2015 10 VOL .04

Belviq tab. 10mg(Lorcaserin) 10MG Selective 5-HT2C Receptor Agonist

/

(, : HH911G) () ()

(2015.10.05-13) 2015

, , , , , ,

134-090 892 [TEL] 02.440.6977 / 02.440.6992() [FAX] 02.440.6984

15.10.30 / http://pharm.khnmc.or.kr

[/]Belviq tab. 10mg (Lorcaserin HCl) 10MG

1.

()

2.

lorcaserin 10mg

3.

4.

5-HT2C Receptor , (arcuate

nucleus) pro-opiomelanocortin (POMC)

melanocortin-4 -melanocortin

,

lorcaserin

2C

5.

BMI 30kg/m2 , BMI

27kg/m2

6.

: 1 10mg, 1 2

12 5%

1) :

2) :

3) :

1) ~ :

2) :

:

7.

Peak : 1.5-2hr

: 11hr

70%

: SULTs, UGTs, multiple CYP

: urine(92.3%), feces(2.2%)

1 2015 10

8.

: (15-17%)

: ( 29%; : 2%)

: (12%)

: (6-12%)

: (14%), nasopharyngitis(11-13%)

9.

(SNRIs/SSRIs, MAO ,

TCAs, St John's wort, cabergoline, dextromethorphan,

linezolid, lithium, tramadol ) .

CYP 2D6

.

10.

, ,

11.

: FDA X

: ,

12.

, (1~30)

, .

, ,

.

12 .

lorcaserin HCl Orlistat

10mg 120mg

100T / Bottle 84C / Box

(: A, 10)

(: ROCHE, XENICAL120)

/ Arena Pharmaceuticals GmBH / /

5-HT2C

( )

lipase

(BMI) 30kg/m2 (.

, , 2 ) 27kg/m2

(BMI) 30kg/m2 (,

, , ) 27kg/m2

/ 1 10mg,

1 2

1 120mg,

1 3 1

PK

Peak : 1.5-2

70%

: 11

: SULTs, UGTs, multiple CYP

: urine(92.3%), feces(2.2%)

Peak : 6-8

99%

: 16

:

: urine(2%), feces (97%)

, , , , , , ,

, , ,

, , , /,

, ,

1)

2)

3)

4)

1)

2)

3)

FDA X FDA X

2 2015 10

Reference

1. : http://www.kimsonline.co.kr

2. : http://www.health.kr

3. MICROMEDEX 2.0

4.

: ()

1.

. ,

3~6 10% .

1) : (BMI) 30kg/m2 , 27kg/m2 (, , )

( )

2) : (BMI) 25kg/m2 , 23kg/m2

(- )

2.

1)

.

.

2) 5~10%

.

3) .

3 5~10%

.

4) , .

.

5) , ,

. ,

.

6)

.

3.

Ref) Adapted from G. W. Kim et al: Antiobesity pharmacotherapy: new drugs and emerging targets. Clin Pharmacol Ther. 2014;95:5366 (25),

with permission. American Society for Clinical Pharmacology and Therapeutics.

3 2015 10

Special Issue

AGRP, Agouti-related peptide

CART, Cocaine amphetamine-related

transcript

CCK1R, CCK1 receptor

GLP1R, GLP-1 receptor

CTR, calcitonin receptor

D1, dopamine 1 receptor

D2, dopamine 2 receptor

DAT, dopamine active transporter

DVC, dorsal vagal complex

GHSR, GH secretagogue receptor

LepR, leptin receptor

MC3/4R, melanocortin receptor type

MCH1R, melanin-concentrating hormone

1 receptor

NPY, neuropeptide Y

PVN, paraventricular nucleus

Y1/Y5R, Y1/Y5 receptor

Y2R, Y2 receptor

Y4R, Y4 receptor

MSH, melanocyte-stimulating hormone

-OR, -opioid receptor

4.

1)

* Weight Loss Above Diet and Lifestyle Alone, Mean Weight Loss, % or kga ; Duration of Clinical Studies

a Mean weight loss in excess of placebo as percentage of initial body weight or mean kilogram weight loss over placebo

4 2015 10

()

Locaserin

(Belviq)

Orlistat

(Xenical) Phentermine Diethylpropion Phendimetrazine Mazindol

Selective serotonin 5-HT2C

agonist :

Pancreatic and gastric

lipase inhibitor :

Pancreatic Lipase

Norepinephrine-releasing agent : Norepinephrine dopamine

/

1 10mg, 1 2

,

3

1 3 120mg ,

,

3

1 1-2 ,

1 18.75mg

37.5mg ,

.

(30mg) 1 1,

(3)

1 3 1

1 2

5mg

(1 75mg),

(3)

1 2 3

1 .

1 17.5mg

35mg, 70mg

,

(3)

1 1mg 3 1

1 1 1~2mg

1

1 1 1mg

,

(3)

, , ,

, ,

, ,

,

,

, , , , , , ,

/,

:

SSRI, SNRI/MAOI, St

Johns wort, triptans,

buproprion,

dextromethorphan

,

, / MAOI(Monoamine Oxidase Inhibitor) , , , ,

, , ,

Efficacy* 3.6 kg; 1 y 2.9 3.4 kg; 1 y 3.6 kg; 224 wk 3.0 kg; 652 wk 3.4 kg; 12 wk 3.12 kg; 12 wk

FDA

In 2012

for chronic weight

management

In 1999

for chronic weight

management

In 1960s

for short-term use

(3 mo)

In 1960s

for short term Use

(3 mo)

In 1960s

for short-term use

(3 mo)

Marketing discontinued

in USA

2) FDA ( )

* Weight Loss Above Diet and Lifestyle Alone, Mean Weight Loss, % or kg a ; Duration of Clinical Studies

a Mean weight loss in excess of placebo as percentage of initial body weight or mean kilogram weight loss over placebo

3)

5 2015 10

()

Phentermine(P)/ topiramate(T)

(Qsymia)

Naltrexone/ bupropion

(Contrave)

Liraglutide

(Saxenda)

GABA receptor modulation(T)

plus norepinephrinereleasing

agent (P)

Reuptake inhibitor of dopamine

and norepinephrine(bupropion)

and opioid antagonist

(naltrexone)

GLP-1 agonist

/

3.75 mg P/23 mg T ER QD

(starting dose)

7.5 mg P/46 mg T ER daily

(recommended dose)

15 mg P/92 mg P/T ER daily

(high dose)

32mg/360mg 2 tablets QID

(high dose) 3.0mg injectable

Insomnia, dry mouth,

constipation, paraesthesia,

dizziness, dysgeusia

Nausea, constipation, headache,

vomiting, dizziness Nausea, vomiting, pancreatitis

Pregnancy and breastfeeding,

hyperthyroidism, glaucoma,

MAO inhibitor,

sympathomimetic amines

Uncontrolled hypertension,

seizure disorders,

anorexia nervosa or bulimia,

drug or alcohol withdrawal,

MAO inhibitors

Medullary thyroid cancer history,

multiple endocrine neoplasia

type 2 history

Efficacy*

6.6 kg (recommended dose),

6.6% 8.6 kg (high dose),

8.6%; 1 y

4.8%; 1y 5.8 kg; 1 y

FDA

FDA approved in 2012

for chronic weight management

FDA approved in 2014

for chronic weight management

FDA approved in 2014

for chronic weight management

Mechanism of action Status Comments

Exenatide GLP-1 analogue Phase III

Injectable formulation; currently

approved for the treatment

of type 2 diabetes

Cetilistat Gastrointestinal and pancreatic

lipase inhibitor Phase III completed

Orally active; recently approved

in Japan for the treatment of obesity

with complications

Velneperit Neuropeptide Y5 receptor inhibitor,

appetite suppression Phase II Orally active

Tesofensine Inhibition of serotonin, dopamine,

and noradrenaline reuptake Phase III

Orally active; originally investigated

for the treatment of Alzheimer's

disease and Parkinson's disease.

6 2015 10

Mechanism of action Status Comments

Metreleptin Leptin receptor agonist Phase III

Injectable formulation; FDA approved

orphan drug indicated as

an adjunct to diet as replacement

therapy for treating the complications

of leptin deficiency in patients with

congenital or acquired

generalized lipodystrophy.

Bupropion SR

+

zonisamide SR

(Empatic)

Dopamine and norepinephrine

reuptake inhibitor +

antiepileptic causing enhancement

of dopamine and serotonin

neurotransmission

Phase II completed Orally active

Obinepitide Dual neuropeptide Y2/Y4 receptor

agonist Phase II Injectable formulation

Reference

1. Apovian et al. Guidelines on Pharmacological Management of Obesity. J Clin Endocrinol Metab, February 2015, 100(2):342362

2. Kakkar AK1, Dahiya N2. Drug treatment of obesity: current status and future prospects. Eur J Intern Med. 2015 Mar;26(2):89-94.

3. Pucci and Finer. New Medications for Treatment of Obesity: Metabolic and Cardiovascular Effects. Canadian Journal of Cardiology

31 (2015) 142-152

4. http://www.micromedexsolutions.com/

5. http://www.fda.gov/Drugs/default.htm

6. 2012,

: ()

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.

CaSO4 ephedrine

.

*

ephedrine-caffein

ephedrine -adrenergic

.

7.

: 1 1 2~5

(7~14): 1 1/2~1 1 2~5

7 2015 10

8.

1) 1 3g( 19.5mg) ,

1 1 .

(* PDR(Physicians Desk Reference) 1

total alkaloid(ephedrine) 15-30mg, 1

120mg/day .)

2) Ephedrine ,

, , .

3) , ,

.

4)

: Furazolidone, , , .

: Monoamine oxidase inhibitor,

Adrenal cortical hormone(), Isoniazid, adrenergic

2-receptor stimulants(Fenoterol, Clenbuterol, Salbutamol,

Terbutaline, Isoproterenol).

9.

3. (1~30)

Reference

1. . . . 1995.

2. . Zucher Rats , , , . .

2005

3. , . - , , . .

2007

4. . . . 2007

5. , . . 41 . . 2011 6. . . . 2006 7. . . .(1998), 15 3.

: ()

,

, .

.

, (, ), ,

.

.

Ephedrine

Pseudoephedrine

1.

2. :

,

3. ():

, ,

,

4.

5.

CaSO4.2H20 1.

2. ,

Atractylon

Hinesol

1.

2.

3.

4. :

5.

6.

Caffein

Polyphenol(catechin) , , , ,

8 2015 10

2015

2015 .

* 2015.10.30 SKY CellFLU PFS 0.5mL

3

[]SKY CellFLU PFS 0.25mL (Cell culture inactivated influenza virus antigen)

0.25ML(SK)

6~35

[]Vaxigrip inj. 0.25mL (Purified inactivated influenza virus antigen)

0.25ML ()

[]SKY CellFLU PFS 0.5mL (Cell culture inactivated influenza virus antigen)

0.5ML(SK)

36

[]Vaxigrip inj. 0.5mL (Purified inactivated influenza virus antigen)

0.5ML ()

[]FluAD inj.Adjuvanted vaccine 0.5ml(Purified inactivated influenza virus antigen)

0.5ML () 65

4 []FluaRIX TETRA PFS 0.5ml (GSK) 36

(2015.10.05-13)

() 2015 10 5 13 .

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10 5 ,

. 4000 .