Part Two: Pharmacokinetic Evaluation of E-Liquid Flavors of Vuse Solo Electronic Nicotine Delivery System, An Unblinded, Parallel, Randomized Study To Assess Nicotine Uptake In Smokers

Abstract This paper reports the findings of a randomized nicotine pharmacokinetic (PK) study of a closed electronic nicotine delivery system (ENDS). The study evaluated four flavor variants of Vuse Solo ENDS where subjects used their randomized investigational product (IP) for 10 minutes ad libitum and blood samples were collected for PK assessments that included maximum plasma nicotine concentration (Cmax) and area under the nicotine concentration-vs-time curve up to 60 minutes (AUCnic0–60). Baseline-adjusted mean Cmax ranged from 6.53 to 8.21 ng/mL, and mean AUCnic0–60 ranged from 206.87 to 263.52 ng*min/mL for all ENDS IPs. Results for Cmax and AUCnic0-60 values were consistent among the ENDS IP flavor variants tested and results indicate that flavors did not affect nicotine uptake in human subjects.

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Variable Voltage, Tank-Style ENDS Do Not Always Deliver Nicotine

Tobacco Regulatory Science ◽

10.18001/trs.6.6.5 ◽

2020 ◽

Vol 6 (6) ◽

pp. 416-422

Author(s):

Alisha Eversole ◽

Sarah Maloney ◽

Soha Talih ◽

Rola Salman ◽

Nareg Karaoghlanian ◽

...

Keyword(s):

Delivery System ◽

Cigarette Smokers ◽

Nicotine Concentration ◽

Men 2 ◽

Nicotine Delivery ◽

Plasma Nicotine ◽

Variable Voltage ◽

Ad Libitum ◽

Performance Heterogeneity

Objectives: In this paper, we characterize the nicotine delivery profile of a variable voltage, tank-style electronic nicotine delivery system (ENDS). Methods: Ten cigarette smokers (8 men, 2 women) completed this within-subject study assessing effects of 2 device power settings (15 W, 45 W) and 3 liquid nicotine concentrations (0, 3, and 6 mg/ml) using a tank-style ENDS. Participants completed one directed (10 puffs) and one ad libitum use period for each condition, with blood sampled throughout. Results: Plasma nicotine concentration did not increase significantly at 15 W regardless of liquid nicotine concentration. At 45 W, mean plasma nicotine increased (not significantly compared to 0 mg/ml) from 2.24 ng/ml (SD = 0.2) at baseline to 3.4 ng/ml (SD = 0.6) in the 3 mg/ml condition. In the 6 mg/ml, 45 W condition, mean plasma nicotine increased significantly (compared to 0 mg/ml) from 2.0 ng/ml (SD=0) at baseline to 5.96 ng/ml (SD = 1.3) after 10 puffs. In general, puf duration and volume decreased as device power and nicotine concentration increased. Conclusions: Despite using a variable wattage, tank-style device, nicotine delivery was minimal. These results, when combined with results from other studies using tank-style devices, highlight ENDS performance heterogeneity. Regulation may play a role in standardizing ENDS nicotine delivery.

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Enhanced Bioavailability of AC1497, a Novel Anticancer Drug Candidate, via a Self-Nanoemulsifying Drug Delivery System

Pharmaceutics ◽

10.3390/pharmaceutics13081142 ◽

2021 ◽

Vol 13 (8) ◽

pp. 1142

Author(s):

Kshitis Chandra Baral ◽

Jae-Geun Song ◽

Sang Hoon Lee ◽

Rajiv Bajracharya ◽

Godesi Sreenivasulu ◽

...

Keyword(s):

Drug Delivery ◽

Plasma Concentration ◽

Drug Delivery System ◽

Delivery System ◽

Cancer Metabolism ◽

Oral Absorption ◽

Drug Candidate ◽

Maximum Plasma ◽

Time Curve ◽

Dual Inhibitor

AC1497 is an effective dual inhibitor of malate dehydrogenase 1 and 2 targeting cancer metabolism. However, its poor aqueous solubility results in low bioavailability, limiting its clinical development. This study was conducted to develop an effective self-nanoemulsifying drug delivery system (SNEDDS) of AC1497 to improve its oral absorption. Based on the solubility of AC1497 in various oils, surfactants, and cosurfactants, Capryol 90, Kolliphor RH40, and Transcutol HP were selected as the components of SNEDDS. After testing various weight ratios of Capryol 90 (20–30%), Kolliphor RH40 (35–70%), and Transcutol HP (10–35%), SNEDDS-F4 containing 20% Capryol 90, 45% Kolliphor RH40, and 35% Transcutol HP was identified as an optimal SNEDDS with a narrow size distribution (17.8 ± 0.36 nm) and high encapsulation efficiency (93.6 ± 2.28%). Drug release from SNEDDS-F4 was rapid, with approximately 80% of AC1497 release in 10 min while the dissolution of the drug powder was minimal (<2%). Furthermore, SNEDDS-F4 significantly improved the oral absorption of AC1497 in rats. The maximum plasma concentration and area under the plasma concentration–time curve of AC1497 were, respectively 6.82- and 3.14-fold higher for SNEDDS-F4 than for the drug powder. In conclusion, SNEDDS-F4 with Capryol 90, Kolliphor RH40, and Transcutol HP (20:45:35, w/w) effectively improves the solubility and oral absorption of AC1497.

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Correction to: An exploratory non-randomized study of a 3-month electronic nicotine delivery system (ENDS) intervention with people accessing a homeless supported temporary accommodation service (STA) in Ireland

Harm Reduction Journal ◽

10.1186/s12954-021-00549-6 ◽

2021 ◽

Vol 18 (1) ◽

Author(s):

Florian Scheibein ◽

Kevin McGirr ◽

Andy Morrison ◽

Warren Roche ◽

John Stephen Gary Wells

Keyword(s):

Delivery System ◽

Randomized Study ◽

Nicotine Delivery ◽

Temporary Accommodation

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Supplemental Material for The Interaction of Nicotine Concentration and Device Power on Electronic Nicotine Delivery System (ENDS) Abuse Liability Among Exclusive ENDS Users and Dual Users of ENDS and Combustible Cigarettes

Experimental and Clinical Psychopharmacology ◽

10.1037/pha0000523.supp ◽

2021 ◽

Keyword(s):

Delivery System ◽

Abuse Liability ◽

Nicotine Concentration ◽

Nicotine Delivery

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Acute effects of JUUL and IQOS in cigarette smokers

Tobacco Control ◽

10.1136/tobaccocontrol-2019-055475 ◽

2020 ◽

pp. tobaccocontrol-2019-055475 ◽

Cited By ~ 5

Author(s):

Sarah Maloney ◽

Alisha Eversole ◽

Melanie Crabtree ◽

Eric Soule ◽

Thomas Eissenberg ◽

...

Keyword(s):

Carbon Monoxide ◽

Laboratory Study ◽

Subjective Effects ◽

Acute Effects ◽

Subjective Experiences ◽

Cigarette Smokers ◽

Nicotine Concentration ◽

Nicotine Delivery ◽

Plasma Nicotine ◽

Ad Libitum

BackgroundJUUL is an electronic cigarette that aerosolises a nicotine-containing liquid, while IQOS heats tobacco to produce an aerosol. Both are marketed to smokers, but their effects have seldom been examined in this population.MethodsEighteen cigarette smokers (13 men) with no JUUL or IQOS experience completed a within-subject, laboratory study assessing nicotine delivery and subjective effects after controlled (10 puffs, ~30 s interpuff interval) and ad libitum (90 min) use of JUUL, IQOS or own-brand (OB) cigarettes.ResultsJUUL increased mean plasma nicotine concentration significantly from 2.2 (SD=0.7) ng/mL to 9.8 (4.9) ng/mL after 10 puffs and to 11.5 (9.3) ng/mL after ad libitum use. IQOS increased mean plasma nicotine significantly from 2.1 (0.2) ng/mL to 12.7 (6.2) ng/mL after 10 puffs and to 11.3 (8.0) ng/mL after ad libitum use. OB increased mean plasma nicotine significantly from 2.1 (0.2) ng/mL to 20.4 (11.4) ng/mL after 10 puffs and to 21.0 (10.2) ng/mL after ad libitum use. Mean OB plasma nicotine concentration was significantly higher than JUUL and IQOS. OB increased expired carbon monoxide concentration, but IQOS and JUUL did not. ‘Craving a cigarette/nicotine’ and ‘Urges to smoke’ were reduced significantly for all products following the directed bout.ConclusionsAmong smokers, JUUL and IQOS delivered less nicotine than cigarettes. Also, in this sample, IQOS and OB reduced abstinence symptoms more effectively than JUUL. Additional work with experienced JUUL and IQOS users is needed, as their nicotine delivery profiles and subjective experiences may differ.

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Adolescent Clinical Development of Ezogabine/Retigabine as Adjunctive Therapy for Partial-Onset Seizures: Pharmacokinetics and Tolerability

The Journal of Pediatric Pharmacology and Therapeutics ◽

10.5863/1551-6776-21.5.404 ◽

2016 ◽

Vol 21 (5) ◽

pp. 404-412 ◽

Cited By ~ 1

Author(s):

Debra J. Tompson ◽

Mauro Buraglio ◽

Susan M. Andrews ◽

James W. Wheless

Keyword(s):

Adjunctive Therapy ◽

Small Sample Size ◽

Venous Blood ◽

Plasma Concentrations ◽

Small Sample ◽

Maximum Plasma ◽

Open Label ◽

Time Curve ◽

Blood Samples ◽

Finger Prick

OBJECTIVES: To explore the pharmacokinetic (PK) profile and safety of ezogabine (EZG)/retigabine (RTG) as adjunctive therapy for uncontrolled partial-onset seizures (POS) in adolescents. METHODS: In this multiple-dose study (NCT01494584), adolescents with POS received EZG/RTG immediate-release tablets three times daily (TID) as adjunctive therapy to 1 to 3 concurrent antiepileptic drugs. The study comprised a screening phase, and a 5- to 8-week treatment phase starting with 100 mg TID up-titrated once weekly by ≤50 mg TID to a maximum dosage of 300 mg TID. There were 8 venous blood samples and 2 finger-prick blood samples collected for PK analysis during 8-hour time periods at the target dosages of 100, 200, and 300 mg TID. RESULTS: This study was terminated prematurely on US Food and Drug Administration advice due to pigmentation/discoloration findings in long-term, open-label extension studies in adults. Five participants (ages 13–16 years) had enrolled in the study. For the EZG/RTG 100-, 200-, and 300-mg doses, the area under the concentration-time curve during the dosage intervals was 1680, 2559, and 3784 ng/hr/mL; maximum plasma concentrations were 370, 536, and 751 ng/mL, and minimum plasma concentrations were 105, 200, and 287 ng/mL, respectively. Venous and finger-prick concentrations of EZG/RTG were similar. No significant adverse events were observed during treatment (133–213 days). CONCLUSIONS: EZG/RTG PK appeared linear across the dosage range of 100 to 300 mg TID in adolescents with POS, and were consistent with adult observations. The small sample size and short study duration preclude conclusions regarding the safety and efficacy of EZG/RTG.

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The interaction of nicotine concentration and device power on electronic nicotine delivery system (ENDS) abuse liability among exclusive ENDS users and dual users of ENDS and combustible cigarettes.

Experimental and Clinical Psychopharmacology ◽

10.1037/pha0000523 ◽

2021 ◽

Author(s):

Cosima Hoetger ◽

Rose S. Bono ◽

Augustus M. White ◽

Andrew J. Barnes ◽

Caroline O. Cobb

Keyword(s):

Delivery System ◽

Abuse Liability ◽

Nicotine Concentration ◽

Nicotine Delivery

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Roles of Leptin and Ghrelin in the Loss of Body Weight Caused by a Low Fat, High Carbohydrate Diet

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2002-021262 ◽

2003 ◽

Vol 88 (4) ◽

pp. 1577-1586 ◽

Cited By ~ 123

Author(s):

David S. Weigle ◽

David E. Cummings ◽

Patricia D. Newby ◽

Patricia A. Breen ◽

R. Scott Frayo ◽

...

Keyword(s):

Weight Loss ◽

Body Weight ◽

Dietary Fat ◽

Human Subjects ◽

Energy Restriction ◽

Low Fat ◽

Time Curve ◽

Dietary Energy Restriction ◽

Ad Libitum ◽

Plasma Leptin

Loss of body fat by caloric restriction is accompanied by decreased circulating leptin levels, increased ghrelin levels, and increased appetite. In contrast, dietary fat restriction often decreases adiposity without increasing appetite. Substitution of dietary carbohydrate for fat has been shown to increase the area under the plasma leptin vs. time curve (AUC) over the course of 24 h. This effect, if sustained, could explain the absence of a compensatory increase in appetite on a low fat diet. To clarify the effect of dietary fat restriction on leptin and ghrelin, we measured AUC for these hormones in human subjects after each of the following sequential diets: 2 wk on a weight-maintaining 35% fat (F), 45% carbohydrate (C), 20% protein (P) diet (n = 18); 2 wk on an isocaloric 15% F, 65% C, 20% P diet (n = 18); and 12 wk on an ad libitum 15% F, 65% C, 20% P diet (n = 16). AUC for leptin was similar on the isocaloric 15% F and 35% F diets (555 ± 57 vs. 580 ± 56 ng/ml·24 h; P = NS). Body weight decreased from 74.6 ± 2.4 to 70.8 ± 2.7 kg on the ad libitum 15% F diet (P < 0.001) without compensatory increases in food consumption or AUC for ghrelin. Proportional amplitude of the 24-h leptin profile was increased after 12 wk on the 15% fat diet. We conclude that weight loss early in the course of dietary fat restriction occurs independently of increased plasma leptin levels, but that a later increase in amplitude of the 24-h leptin signal may contribute to ongoing weight loss. Fat restriction avoids the increase in ghrelin levels caused by dietary energy restriction.

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Nicotine delivery and user reactions to Juul EU (20 mg/ml) compared with Juul US (59 mg/ml), cigarettes and other e-cigarette products

Psychopharmacology ◽

10.1007/s00213-020-05734-2 ◽

2020 ◽

Author(s):

Anna Phillips-Waller ◽

Dunja Przulj ◽

Katie Myers Smith ◽

Francesca Pesola ◽

Peter Hajek

Keyword(s):

Pharmacokinetic Profile ◽

Crossover Design ◽

Subjective Ratings ◽

Blood Samples ◽

Nicotine Concentration ◽

Within Subjects ◽

Ad Libitum ◽

The Difference ◽

User Ratings ◽

The Eu

Abstract Rationale The degree to which the EU version of Juul with 20 mg/ml nicotine (Juul EU) delivers nicotine to users is likely to determine its treatment potential. Objectives To compare the pharmacokinetic profile and user ratings of Juul EU, Juul US (59 mg/ml nicotine), cigarettes and other e-cigarette (EC) products. Methods In a within-subjects crossover design, 18 vapers used, at separate sessions, their own brand cigarette (OBC), Juul US and Juul EU for 5 min ad libitum, after overnight abstinence. Seven of the participants also tested eight other EC previously. Blood samples were taken at baseline and 2, 4, 6, 8, 10 and 30 min after initiating product use. Products were rated on a range of characteristics. Results Juul EU delivered less nicotine than OBC (t(13) = −4.64 p < .001) and than Juul US (t(13) = −6.40, p < .001): AUC0 ≥ 30 77.3, 324.8 and 355.9, respectively. Maximum nicotine concentration (Cmax) was also much lower for Juul EU than Juul US (z = −3.59, p < .001): Cmax 3.8 ng/ml vs 21.1 ng/ml, respectively. Juul EU was perceived to relieve urges to smoke less than Juul US (z = −2.29, p = .022) and to provide less nicotine (z = −2.57. p = 0.010). Juul EU delivered less nicotine than refillable EC (Cmax: t(6) = 3.02, p = 0.023; AUC0 ≥ 30: z = −2.20, p = 0.028) and also less than cig-a-like EC, though the difference did not reach significance (Cmax: t(6) = 2.49, p = 0.047; AUC0 ≥ 30: z = −1.99, p = 0.046). Subjective ratings of Juul EU and other EC products were similar. Conclusions Juul EU delivers much less nicotine to users than Juul US, and also less than refillable EC products. It may thus have more limited potential to help smokers quit.

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