Original Contribution

Journal of Cosmetic Dermatology, 14, 33--39

A phase 1 pharmacokinetic study of ATX-101: serum lipids and

adipokines following synthetic deoxycholic acid injections
Patricia Walker, MD, PhD,1,2,* & Daniel Lee, MS3,*
1
Private Practice, Carpinteria, CA, USA
2
Chief Medical Officer, Kythera Biopharmaceuticals, Inc., Calabasas, CA, USA
3
Clinical Affairs, Kythera Biopharmaceuticals, Inc., Calabasas, CA, USA

Summary Background ATX-101 (deoxycholic acid injection, Kythera Biopharmaceuticals, Inc.) is

a proprietary formulation of pure synthetic deoxycholic acid (DCA). It is undergoing
clinical investigation as an injectable drug for contouring the submental area by
reducing submental fat (SMF). When injected into subcutaneous fat, ATX-101 causes
focal adipocytolysis, the targeted destruction of fat cells.
Objectives This phase 1 study evaluated the safety, pharmacokinetics (PK), and
pharmacodynamic effects of ATX-101 (100-mg total dose).
Methods Following PK evaluation of baseline endogenous DCA, lipids, and adipokines
in the initial stage of the study (samples collected at hours 0.25, 0.5, 1, 1.5, 2, 4, 6,
12, 15.5, and 24.5), 10 subjects received subcutaneous injections of ATX-101 into
abdominal fat. PK evaluation of DCA, lipids, and adipokines was repeated in the
second phase of the study.
Results After ATX-101 injections, plasma concentration of DCA increased
transiently, reached a maximum plasma concentration rapidly, and returned to
endogenous concentrations within 12 h postdose. ATX-101 injection was not
associated with any clinically meaningful changes in systemic concentrations of
total cholesterol, total triglycerides, free fatty acids, C-reactive protein, or
interleukin-6. Adverse events were mild in severity, transient, and showed a
temporal relationship to dosing.
Conclusions This study demonstrated favorable safety and PK profiles, and no
clinically meaningful changes in DCA, lipids, and proinflammatory cytokines
following subcutaneous injection of ATX-101. Our results support continued clinical
investigation of ATX-101 as an injectable drug to reduce SMF.
Keywords: adipokines, ATX-101, deoxycholic acid, lipids, pharmacokinetics, submen-
tal fat

Correspondence: Daniel Lee, MS, Senior Director, Clinical Affairs, Kythera
Biopharmaceuticals, Inc., 30930 Russell Ranch Road, 3rd Floor, West-
lake Village, CA 91362, USA. E-mail: dlee@kytherabiopharma.com
*Not a current employee of Kythera Biopharmaceuticals, Inc.
Study site: Cetero Research, 4801 Amber Valley Parkway, Fargo, ND, USA
Accepted for publication September 11, 2014
Introduction
Fat accumulation under the chin (submental fat; SMF)
may result in undesirable submental convexity and full-
ness. As a result, individuals may have negative percep-
tions of their overall facial attractiveness and feel a
diminished sense of well-being and satisfaction with
their appearance.1–4 Currently, treatment options for

© 2015 Wiley Periodicals, Inc. 33

ATX-101 and lipid pharmacodynamics . P. Walker & D. Lee
those dissatisfied with their appearance because of
unwanted SMF are primarily surgical, with the tech-
nique based on patient’s presentation and treatment
goals.3,5 Surgical procedures are invasive and associated
with known risks of anesthesia, infection, bleeding,
bruising, and scarring. They are generally associated
with long recovery times, which some patients may con-
sider to be unacceptably inconvenient.4,6
ATX-101 (deoxycholic acid injection) is an injectable
drug, currently undergoing clinical development by
Kythera Biopharmaceuticals, Inc. (Calabasas, CA,
USA), which may provide a nonsurgical and less inva-
sive alternative for contouring the submental area
through the reduction of SMF. ATX-101 is a proprie-
tary formulation of pure, synthetic deoxycholic acid
(DCA). Deoxycholic acid is a tightly regulated, well-
characterized, endogenous bile acid that emulsifies and
solubilizes dietary fat.7,8 When injected subcutane-
ously, DCA physically disrupts the cell membranes of
adipocytes causing focal adipocytolysis, the targeted
destruction of fat cells, as shown by in vivo and in vitro
studies.9–11 The cytolytic activity of DCA is attenuated
by albumin and tissue-associated protein; therefore,
when injected into subcutaneous fat tissue, nearby rel-
atively protein-rich tissues, such as skin, muscle, and
blood vessels, remain largely unaffected, a feature that
may contribute to an enhanced safety margin.11 As
shown in previous studies, injection of DCA and the
resultant adipocytolysis elicits a mild and local inflam-
matory response in which macrophages are attracted
to the area; natural processes then eliminate cellular
debris and liberated lipids.11,12 Whether adipokines
(proinflammatory cytokine profiles) are altered or
whether triglycerides, cholesterol, and free fatty acids
(FFA) enter the bloodstream in clinically meaningful
amounts following DCA-induced adipocytolysis is a
focus of the current study.
The objectives of this trial were to (1) evaluate the
safety and tolerability of subcutaneous injections of
ATX-101 and (2) characterize the pharmacokinetic
(PK) and pharmacodynamic (PD) profiles of circulating
DCA, lipids, and adipokine levels following subcutane-
ous injections of ATX-101 into abdominal fat.
Materials and methods
Subjects
Ten subjects were enrolled in this single-center, open-
label, phase 1 study (ClinicalTrials.gov identifier
NCT01319916). The study was conducted in compli-
ance with the International Conference on Harmonisa-
34
tion Guidelines for Good Clinical Practice and the
United States Code of Federal Regulations for Good
Clinical Practice, and with the principles set forth in
the Declaration of Helsinki. All subjects provided writ-
ten informed consent.
Primary inclusion criteria included the following: (1)
healthy nonsmokers; (2) males or nonpregnant, non-
lactating females; (3) aged 18–65 years; (4) body mass
index (BMI) of 18.5 to ≤30.0 kg/m2; (5) stable weight
(approximately 10 lb) for 3 months before enroll-
ment; (6) normal fasting levels of glucose (75–
100 mg/dL), hemoglobin A1c (4–5.9%), triglycerides
(<150 mg/dL), and cholesterol (<200 mg/dL) for
28 days prior to ATX-101 administration; and (7) neg-
ative hepatitis B, hepatitis C, and human immunodefi-
ciency virus test results.
Primary exclusion criteria included the following: (1)
history of treatment associated with the abdominal
area that, in the investigator’s judgment, could affect
the evaluation of safety; (2) active diet, caloric restric-
tions, or attempt to lose weight; (3) blood donation of
500 mL or blood transfusion within 60 days of study
initiation; (4) plasma donation within 7 days of ATX-
101 administration; (5) diagnosis of lipidosis such as
Gaucher, Niemann-Pick, or Fabry disease, or other
confounding metabolic diseases; (6) history of hypertri-
glyceridemia (>200 mg/dL), hypercholesterolemia
(>240 mg/dL), hyperlipidemia, diabetes, or any other
medical condition that could interfere with laboratory
or safety assessments, or study procedures; (7) use of
statins or other lipid-lowering agents within 28 days of
the start of the study; (8) use of antiglycemic agent at
any time before screening; (9) use of any medication
resulting in systemic exposure during the screening
period; and (10) oral anticoagulant treatment within
10 days before the first study day.
Procedures
The study was conducted in two stages: the first to
establish the baseline endogenous levels of DCA, lipids,
and adipokines; and the second for evaluation of the
effect of ATX-101 on these measures. In the first stage,
subjects were admitted to the research facility for 48 h
to collect baseline data. Endogenous profiles for lipids,
adipokines, and the PK profile for DCA were estab-
lished under controlled dietary conditions on day 0.
Samples for determining concentration baseline levels
of DCA and lipids were collected at hours 0.25, 0.5, 1,
1.5, 2, 4, 6, 12, 15.5, and 24.5. Fasting overnight
continuing until hour 12, and controlled dietary condi-
tions thereafter were observed. Samples for determining
© 2015 Wiley Periodicals, Inc.

adipokine levels were taken once immediately after
subjects were admitted to the research facility and
again 12 h after the standardized meal. The overall
length of the fasting period employed for both the base-
line and post-treatment periods to achieve a stable
baseline for lipid test result observations was approxi-
mately 18–20 h.
For the second stage, subjects were readmitted to the
research facility at least 3 days, but no more than
10 days after completion of stage 1. On day 0 of stage
2, ATX-101 was administered following an overnight,
predosing 12-h fast. A 100-mg total dose of ATX-101
(2 mg/cm2) was injected subcutaneously into abdomi-
nal adipose tissue using a 30-gauge needle. Fifty 0.2-
mL injections were placed 1 cm apart using a grid to
ensure even distribution across the treatment area. At
the discretion of the investigator, ice and/or preinjec-
tion topical anesthesia could have been applied over
the treatment area. The dosing requirements for this
study are the same as those employed in controlled
trials evaluating ATX-101 in SMF.
Postdose samples were collected at the same time
points as in the first stage and performed at approxi-
mately the same time of day to avoid diurnal variation.
For determining DCA and concentrations of lipid levels,
samples were collected at hours 0.25, 0.5, 1, 1.5, 2, 4,
6, 12, 15.5, and 24.5 (fasting until hour 12 and
controlled dietary conditions thereafter). Samples for
determining adipokine levels were taken once immedi-
ately after subjects were admitted to the research facil-
ity before the initiation of the overnight fast and again
12 h after the standardized meal. Additional blood
samples for safety laboratory determination of chemis-
try and hematology were collected at days 3, 7, 14,
21, and 28 postdose.
Pharmacokinetic and pharmacodynamic assessments
PK and PD analyses included DCA, lipids (total trigly-
cerides, total cholesterol, diacylglycerol [DAG], and
FFA) and adipokine profiles (C-reactive protein [CRP],
interleukin [IL]-1a, IL-1b, IL-6, IL-15, interferon
gamma [IFN-c], tumor necrosis factor [TNF-a], adipo-
nectin, apolipoprotein B, insulin, leptin, and resistin).
For DAG, DCA, and adipokines, samples were collected,
cooled, and centrifuged for 10 min. Plasma samples
were transferred into duplicate or triplicate polypropyl-
ene tubes, maintained in an ice bath and subsequently
stored at –70 °C (20 °C; for DAG and adipokines) or
–20 °C (10 °C; for DCA) until transfer to dry ice for
shipment to Cetero Research (Toronto, ON, Canada, for
DAG and Houston, TX, USA, for DCA and adipokines).
© 2015 Wiley Periodicals, Inc.
ATX-101 and lipid pharmacodynamics . P. Walker & D. Lee
DCA and DAG plasma samples were analyzed under a
validated method using high-performance liquid chro-
matography with tandem mass spectrometry performed
by Cetero Research (Houston and Toronto, respec-
tively). Determination of lipid (total cholesterol, FFA
and total triglycerides) and adipokine (e.g., CRP and
apolipoprotein B) concentrations was performed by
Cetero Research (Fargo, ND, USA).
Safety assessments
Vital signs and weight were assessed on the screening
day, at each stage, and at post-ATX-101 dosing days
3, 7, 14, 21, and 28. Physical examination, 12-lead
electrocardiograms, and standard clinical laboratory
tests were undertaken at screening and at the end of
the study. For women of childbearing potential, preg-
nancy tests were performed at screening, before ATX-
101 administration, and at day 28.
The use of concomitant medications and the occur-
rence of adverse events (AEs) were monitored on each
assessment day of both stages, including at each fol-
low-up visit to the end of the study. Other safety
assessments could be made at the investigator’s discre-
tion. Treatment area or local reactions, such as edema,
bruising, erythema, dyspigmentation, induration,
numbness, pain, paresthesia, and pruritus, were
recorded as AEs. The relationship to treatment was
determined by the investigator, and the severity of all
AEs was graded as mild, moderate, or severe. Serious
AEs included any event that constituted a significant
medical hazard or side effect, regardless of its relation-
ship to ATX-101 treatment.
Statistical methods
The total sample size of up to 10 subjects was based
on clinical rather than statistical considerations and
was considered sufficient to provide safety, serum lipid,
and PK/PD-related data to achieve the objectives of
this study.
PK and PD analyses were performed using standard
noncompartmental techniques. The analytical data
were used to calculate PK parameters. PK measure-
ments included area under the plasma concentration–
time curve from time 0–24 h postdose (AUC0-24) and
time 0 to 12 h postdose (AUC0-12; under fasting condi-
tions), maximum observed plasma concentration
(Cmax), and median time to reach Cmax (tmax). Postdose
DCA concentrations were not adjusted for baseline, but
were reported as total DCA exposure (endoge-
nous + injected DCA). PD calculations included
35
ATX-101 and lipid pharmacodynamics . P. Walker & D. Lee

maximum observed concentration (ECmax), minimum were highly variable. Mean AUC0-24 and Cmax were
observed concentration (ECmin), area under the plasma 3479  2238 ng•h/mL and 249  161 ng/mL, respec-
concentration–time curve from time 0–24 h postdose tively. Median tmax was 15.5 (range, 0.5–24.5 h).
(AUEC0-24), area under the plasma concentration–time Administration of ATX-101 resulted in an approximate
curve from time 0–12 h postdose (AUEC0-12; under twofold increase in mean AUC0-24 and a 3.6-fold increase
fasting conditions), time to reach ECmax (ETmax), and in Cmax compared with endogenous DCA levels. Following
time to reach ECmin (ETmin). For PK parameters (DCA) ATX-101 injection, mean DCA values for AUC0-24 and
and PD parameters (lipids and adipokines), except for Cmax were 7241  2092 ng•h/mL and 902  153 ng/
insulin, baseline was set as the mean of all predose mL, respectively. The median tmax was 0.75 (0.25–
24-h plasma levels. Because of instability, the baseline 1.50) h. For some subjects in the population, the post-
level for insulin was a point-by-point 24-h profile. ATX-101 DCA levels were lower than endogenous base-
line DCA levels of other subjects in the population. On
average, DCA plasma concentrations returned to endog-
Results
enous levels by 12 h post-ATX-101 administration.
Subject disposition and demographics
Serum lipid pharmacodynamics
Ten subjects (five males and five females) completed
the study. The mean age was 22.9  4.3 years, and Pharmacodynamics of total cholesterol, triglycerides,
the majority of subjects (80.0%) were White. Of the FFA, 1,2_DAG, and 1,3_DAG are shown in Table 1. No
remaining subjects, one was classified as American clinically meaningful differences were found in lipid PD
Indian or Alaskan Native, and one was Black. The pre- vs. post-ATX-101 administration for total choles-
mean BMI for all subjects was 24.6  3.0 kg/m2. terol, total triglycerides, or FFA plasma levels (Fig. 1b–d).

Deoxycholic acid pharmacokinetics Adipokine concentrations

Mean baseline DCA plasma concentrations over time are Mean CRP plasma concentrations for pre- and post-
shown in Figure 1a. Endogenous concentrations of DCA ATX-101 injection were 0.12  0.22 mg/dL and

(a) DCA (b) Total Cholesterol

1200
Pre-ATX-101 250
Pre-ATX-101
Post-ATX-101
Post-ATX-101
1000
Mean total cholesterol plasma
concentration (mg/dL)
concentration (ng/mL)

225
Mean DCA plasma

800

600 200

400
175
200

0 150 Normal range 100 - 200 mg/dL

0 2 4 6 8 10 12 14 16 18 20 22 24 26 0 2 4 6 8 10 12 14 16 18 20 22 24 26
Time (Hours) Time (Hours)
(c) Total Triglycerides (d) Total FFA
250 1.0
Pre-ATX-101 Pre-ATX-101
Post-ATX-101 Post-ATX-101
Mean total triglycerides plasma

0.8
Mean total FFA plasma
concentration (mg/dL)

concentration (meq/L)

200

0.6
150
0.4

100
0.2

50 Normal range 50 - 200 mg/dL 0.0 Normal range 0.1 - 0.6 meq/L
0 2 4 6 8 10 12 14 16 18 20 22 24 26 0 2 4 6 8 10 12 14 16 18 20 22 24 26
Time (Hours) Time (Hours)

Figure 1 Mean (SD) plasma concentrations for endogenous levels and post-ATX-101 administration levels for DCA (a), total choles-
terol (b), total triglycerides (c), and total FFA (d). DCA, deoxycholic acid; FFA, free fatty acids; SD, standard deviation.

36 © 2015 Wiley Periodicals, Inc.

 ATX-101 and lipid pharmacodynamics . P. Walker & D. Lee

Table 1 Pharmacodynamics of total cholesterol, triglycerides, free fatty acids, 1,2 diacylglycerol, and 1,3 diacylglycerol (mean, SD)

AUEC0-24* ECmax† ETmax (h)

Mean (SD) Mean (SD) Median (range)

Pre-ATX-101 Post-ATX-101 Pre-ATX-101 Post-ATX-101 Pre-ATX-101 Post-ATX-101

Total cholesterol 4414 (683) 4157 (567) 193 (30) 184 (26) 15.5 (6.0–24.5) 20.0 (0.0–24.5)
Total triglycerides 2348 (880) 2465 (1037) 136 (55) 153 (61) 15.5 (15.5–24.5) 15.5 (15.5–24.5)
Free fatty acids 10.1 (2.6) 9.47 (2.17) 0.74 (0.20) 0.86 (0.27) 12.0 (0.0–24.5) 12.0 (0.0–12.0)
1,2 diacylglycerol 44.1 (16.4) 45.0 (15.2) 2.3 (0.70) 2.5 (0.85) 15.5 (6.0–24.5) 15.5 (0.0–24.5)
1,3 diacylglycerol 2.4 (2.30) 1.8 (1.94) 0.14 (0.11) 0.12 (0.12) 13.8 (0.0–24.5) 0.5 (0.0–24.5)

AUEC0-24, area under the concentration–time curve from time 0 (predose) to 24 h; ECmax, maximum observed concentration; ETmax,
time to maximum observed concentration; SD, standard deviation.
*
mg
h/dL for total cholesterol and total triglycerides; meq
h/L for free fatty acids; lg
h/mL for diacylglycerol.
†
mg/dL for total cholesterol and triglycerides; meq/L for free fatty acids; lg/mL for diacylglycerol.

0.54  0.81 mg/dL, respectively. Mean IL-6 plasma

concentrations for pre- and post-ATX-101 injection
were 0.11  0.36 pg/dL and 1.86  1.90 pg/dL,
respectively. No clinically significant changes were
detected in Cmax from pre- to postdose for IL-15 (1.24
 0.16 pg/mL to 1.48  0.20 pg/mL), TNF-a (6.93
 1.25 pg/mL to 9.93  3.00 pg/mL), apolipoprotein
B (85.4  16.0 mg/dL to 90.3  14.2 mg/dL), adipo-
nectin (3116  1746 ng/mL to 4031  2601 ng/mL),
insulin (694  714 pg/mL to 783  692 pg/mL), leptin
(8800  8887 pg/mL to 18081  18371 pg/mL), and
resistin (5806  1129 pg/mL to 7351  1633 pg/mL).
PD parameters could not be calculated for IL-1a, IL-1b,
or IFN-c.
Safety assessments
Ten subjects experienced a total of 41 AEs during stage
B. No death, serious, or systemic AE was observed. No
subject discontinued the study for any reason.
The majority of treatment-emergent AEs were associ-
ated with the area treated and were transient and mild
in severity. Reported AEs (Medical Dictionary for Regula-
tory Activities [MedDRA] preferred terms) included the
following: injection site pain (12 events); injection site
erythema (8); injection site edema (3); injection site
hematoma (10); injection site numbness (2); and one
event each of injection site warmth, injection site reac-
tion, hyperhidrosis, pallor, and tremor. One event of
muscle tightness was considered not related to ATX-
101 administration.
No AEs related to clinical laboratory values were
reported. No clinically significant changes in laboratory
values, vital sign data, or electrocardiograms were
observed during the study.
Discussion
Observations from this open-label phase 1 study indi-
cate that injection of ATX-101 into abdominal subcu-
taneous fat (1) does not cause increases in plasma
concentrations of DCA outside the normal range of
variability for endogenous DCA, (2) does not cause
clinically meaningful increases in systemic concentra-
tions of lipids or adipokines, and (3) is safe and well
tolerated.
The PK profile of circulating DCA following injection
of 100 mg ATX-101 indicates that DCA was rapidly
absorbed from the injection sites into the plasma,
peaked at a plasma concentration 3.6-fold greater than
average endogenous DCA plasma concentrations and
returned to baseline by 12 h postdose. The increased
average exposure from exogenous DCA experienced by
subjects in this study was transient and consistent with
previous studies in which ATX-101 was injected into
SMF.13–16 Furthermore, as the assay does not distinguish
between the DCA in ATX-101 and endogenous DCA,
postdose concentrations were not adjusted for baseline;
we report total exposure of DCA, endogenous plus
injected, to demonstrate the total exposure to endoge-
nous DCA and injected ATX-101.
Overall, cholesterol, total triglycerides, and FFA lev-
els were similar after a meal/snack to those observed
after ATX-101 administration, suggesting little contri-
bution of treatment to physiological cholesterol, total
triglycerides, or FFA levels. Together, these findings on
circulating lipids suggest that ATX-101 did not demon-
strate clinically important effects on lipid profiles.
Mean concentrations of both CRP and IL-6 were
within normal ranges post-ATX-101 dosing. No clini-
cally significant changes were observed in ECmax or

© 2015 Wiley Periodicals, Inc. 37

ATX-101 and lipid pharmacodynamics . P. Walker & D. Lee
ECmin for IL-15, TNF-a, apolipoprotein B, adiponectin,
insulin, leptin, and resistin. The data indicate that
ATX-101 had no important effects on circulating
adipokines, which are released from white adipose tis-
sue and may be important in diverse metabolic func-
tions related to energy balance and inflammatory
processes.17,18
The most common AEs associated with the treat-
ment area were transient, mild in severity, and
resolved within 28 days of treatment. No discontinua-
tion, death, or serious AE occurred. No clinically signif-
icant change from baseline in laboratory values or
vital signs was observed. Several phase 2 and phase 3
randomized placebo-controlled clinical trials of ATX-
101 for the reduction of SMF have been completed to
establish the safety and efficacy of ATX-101 in support
of the FDA New Drug Application. The PK and AE
results are consistent with other studies with ATX-
101.19–22
Potential limitations of this PK, PD, and safety analy-
sis of ATX-101 include the small sample size, the
open-label design, and the inclusion in the study of
only healthy individuals with normal lipid profiles.
Planned and completed clinical trials include larger
sample sizes, a range of efficacy endpoints, randomized,
placebo-controlled study designs, and inclusion of a
more diverse patient population.
These data support the safety and tolerability of
ATX-101 and its predictable PK profile. ATX-101
injections were not associated with any systemic
effects. Plasma concentrations of lipids, DCA, and
adipokines did not fall outside the normal range of
endogenous fasting or postprandial concentrations and
were therefore not considered clinically meaningful.
AEs associated with ATX-101 usually showed a tempo-
ral relationship to dosing and were transient and mild
in severity. Together with evidence from previous con-
trolled trials, data from this study support continued
evaluation of ATX-101, a proprietary formulation of
synthetic DCA as a potential first-in-class adipocytolytic
drug for contouring the submental area through the
reduction of SMF.
Acknowledgments
Funding for editorial support was provided by Kythera
Biopharmaceuticals, Inc., Calabasas, CA, USA. Writing
and editorial assistance was provided by Paula G.
Davis, PhD, and Antoinette Campo of SCI Scientific
Communications & Information, Parsippany, NJ, USA,
and Beth Martin of Scientific Commercialization, Los
Angeles, CA, USA.
38
References
1 Hatef DA, Koshy JC, Sandoval SE et al. The submental fat
compartment of the neck. Semin Plast Surg 2009; 23:
288–91.
2 Patel BC. Aesthetic surgery of the aging neck: options
and techniques. Orbit 2006; 25: 327–56.
3 Rohrich RJ, Rios JL, Smith PD et al. Neck rejuvenation
revisited. Plast Reconstr Surg 2006; 118: 1251–63.
4 Schlessinger J, Weiss SR, Jewell M et al. Perceptions and
practices in submental fat treatment: a survey of physi-
cians and patients. Skinmed 2013; 11: 27–31.
5 Huettner F, Vasconez LO, de la Torre JI. Neck rejuvena-
tion–anatomy and clinical correlation. Facial Plast Surg
2012; 28: 40–51.
6 Dayan SH, Arkins JP, Chaudhry R. Minimally invasive
neck lifts: have they replaced neck lift surgery? Facial
Plast Surg Clin North Am 2013; 21: 265–70.
7 Gonzalez F. Nuclear receptor control of enterohepatic cir-
culation. Compr Physiol 2012; 2: 2811–28.
8 Kevresan S, Kuhajda K, Kandrac J et al. Biosynthesis of
bile acids in mammalian liver. Eur J Drug Metab Pharma-
cokinet 2006; 31: 145–56.
9 Rotunda AM. Injectable treatments for adipose tissue: ter-
minology, mechanism, and tissue interaction. Lasers Surg
Med 2009; 41: 714–20.
10 Rotunda AM, Suzuki H, Moy RL et al. Detergent effects of
sodium deoxycholate are a major feature of an injectable
phosphatidylcholine formulation used for localized fat dis-
solution. Dermatol Surg 2004; 30: 1001–8.
11 Thuangtong R, Bentow JJ, Knopp K et al. Tissue-selective
effects of injected deoxycholate. Dermatol Surg 2010; 36:
899–908.
12 Yagima Odo ME, Cuce LC, Odo LM et al. Action of sodium
deoxycholate on subcutaneous human tissue: local and
systemic effects. Dermatol Surg 2007; 33: 177–88.
13 Setchell KD, Lawson AM, Blackstock EJ et al. Diurnal
changes in serum unconjugated bile acids in normal
man. Gut 1982; 23: 637–42.
14 Tagliacozzi D, Mozzi AF, Casetta B et al. Quantitative
analysis of bile acids in human plasma by liquid chroma-
tography-electrospray tandem mass spectrometry: a sim-
ple and rapid one-step method. Clin Chem Lab Med 2003;
41: 1633–41.
15 Takikawa H, Otsuka H, Beppu T et al. Quantitative deter-
mination of bile acid glucuronides in serum by mass frag-
mentography. J Biochem 1982; 92: 985–98.
16 Walker P, Lee D. Open-label pharmacokinetic study to
evaluate lipid levels in the blood following injections of
ATX-101 (synthetically derived sodium deoxycholate).
J Am Acad Dermatol 2013; 68(Suppl. 1): AB1.
17 Trayhurn P, Bing C, Wood IS. Adipose tissue and adipo-
kines–energy regulation from the human perspective.
J Nutr 2006; 136(7 Suppl): 1935S–9S.
18 Lau DC, Dhillon B, Yan H et al. Adipokines: molecular
links between obesity and atheroslcerosis. Am J Physiol
Heart Circ Physiol 2005; 288: H2031–41.
© 2015 Wiley Periodicals, Inc.

19 Dover J, Schlessinger J, Young L. Reduction of submental
fat with ATX-101: results from a phase IIB study using
investigator, subject, and magnetic resonance imaging
assessments. J Am Acad Dermatol 2012; 66(Suppl. 1):
AB29.
20 Goodman G, Lee D, Smith KJ. Reduction of submental fat
with ATX-101: a pooled analysis of two international
multicenter, double-blind, randomized, placebo-controlled
studies. J Am Acad Dermatol 2012; 66(Suppl. 1): AB11.
© 2015 Wiley Periodicals, Inc.
ATX-101 and lipid pharmacodynamics . P. Walker & D. Lee
21 Rzany B, Griffiths T, Walker P et al. Reduction of
unwanted submental fat with ATX-101 (deoxycholic
acid), an adipocytolytic injectable treatment: results from
a phase III, randomized, placebo-controlled study. Br J
Dermatol 2014; 170: 445–53.
22 Smith K, Goodman G, Walker P. ATX-101 treatment
offers long-term durability of submental fat reduction:
preliminary follow-up study results of subjects from phase
II studies. J Am Acad Dermatol 2012; 66(Suppl. 1): AB23.
39
Copyright of Journal of Cosmetic Dermatology is the property of Wiley-Blackwell and its
content may not be copied or emailed to multiple sites or posted to a listserv without the
copyright holder's express written permission. However, users may print, download, or email
articles for individual use.