Order ◽

Concentration Time ◽

Males And Females ◽

Fat Meal

ABSTRACT Ethambutol (EMB) is the most frequent “fourth drug” used for the empiric treatment of Mycobacterium tuberculosis and a frequently used drug for infections caused by Mycobacterium avium complex. The pharmacokinetics of EMB in serum were studied with 14 healthy males and females in a randomized, four-period crossover study. Subjects ingested single doses of EMB of 25 mg/kg of body weight under fasting conditions twice, with a high-fat meal, and with aluminum-magnesium antacid. Serum was collected for 48 h and assayed by gas chromatography-mass spectrometry. Data were analyzed by noncompartmental methods and by a two-compartment pharmacokinetic model with zero-order absorption and first-order elimination. Both fasting conditions produced similar results: a mean (± standard deviation) EMB maximum concentration of drug in serum (C max) of 4.5 ± 1.0 μg/ml, time to maximum concentration of drug in serum (T max) of 2.5 ± 0.9 h, and area under the concentration-time curve from 0 h to infinity (AUC0–∞) of 28.9 ± 4.7 μg · h/ml. In the presence of antacids, subjects had a mean C maxof 3.3 ± 0.5 μg/ml, T max of 2.9 ± 1.2 h, and AUC0–∞ of 27.5 ± 5.9 μg · h/ml. In the presence of the Food and Drug Administration high-fat meal, subjects had a mean C max of 3.8 ± 0.8 μg/ml, T max of 3.2 ± 1.3 h, and AUC0–∞ of 29.6 ± 4.7 μg · h/ml. These reductions in C max, delays inT max, and modest reductions in AUC0–∞ can be avoided by giving EMB on an empty stomach whenever possible.

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Effects of a High-Fat Meal on the Relative Oral Bioavailability of Piperaquine

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.49.6.2407-2411.2005 ◽

2005 ◽

Vol 49 (6) ◽

pp. 2407-2411 ◽

Cited By ~ 67

Author(s):

Ing-Kye Sim ◽

Timothy M. E. Davis ◽

Kenneth F. Ilett

Keyword(s):

Oral Bioavailability ◽

Geometric Mean ◽

Pharmacokinetic Analysis ◽

Lipid Solubility ◽

Fasting State ◽

High Fat ◽

Time Curve ◽

Hematological Indices ◽

Concentration Time ◽

Fat Meal

ABSTRACT Piperaquine (PQ) is an antimalarial drug whose high lipid solubility suggests that its absorption can be increased by a high-fat meal. We examined the pharmacokinetics of PQ phosphate (500 mg given orally) in the fasting state and after a high-fat meal in eight healthy Caucasian volunteers (randomized crossover). Plasma PQ concentration-time profiles were analyzed by using noncompartmental pharmacokinetic analysis. In the fed state, the geometric mean C max increased by 213%, from 21.0 to 65.8 μg/liter (P < 0.001). The time of C max was not significantly different between the fasting and fed states. The geometric mean area under the concentration-time curve from zero onward (AUC0-∞) increased by 98%, from 3,724 to 7,362 μg h/liter (P = 0.006). The oral bioavailability of PQ relative to the fasting state was 121% greater after the high-fat meal (95% confidence interval, 26 to 216% increase; P = 0.020). The side effects, postural blood pressure changes, electrocardiographic corrected QT interval, serum glucose, and other biochemical and hematological indices were similar in the fasting and fed states over 28 days of follow-up.

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Pharmacokinetics and Absorption of Posaconazole Oral Suspension under Various Gastric Conditions in Healthy Volunteers

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01034-08 ◽

2008 ◽

Vol 53 (3) ◽

pp. 958-966 ◽

Cited By ~ 222

Author(s):

Gopal Krishna ◽

Allen Moton ◽

Lei Ma ◽

Matthew M. Medlock ◽

James McLeod

Keyword(s):

Proton Pump ◽

Gastric Motility ◽

Nutritional Supplement ◽

Gastric Ph ◽

High Fat ◽

Time Curve ◽

Concentration Time ◽

Dosing Frequency ◽

Randomized Crossover Study ◽

Fat Meal

ABSTRACT A four-part, randomized, crossover study with healthy subjects evaluated the effects of gastric pH, the dosing frequency and prandial state, food consumption timing, and gastric motility on the absorption of posaconazole. In part 1, a single dose (SD) of posaconazole (400 mg) was administered alone or with an acidic beverage or a proton pump inhibitor (PPI), or both. In part 2, posaconazole (400 mg twice daily and 200 mg four times daily) was administered for 7 days with and without a nutritional supplement (Boost). In part 3, an SD of posaconazole (400 mg) was administered while the subjects were fasting and before, during, and after a high-fat meal. In part 4, an SD of posaconazole (400 mg) and the nutritional supplement were administered alone, with metoclopramide, and with loperamide. Compared to the results obtained with posaconazole alone, administration with an acidic beverage increased the posaconazole maximum concentration in plasma (C max) and the area under the concentration-time curve (AUC) by 92% and 70%, respectively, whereas a higher gastric pH decreased the posaconazole C max and AUC by 46% and 32%, respectively. Compared to the results obtained with posaconazole alone, posaconazole at 400 mg or at 200 mg plus the nutritional supplement increased the posaconazole C max and AUC by 65% and 66%, respectively, and by up to 137% and 161%, respectively. Administration before a high-fat meal increased the C max and the AUC by 96% and 111%, respectively, while administration during and after the meal increased the C max and the AUC by up to 339% and 387%, respectively. Increased gastric motility decreased the C max and the AUC by 21% and 19%, respectively. Strategies to maximize posaconazole exposure in patients with absorption difficulties include administration with or after a high-fat meal, with any meal or nutritional supplement, with an acidic beverage, or in divided doses and the avoidance of proton pump inhibitors.

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Maximally Tolerated Busulfan Area Under the Concentration-Time Curve (AUC) In Combination with Fludarabine as Conditioning Prior to Allogeneic Hematopoietic Cell Transplantation.

Blood ◽

10.1182/blood.v116.21.3499.3499 ◽

2010 ◽

Vol 116 (21) ◽

pp. 3499-3499

Author(s):

Janelle Perkins ◽

Teresa Field ◽

Jongphil Kim ◽

Hugo F. Fernandez ◽

Lia Perez ◽

...

Keyword(s):

Cell Transplantation ◽

Cumulative Incidence ◽

Research Funding ◽

Hematopoietic Cell Transplantation ◽

Systemic Exposure ◽

Hematopoietic Cell ◽

Time Curve ◽

Concentration Time ◽

Gvhd Prophylaxis ◽

Dose Limiting Toxicity

Abstract Abstract 3499 Intravenous busulfan (IV Bu) dosing in hematopoietic cell transplantation (HCT) conditioning regimens has been based largely on bioequivalence studies done with the oral dosage form. As systemic exposure to Bu has been correlated to both efficacy and toxicity, we used area under the concentration-time curve (AUC) to prospectively determine the maximally tolerated systemic exposure to IV Bu when given daily in combination with fludarabine as HCT conditioning. Three AUC levels were planned: 6000, 7500, and 9000 micromole*min/L, in cohorts of 20 patients (pts) each, with an additional 10 pts to be enrolled at the maximally tolerated AUC. To be included, pts had be 16–65 years old and have a hematologic malignancy, an HLA A, B, C, DRB1 8/8 or 7/8 matched related or unrelated donor, Karnofsky performance status 70–100%, and adequate organ function. The initial dose of IV Bu for the first AUC level was 170mg/m2/day on day -6 and day -5 then, on day -4 and day -3 doses were adjusted based on pharmacokinetic modeling after the first dose to achieve an average daily AUC of 6000. First doses for the subsequent cohorts were based on the linear correlation between AUC and dose in the previous cohort: 180mg/m2/day for AUC 7500 and 220mg/m2/day for AUC 9000, with dose adjustment on days -4 and -3 as described. Pharmacokinetic analysis was done after the day -3 dose to verify the accuracy of the dose adjustments. The first 20 pts in the AUC 6000 cohort (DL1) were coenrolled onto a randomized trial of GVHD prophylaxis (tacrolimus and methotrexate vs tacrolimus and mycophenolate mofetil) and were analyzed separately from a second cohort of 20 pts receiving an AUC 6000 (DL1A) and GVHD prophylaxis with tacrolimus and methotrexate. 20 pts were then enrolled onto AUC 7500 (DL2), followed by 3 pts on AUC 9000 (DL3). All DL3 pts had dose limiting toxicity so accrual to that level was stopped. An additional 9 pts have been treated to date on DL2 (5 of these are <100 days posttransplant and are not evaluable for toxicity or GVHD). The median (and range) average daily AUC for each of the cohorts were: DL1 5955 (5375-6557); DL1A 6145 (4846-7018); DL2 7555 (5920-8682); DL3 8899 (8784-8955). There were no primary engraftment failures and median times to neutrophil engraftment were: DL1 15 days, DL1A 16 days, DL2 14 days, and DL3 12 days (p=0.01). The dose-limiting toxicity seen at DL3 was hepatic venoocclusive disease (VOD) which developed in all 3 pts; two of these pts died. There were no seizures attributable to IV Bu seen at any dose level. NCI CTCAE toxicities (observed in the first 100 days unrelated to infection or GVHD) that were significantly different between the dose level groups were dermatitis and VOD with more severe toxicity seen in DL2 and DL3. Diarrhea and the use of total parenteral nutrition appeared to be more common on DL2 and DL3 but not significantly so. The cumulative incidence of acute GVHD was similar across the cohorts (p=0.11). There was no difference between the dose levels in cumulative incidence of relapse (p=0.54) or event-free survival (p=0.4). Nonrelapse mortality at 6 months was significantly different: DL1 20%, DL1A 0%, DL2 17.5% and DL3 67% (p=0.008) as was overall survival at 6 months: DL1 75%, DL1A 90%, DL2 80%, DL3 33% (p=0.04). We conclude that in the pts studied, 7500 micromole*min/L is the maximally tolerated AUC based on protocol-defined criteria but exceeding an AUC of 6000 may not provide any survival benefit. Disclosures: Perkins: PDL BioPharma: Research Funding. Off Label Use: IV busulfan was used in combination with fludarabine as conditioning prior to allogeneic hematopoietic cell transplantation in patients with a variety of hematologic malignancies. Field:PDL BioPharma: Research Funding.

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The Relative Bioavailability, Food Effect and Drug Interaction With Omeprazole Of Momelotinib Tablet Formulation

Blood ◽

10.1182/blood.v122.21.5239.5239 ◽

2013 ◽

Vol 122 (21) ◽

pp. 5239-5239

Author(s):

Yan Xin ◽

Lixin Shao ◽

Wei Deng ◽

Amanda Shaffer ◽

Pharm D ◽

...

Keyword(s):

Small Molecule ◽

Phase 1 ◽

Relative Bioavailability ◽

Reducing Agent ◽

High Fat ◽

Employment Equity ◽

Molecule Inhibitor ◽

Effect Of Food ◽

Equity Ownership ◽

Dose Proportional

Abstract Background Momelotinib (MMB, previously CYT387) is a potent and selective small molecule inhibitor of JAK 1 and JAK 2, and is currently under investigation for the treatment of myelofibrosis (MF). In a Phase 1/2 study of patients with MF, the 300 mg capsule administered once daily was selected as the Phase 3 dose based on a favorable benefit:risk profile. An immediate release tablet formulation (MMB tablet) with better thermodynamic stability and similar biopharmaceutical properties as the capsule formulation (MMB capsule) was developed. The relative bioavailability of MMB tablet vs capsule, effect of food on MMB tablet pharmacokinetics (PK), and the effect of omeprazole on MMB tablet PK were evaluated in a Phase 1 study. Methods The MMB tablet (dose: 100 to 300 mg) vs MMB capsule PK (300 mg) was evaluated in a Phase 1, single dose study in healthy subjects. MMB tablet PK at supratherapeutic doses (up to 800 mg), under fed and fasted conditions, and with an acid reducing agent (i.e.,. omeprazole) was also evaluated. Intensive PK and PD sampling occurred from 0.5 hour up to 36 hours post dose. Safety was monitored throughout the study. A parametric analysis of variance (ANOVA) using a mixed-effects model was used to fit to the natural logarithmic transformation of PK parameters (AUC and Cmax). The 90% confidence intervals were constructed for the ratio of geometric means of MMB tablet PK at 100, 150, 200 and 300 mg vs MMB capsule 300 mg, using equivalence bounds of 70% to 143% for AUC and Cmax. A similar approach was used to assess the effect of food or omeprazole. MMB tablet PK at supratherapeutic doses of 400 mg and 800 mg were also evaluated. Results MMB tablet provided plasma exposures that were less-than dose-proportional from 100 mg to 800 mg (Figure 1). MMB tablet at 200 mg provided plasma exposures that were equivalent to MMB capsule at 300 mg (Table 1). Intake of light and high-fat meal modestly increased Cmax (38% and 28% increase for light and high-fat meals, respectively) and AUCinf (16% and 28% increase for light and high-fat meals, respectively) for MMB tablet. Omeprazole reduced the exposure of MMB tablet by 36% for Cmax and 31% for AUCinf. These differences were not considered clinically relevant. Conclusion MMB tablet at 200 mg provides comparable exposure to MMB capsule at 300 mg. MMB tablet plasma exposures increased in a less than dose-proportional manner. No clinically relevant effects of food or acid reducing agent were observed on MMB tablet PK. Disclosures: Xin: Gilead Sciences: Employment. Off Label Use: GS-9820 is a second-generation, selective, small molecule inhibitor of PI3Kƒ’ƒn under investigation for the treatment of lymphoid malignancies including non-Hodgkin¡¦s lymphoma (NHL) and chronic lymphocytic leukemia (CLL). Shao:Gilead Sciences: Employment, Equity Ownership. Deng:Gilead Sciences: Employment, Equity Ownership. Shaffer:Gilead Sciences: Employment. Stefanidis:Gilead Sciences: Employment. Hemenway:Gilead Sciences: Employment. Li:Gilead Sciences: Employment, Equity Ownership. Jun:Gilead Sciences: Employment, Equity Ownership. Ramanathan:Gilead Sciences: Employment, Equity Ownership.

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0745 The Pharmacokinetics of FT218, Once Nightly Sodium Oxybate: Food Effect and Bioavailability Compared to Twice Nightly Sodium Oxybate

SLEEP ◽

10.1093/sleep/zsaa056.741 ◽

2020 ◽

Vol 43 (Supplement_1) ◽

pp. A283-A283

Author(s):

M Thorpy ◽

D Seiden ◽

J Grassot ◽

D Monteith ◽

J Dubow ◽

...

Keyword(s):

Single Dose ◽

Controlled Release ◽

Food Effect ◽

Relative Bioavailability ◽

Sodium Oxybate ◽

Pharmacokinetic Studies ◽

Release Formulation ◽

Fed State ◽

Fasted State ◽

Bioavailability Study

Abstract Introduction Sodium oxybate is an effective treatment for excessive daytime sleepiness and cataplexy in patients with narcolepsy. The FDA approved formulation requires twice-nightly dosing; at bedtime and 2.5 - 4 hours later. FT218 is a controlled-release formulation of sodium oxybate intended for once-nightly dosing, using Avadel’s proprietary Micropump™ technology. The objective of this study was to evaluate the relative bioavailability of investigational once-nightly sodium oxybate, FT218, 6 g, compared to commercially available twice-nightly sodium oxybate and the food effect of FT218. Methods Two crossover, single-dose pharmacokinetic studies were conducted in healthy volunteers. The first, a relative bioavailability study (n=28) was completed comparing FT218 6 g to twice-nightly sodium oxybate 6 g (in two divided doses of 3 g). The second, evaluated the food effect (n=16) of FT218 6g in the Fed vs. Fasted state. Results FT218 had a lower overall Cmax than twice-nightly sodium oxybate, while AUC was equivalent. C8h level and variability was comparable between FT218 and twice-nightly sodium oxybate. In the Fed, compared to the Fasted state, FT218 had a longer Tmax, lower Cmax and decreased AUC (Cmax 67%, AUC 86%, Tmax 1-hour slower than Fasted values). Adverse Events with FT218 were mostly mild or moderate in severity, non-serious and known AEs associated with sodium oxybate. The safety profiles of FT218 and twice-nightly sodium oxybate at 6 g appeared similar. Conclusion Once-nightly FT218 at 6 g demonstrated a lower overall Cmax and similar exposure to twice-nightly sodium oxybate, with similar C8h plasma levels and C8h variability. In the Fed state, AUC and Cmax of FT218 was lower than in the Fasted State. FT218 was generally safe and well tolerated and the safety profile appeared comparable to twice-nightly sodium oxybate. Support This work was supported by Avadel Pharmaceuticals.

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