WOLFGANG A. RITSCHEL
`
`GREGORY L. KEARNS
`
`HANDBOOK 0f
`
`BASIC PHARMACOKINETICS
`
`
`
`...INCLUDING CLINICAL APPLICATIONS
`
`SIXTH EDITION
`
`AQUESTIVE EXHIBIT 1077 Page 0001
`. QUESTIVE EXHIBIT 1077 Page 0001
`
`

`

`Handbook
`
`of
`
`Basic
`
`Pharmacokinetics
`
`.
`
`.
`
`. including Clinical Applications
`
`Sixth Edition
`
`Wolfgang A. Ritschel
`Ph.D., M.D., Mr. Pharm., F.A.S.A., F.C.P.
`
`Professor Emeritus of Pharmacokinetics
`and Biopharmaceutics
`College of Pharmacy
`Professor of Pharmacology
`and Cell Biophysics
`College of Medicine
`University of Cincinnati
`Cincinnati, Ohio
`
`Gregory L. Kearns
`
`Pharm.D., Ph.D., F.C.P..
`
`Marion Merrell Dow/Missouri Chair in Pediatric Pharmacology
`Professor of Pediatrics and Pharmacology
`University of Missouri—Kansas City
`Chief, Division ofPediatric Pharmacology and Medical Tom'colOgY
`DireCtOI', Pediatric Pharmacology Research Unit
`Children’s Mercy Hospitals and Clinics
`Kansas City, Missouri
`
`a
`
`AMERICANP
`
`[m
`
`,
`
`—
`. ILA-r
`L.
`:
`APhA
`CISTS ASSOCIATION
`WASHINGTON, DC.
`
`..
`hall not be deemed,
`:1:imamor trademark.
`m may exerdse the same
`mer.
`ifilifiiifixfgiiiii
`5 not been included does
`Further, no official sup-
`y is intended or inferred.
`:arch and clinical experi-
`1gtherapymustbebased
`.pletenessoftheinforma-
`onsible for the continued
`is information. Therefore,
`:0 claims, loss, or damage
`herein.
`
`reflected in the literature
`
`.
`
`i
`
`A QUESTIVE EXHIBIT 1077 Page 0002
`
`AQUESTIVE EXHIBIT 1077 Page 0002
`
`

`

`
`
`
`Acquiring Editor: Julian I. Graubart
`Managing Editor: L. Luan Corrigan
`Typography: Circle Graphics
`Indexing: Lillian Rodberg
`
`©2004 by the American Pharmacists Association
`Published by the American Pharmacists Association, 2215 Constitution Avenue, NW, Washington, DC 20037—2985
`APhA was founded in 1852 as the American Pharmaceutical Association.
`All rights reserved.
`
`No part of this book may be reproduced, stored in a retrieval system, or transmitted in anyform or by any means, electronic,
`mechanical, photocopying, recording, or otherwise, without written permission from thepublisher.
`
`To comment on this book via e-mail, send your message to the publisher at aphab00k5@aphanet.org.
`Library of Congress Cataloging-in—Publication Data
`
`Ritschel, W. A. (Wolfgang A.)
`Handbook ofbasic pharmacokinetics— including clinical applications /
`Wolfgang A. Ritschel, Gregory L. Kearns.— 6th ed.
`p. ; cm.
`Includes bibliographical references and index.
`ISBN 1-58212-054-4
`l. Pharmacokinetics—Handbooks, manuals, etc. 2. Clinical
`pharmacology—Handbooks, manuals, etc.
`[DNLM: I. Pharmacokinetics—Handbooks. QV 39 R612h 2004] I. Kearns,
`Gregory L. 11. American Pharmaceutical Association. III. Title.
`
`RM301.5.R57 2004
`615.7—dc22
`
`2003026662
`
`
`How to Order This Book
`
`Online: www.pharmacist.com
`
`By phone: 800-878-0729 (from the United States and Canada)
`
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`
`
`
`AQUESTIVE EXHIBIT 1077 Page 0003
`AQUESTIVE EXHIBIT 1077 Page 0003
`
`

`

`Appendix
`Pharmacokinetic Parameters of
`Important Drugs
`
`Pharmacokinetic data have become an integral part ofthe pharmacologic characterization
`of a drug. Regulatory agencies require determination of pharmacokinetic data in Phase I
`studies and submission of pharmacokinetic drug data as part of a New Drug Application.
`For research and development, pharmacokinetic drug data are used in design of new
`chemical entities based on structure-activity relationships, and for design ofproper dosage
`forms to result in the desired therapeutic concentrations.
`Clinically, pharmacokinetic data are used for the design of dosage regimens in drug-
`naive patients, for drug monitoring, and for dosage regimen adjustment. Furthermore,
`pharmacokinetic data give information or indications whether a drug may be excreted in
`milk (pKa), whether the half—life may change in renal impairment or advanced age (F51),
`and whether protein binding may be ofclinical importance regarding displacement, hypo-
`and hyper-albuminemia (if EPB > 80 percent), etc.
`Data listed in the appendix have been compiled and extracted from more than a thou—
`sand publications. Hence, it is not possible for reasons of space to give a listing of refer—
`ences. The data have been listed as mean data. Reports are often conflicting, contradictory,
`or at least show Wide variations among investigators. This, in part, is due to different ana-
`lytical methods employed for drug assay, different population groups, and different exper—
`imental conditions.
`
`Only the elimination half—life ranges are listed for many drugs. This should be indica—
`tive that a calculated dosage regimen based on literature mean data may not result in a
`desired therapeutic concentration and hence, drug monitoring becomes more important.
`Also, most of the pharmacokinetic data refer to healthy, young adults. However, many
`physiologic and pathologic conditions may greatly influence the pharmacokinetics of a
`drug. Again, drug monitoring in such situations may become important.
`The following symbols are used:
`
`tm
`kel or B
`Vd
`
`= elimination (terminal) half—life
`= terminal disposition rate constant
`= apparent volume of distribution (Vdfi or Vd am)
`
`367
`
`‘ QUESTIVE EXHIBIT 1077 Page 0004
`
`AQUESTIVE EXHIBIT 1077 Page 0004
`
`

`

`
`
`368 APPENDIX
`
`tmax “.1
`
`D1'
`
`
`
`fun-n"[LI
`
`”all
`
`orMEC run/Mn
`
`I‘ll
`
`EPB [0/'l
`
`nIlmi
`
`fh—fl
`
`kel0"BVa
`
`tI/l [h]
`
`mam:
`
`ParametersofImportantDrugs Ther.Range
`
`Fe]
`
`= fraction of unchanged drug excreted in urine
`= fraction of drug absorbed = absolute bioavailability. Unless other-
`wise indicated, f refers to peroral administration.
`= extent of protein binding in plasma
`Ther. Range or MEC = therapeutic range or minimum effective concentration
`Note: For antimicrobial agents the MEC or MIC (minimum inhib-
`itory concentration) depends on the sensitivity of the micro-
`organism. Hence, a sensitivity test may be more appropriate than
`a listed mean value.
`
`f E
`
`PB
`
`= usual route of administration. This listing is not exhaustive. Even
`if not listed, the drug may be used by other routes.
`= dose size usually employed as maintenance dose. Loading doses are
`not listed.
`
`= dosing interval for multiple closing
`2 time to reach the peak upon extravascular administration
`= Not applicable
`= Data not available
`
`= Vd/f
`= Cmax or C53...x
`= Cmin 01' Cirsiin
`
`= if required, repeat dose after 2 h
`= umol/L
`= poor metabolizer
`= effective concentration 50% = ECSO
`
`URA
`
`m w
`
`,
`
`5Fcnacokinetic
`
`AQUESTIVE EXHIBIT 1077 Page 0005
`AQUESTIVE EXHIBIT 1077 Page 00
`A
`
`

`

` Pharmacokinetic Parameters of Important Drugs (Continued)
`
`DRUG
`Clinafloxacin
`.
`.
`c|1ndamycm
`c1odronate
`
`
`
`
`
`
`
`
`
`
`
`
`0'0“
`0-017
`0.086
`0.086
`0.0147
`1.155
`0.0125
`0-73
`0.21
`0.02
`0.231
`0.231
`0.8662
`
`0‘12
`1‘54”
`35
`—
`1.1
`0.35
`3.5 (2 5)
`2 1
`_
`'
`345
`-
`67
`-
`0.5
`0.55
`~
`1 7
`
`0'15
`2
`0'0
`0.3
`0
`__
`0.4
`07
`_
`'
`01
`'
`0 15
`‘
`0.75
`0.3
`0
`
`1
`(175
`08
`1
`0'5
`1
`0.5
`1
`—
`05
`0.44
`1 I.M.
`11.M.
`1104
`
`_
`
`95
`47.82
`20
`98
`_
`94
`90
`40
`10—25
`40
`20
`0
`2
`35
`
`.
`A. 2.95
`a:1.5
`B:8.3
`—
`_
`A' 2 9
`-
`-
`__
`. 8 5
`B-
`-
`_ 8 1
`a.
`-
`13:21.},
`1
`.
`—
`_
`NA
`
`90
`P0
`P0
`Po
`P0
`P0
`00
`POI'V
`P0.IM.SC
`P0.IV
`PO'IVJM
`1101,90
`POJV
`
`500
`1'2
`0.15—0.3
`75
`15—60
`500
`125—450
`5‘30
`30
`05 1
`~ -
`2.5—5mg/kg
`1.5 rug/kg
`1v10—25
`po 30
`
`4‘5
`8—12
`H
`4
`2
`24
`6
`24
`'
`H
`smgle
`24
`6.12
`‘2
`3
`12
`
`4
`2
`3
`1
`_
`1
`3.4
`1
`1.25
`1 (05—2)
`2
`2.
`01
`._
`‘
`
`
`Thar. Range
`D
`1.
`3:].
`ukA
`EP8
`or ME.C
`[mg]
`[11]
`9'“
`1%]
`f
`r.
`[llvkd 1
`w"B
`"R
`[WM]
`12
`1 5(1 3)
`0
`-
`9
`111-11
`_
`.
`"“
`035
`_
`12.,
`6
`1
`200—40
`p0
`#‘fl—f—f—g
`0.124
`1.9
`0-
`150-450
`PO
`5.6
`1
`01
`03
`90
`B:7.72
`00822;“5
`24
`4&6
`100
`vAGovula
`2.8 12—3)
`0 3
`—
`'
`100
`2“
`G em
`0243
`1
`'
`—
`11
`004
`_
`0'02“
`2
`05-1
`VA cr
`_
`_
`"
`0-052
`14
`—
`—
`‘
`__
`0.8,,
`.50
`400-1600
`1
`0.048
`27
`0.026
`98.93
`<003
`‘
`(2 x 400 mg)
`1.011(2 x 800 mg)
`4.49 (2 x 1600 mg)
`80—150
`01—0 08
`0-
`-
`002—0 002
`0-0
`~
`__
`0 6
`.
`7-14
`_
`003—03
`0,025
`0007—002
`1-5
`1_5
`02
`0'
`
`16 7 (6 4-25)
`-
`‘
`c1ofibrate
`40 (19—60)
`Clonazepam
`3 (6—23)
`.
`.
`domdlne
`
`a
`_
`clop1dogrel
`47
`c1
`ate
`orazep
`
`0.6
`0
`11111
`OXBCI
`
`55111—105)
`.
`Clozapme
`
`0.95 (06—13)
`.
`(meme
`
`3-3 (3‘4)
`Codeine
`
`3°
`ColchiCine
`
`3
`r
`. mate
`3
`com"
`e
`
`ColistinSulfate
`Coumarin
`0.8 (05—1-5)
`
`
`
`
`
`2
`6
`5000
`PO
`—
`o
`0.38
`0.8
`0.47-
`0.257
`2.7
`Creatine
`
`NA
`NA
`0.08per
`lnhal
`A:2
`69
`0.01
`0.02
`—
`0.52
`1.35
`CromolynSodium
`
`4
`8
`10
`P0
`—-
`—
`0.55
`0.01
`2.1
`0.038
`18.4
`Cyclobenzaprine
`
`1
`24
`1—5mg/kg
`PO,IV
`NA
`12
`1
`0.15
`0.3
`0.0912
`7.6(6.4-8.7)
`Cyclophosphamide
`—-
`0,24
`1v7mg/kg
`1V,P0
`—
`90
`0.3
`0.01
`7.5
`0.035
`20
`Cycldsporine
`
`
`0.3-1
`24
`2mgkg
`1v
`B:4.5
`13
`1
`0.07
`2.2
`3.15
`0.22
`Cytarabine
`
`NA
`24
`2500—5000
`1v
`—
`—
`0.9
`0.05
`0.05
`0.28
`2.5
`Dalteparin
`
`2—8
`24
`50—300
`PO
`B: 13
`77
`0.95
`0.23
`1.9
`0.0239
`29(22.5-39.3)
`Dapsone
`
`3—4
`6—12
`150—300
`PO
`B:3.3
`65
`0.6
`0.5
`1.6
`0.057
`12(8-14)
`Demeclocycline
`3
`12
`300
`P0
`8:3.34.
`75
`0.7
`0.4
`1.8
`0.051
`13.6
`Demethylchlonetracycline
`
`
`2—3
`12
`10—60
`PO
`—
`—-
`—
`-—
`18.5'
`0.025
`28
`Deramciclane
`
`
`3
`8
`50
`P0
`0.15—0.3
`B:10.2
`8.3
`1
`0.1
`41.9
`0.0401
`17
`Desipramine
`
`—
`12
`0.2
`WM
`—
`NA
`97
`0.8
`0.6
`4.4
`0.0157
`44
`Deslanoside
`
`1
`24
`04—16
`1V,P0,IM
`0.005—0.01
`B:25
`84
`0.81
`0.77
`1.04
`0.193
`3.5(1.8—5.3)
`Dexamethasone
`
`1.5
`8
`100400
`PO
`2.4[1(100mg)
`—
`—
`—
`0.02
`1.13
`0.257
`2.7
`Dexloxiglumide
`
`2
`6—8
`30
`P0
`0.2—0.35
`a:8.3
`—
`0.75
`0.2
`1.1
`02566
`2.7(2—4)
`Dextromethorphan
`
`0.15—1.5
`3—6
`5—20
`IM,1v
`0.005—0.009
`—
`—
`NA
`0.01
`10.1
`0.3
`2.4
`Dezocine
`
`Diazepam
`32.9(27—37)
`0.021
`2.0
`0.005
`1
`97
`13:3.4
`0.1—1
`P0,lv,lM
`2—10
`6-8
`1
`
`Diazoxide
`30(20—40)
`0.023
`0.2
`0.4
`1.0
`91
`A:9.0
`15—25
`PO,IV
`75—500
`8—12
`4
`wuN
`
` AQUESTIVE EXHIBIT 1077 Page 0006'
`
`AQUESTIVE EXHIBIT 1077 Page 0006
`
`spray
`
`P0 12 mg/kg
`
`4.5
`
`1U
`
`1609
`NA
`0.025“
`10—25
`0.1-0.5
`0.01-0.1
`0.4—0.6
`1—7
`0.05—10
`0.5—3
`
`7.2.9.3
`
`0.016c-0.033b (10 mg bid)
`0.047=~0.091h (30 mg bid)
`0075—0160‘1 (60 mg bid)
`
`15.3” (400 mg)
`
`(IM)
`
`(Continued)
`
`
`
`

`

`
`
`”3”“
`.
`Levoflmendan
`Lidocaine
`Lincomycin
`Linezofid
`Lisinopril
`Lithium
`Lomefloxacin
`Loperamide
`.
`.
`L°pinaVirlRit°naW
`Loracarbef
`Lorazepam
`Losanan (active metabolite)
`-
`.
`Lovastatin
`Maprotiline
`Mebendazole
`Meclofenamate
`
`3r
`
`Pharmacokinetic Parameters of Important Drugs (Continued)
`
`Eh]
`"
`
`""
`I("111119
`[1111's]
`a.
`
`26
`1-
`1.8
`5'4
`5
`12
`19.2
`8
`‘1 (7'15)
`55
`1
`13 (8—25)
`2
`7.5
`2.9
`43 (27-58)
`55
`1.3
`
`0.55
`0.39
`'
`0128
`0.139
`°~°53
`0.036
`0‘09
`0‘08
`0.126
`0'7
`0.053
`-
`o 347
`0.092
`0.24
`00161
`0'126
`0.533
`
`0.39
`1.5
`0.4
`0.7
`1 3
`'
`o 8
`I
`1.75
`_
`_
`0 74
`0'6
`1.5
`0.49
`0.17
`75
`51
`_7
`2‘0
`0.33
`
`a
`
`—
`0.1
`0-15
`0.3
`1
`
`1 o
`t
`0.8
`0,4
`0.02
`>0.9
`
`0-01
`0.03
`—
`o 1
`o
`0.02
`
`0.7
`
`f
`
`NA
`0.35
`0-4
`1
`0‘3
`
`1 o
`1
`5
`0.
`—
`o 9
`-
`85
`
`°-
`_
`0.33
`0.05
`0 s
`17
`0.
`~
`1
`
`
`
`98$
`D
`I‘
`Then Bang!
`1....
`
`[*1
`9'“
`mm”
`H
`EPII
`or MEI:
`M
`[”91
`[h]
`[h]
`_
`_
`IV
`
`0.2pg/kg/
`min for 24 h
`20—50 mg/
`.
`kglmln
`500
`10mg/kg
`600
`2H0
`
`30°
`400—1000
`2
`400/100
`200—400
`1_3
`50
`_
`10—80
`75—150
`100
`50
`100
`
`NA
`f
`_
`
`In u510n
`
`N/A
`NA
`
`'
`
`6-8
`
`8—12
`12
`24
`6
`12—24
`fafter
`de ecation
`12
`12
`8
`24
`—
`24
`24
`12
`4-6
`8
`
`2‘4
`#2
`0 5
`7 (6—8)
`
`1.5
`4-5
`4
`1.25
`05—3
`1
`—
`3
`8‘24
`0.5 7
`_
`3.2—;
`_ _
`
`“
`55
`
`31
`72
`_
`
`0
`10
`97
`99
`25
`90
`
`993
`99
`95
`as
`95
`99
`_
`
`IV
`PO,1M
`
`IVInf
`pg,
`P0
`
`P0
`PO
`po
`p0
`P0
`P0
`P0
`_
`P0
`P0
`PO
`po
`_
`
`a: 7.86
`.
`5
`_
`B' 7'
`B: 2.5.4.
`6.7.10.1
`
`NA
`_
`
`—
`_
`—
`
`11.5
`_
`——
`A: 5.5
`a- 10 2
`_
`'
`‘
`
`_
`—
`
`1.5—7
`009—3
`
`0.5.4
`
`0.03—0.04
`
`0.6—1.4 mEq/l
`0 0341
`'
`_
`9 6..
`'
`8" (200 m9)
`14': (400 mg)
`0.02—0.05
`0.280h
`—
`0.015-3 ng/mi
`0 2—0 3
`—
`‘
`'
`_
`_
`
`__ _.
`
`. _
`
`MefenamicAcid
`
`Mefloquine
`
`Melatonin
`
`Meloxicam
`
`Melphalan
`
`
`Memantine
`
`Meperidine
`
`
`Mepindolol
`
`Meprobamate
`
`Meropenem
`
`Metamizol
`
`
`Metformin
`
`Methacycline
`
`Methadone
`
`Methaqualone
`
`Methenamine
`
`Methicillin
`Methocarbamol
`
`Methotrexate
`
`Low Dose Therapy
`High Dose Therapy
`
`Methotrimeprazine
`
`2
`504(312—576)
`0.76
`17(15—20)
`1.1
`70(53—97)
`3.5 (2—4)
`4
`12
`1
`6.9(5—8)
`6.2
`13 (10—16)
`25 (13—47)
`19
`20
`1
`1.2
`8.4
`24
`21
`
`0.347
`0.0013
`0.94
`0.041
`0.6
`0.01
`0.2
`0.17
`0.058
`0.7
`0.01
`4
`0.112
`0.053
`0.0277
`0.0364
`0.3465
`0.693
`0.578
`0.082
`h
`0.0346
`
`1.06
`20
`2.15
`0.14
`—
`—
`4.7
`5.4
`0.7
`0.25
`0.01
`9.3a
`1.8
`3.9
`2.8
`0.6
`0.3
`0.5
`0.4
`p.a.
`29.8
`
`0.52
`0.1
`0
`0.5
`0.0
`0.8
`0.1
`0.7
`0.1
`0.7
`0.95
`1.0
`0.4
`0.3
`0.02
`0.9
`0.75
`0
`0.95
`
`—
`0.9
`0.3
`0.89
`0.5
`1.0
`0.52
`0.7
`0.9
`NA
`1.0
`0.55
`0.7
`0.8
`0.8
`0.8
`0
`1
`0.65
`
`90
`98
`—
`99.4
`87
`45
`64
`50
`0
`2
`20
`0
`79
`85
`81
`40
`—
`25
`
`—
`B:8.6
`—
`—
`—
`—
`B: 8.65
`—
`B: 14
`—
`A: 12.5
`B: 2.8
`B: 3.02,
`B: 8.62
`B:2.4
`B:4.6
`A: 3.01
`—
`A: 4.3
`
`7.49.9.3
`
`0.01
`
`0.5
`
`-—
`
`E:9.15
`
`—
`0.02—1
`—
`—
`0.1—0.3
`—
`0.2—0.6
`0.01—0.04
`5—15
`4—20
`5—20
`0.75”
`1—10
`0.3—1.1
`1—4
`20
`1—6
`—-
`—
`0.005
`2.2
`—
`
`SC,IV
`
`P0
`PO
`PO
`PO
`IV,P0
`P0
`PO,1M,
`PO
`PO
`IV
`|V,PO,
`|M,R
`PO
`PO
`PO,|M,SC
`P0
`PO
`IM,IV
`PO,|V
`1V,IM,PO
`
`250
`250—1250
`2—50
`75—15
`0.2 mg/kg
`10
`50—150
`2.5—10
`400
`250—1000
`7—15 mg/kg
`500
`125
`2.5—10
`300
`1000
`1000
`500—1000
`12—18mg/m2
`
`6 days
`
`6
`168
`24
`24
`8for
`12
`3—4
`24
`8
`8
`4
`12
`6
`6—8
`24
`6
`4
`6
`24for
`
`5 days
`
`2—4
`15(8—21)
`1
`4-5
`
`—
`
`5 (3—8)
`1.25
`1.5
`1.5
`NA
`1—1.5
`3.5
`5
`3
`—
`—
`—
`1—2
`1—4
`
`1M
`
`10—30
`
`4—6
`
`—-
`
`wG
`
`(Continued) N
`
`
`
`|
`AQUESTIVE EXHIBIT 1077 Page 0007
`AQUESTIVE EXHIBIT 1077 Page 0007,
`
`

`

`
`
`
`
`
`
`Pharmacokinetic Parameters of Important Drugs (Continued)
`
`Ther. Range
`D
`1-
`'M
`Epg
`or MEC
`h
`onus
`113
`k'i'n‘i'Eirs
`1121ng
`5..
`1
`1%]
`pk.
`lug/ml}
`U“
`m]
`"'1
`l ]
`0.25-1.5
`
`NA
`_
`P0
`0.2—0.25
`24
`.
`.
`35
`0.019
`4.5
`0.8 after
`0.85
`27
`Methyldlgoxm
`demethyl-
`ation
`0.7
`
`Methyldopa
`Methylphenidate
`l-form
`“on"
`
`Gen-Methylprednisolone
`Metoclopramide
`Metoprolol
`Meuonidazole
`
`Mexiletine
`Mezlocimn
`Mianserin
`Mibefradil
`Miconazole
`
`Midazolam
`
`1.7
`
`0.4
`
`0.5
`
`-
`366
`
`1.5 (1 .3—3.1)
`2.7
`3.2 (3—34)
`8.0 (8—14)
`
`15 (9—20)
`M (0.64 ‘6)
`23
`21 (1 745)
`22.5 (20—25)
`
`'
`31:
`
`046
`0.257
`0.2165
`0.087
`
`0.046
`0,855
`0.03
`”33
`00308
`
`'
`1:
`
`°-41
`2.4
`4.2
`0.75
`
`5.3
`0.38
`40
`2'2 (1'8“2'7)
`21
`
`3
`
`0'1
`0.17
`0.1
`0.08
`
`0.1
`0.5
`—
`0'03
`0.01
`
`0.4
`. 2
`'
`g :2
`
`1'0
`0 4
`.
`0.45
`0.8
`
`0.9
`0
`0.3
`0'9
`0.3-0.6
`
`1.2
`
`0.24
`
`3.3 (0.9—6.6)
`
`0.75
`
`NA
`
`2
`‘2 (1°46)
`
`0.18
`0 43
`'
`
`0.95
`0 1
`'
`
`0.7-1
`0.9
`
`—
`
`20
`—
`—
`
`—
`_
`—
`
`0.03—4
`_
`—
`_
`
`PO.|V
`'
`PO W
`PO.N
`po
`
`500-2000
`10—40
`1040
`4.48
`
`5‘12
`12-24
`12—24
`24
`
`85
`30
`
`13
`15
`
`70
`50
`90
`99
`92
`
`95
`
`4
`76
`
`47
`
`2‘6
`B: 7.32
`
`9: 9.7
`B: 25
`.
`.
`B. 9.05
`A. 2.72
`—
`_
`.65
`
`:
`B 6
`,
`-
`B. 6 15
`
`_
`
`13: 2.8.5,
`7.8
`
`—
`
`lVJM-PO
`
`0025—01
`1—8
`
`_
`0.5—2
`5 500
`0.02—0.07
`_
`0.001-10
`
`0.04—0.12
`
`_
`
`0.5—10
`
`P0
`PO.|V
`
`PO'N
`IV.|M
`P0
`P0
`IV
`PO
`MN
`
`P0
`
`PO.|V
`
`1°
`103—200
`k
`IV 7.5 mg/ 9
`PO 250
`300
`1500—400
`200—
`200
`30-
`50—100
`1200
`100-
`100-500
`_
`2 5
`
`0
`
`50—100
`
`10°
`
`—
`
`0.0004—1.8
`
`PO
`
`600—1200
`
`8
`12
`6
`8
`8
`6
`24
`24
`6
`1244
`1 ’1
`before
`surgery
`8
`
`‘2
`
`12
`
`5
`
`(4—6)
`
`2.3
`3.2
`2.5
`0 75
`'
`1 5
`1 3
`'
`1
`2
`—
`_
`1-5
`NA
`2.5
`0.75(1M)
`
`2-3
`2
`
`(’75
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`Migntol
`Minocycline
`iocamycm
`M-
`.
`
`
`
`0.347
`8
`0'05
`-
`0 7
`
`1
`
`4
`
`'
`0 05
`
`._._
`
`.
`
`11
`
`Minazapine
`
`Misoprostol
`Moclobemide
`Modafinil
`
`21.5
`0.45 (0.3—0.6)
`1
`11.3
`
`5.5
`4.45
`4.6
`2.511.5-35)
`2.3 (1.5—4)
`2.4
`
`12
`22.5
`14.1
`0.5 (05—1)
`1.6
`10.8
`
`0.8 (0.7—0.9)
`17.1 (12—26)
`4.9
`2.0 (1.6—3)
`3.5 (2—5)
`4.3 (3.5—5)
`2.5
`
`0.032
`1.5
`0,7
`0.061
`
`0.24
`0.156
`0.151
`0.3
`0.3
`0.289
`
`0.058
`0.03
`0.049
`1.386
`0.433
`0.064
`
`0.866
`0.039
`0,14
`0.35
`0.2
`0.161
`0.277
`
`10.3
`3.5
`1
`0.793
`
`0.7
`4.7
`0.14
`4
`1.0
`1.3
`
`1.85
`0.15
`2.1
`0.3
`0.26-0.45
`3.9
`
`2.8
`0.12
`2,3
`0.14
`0.5
`2.6a
`0.2
`
`0.04
`0.01
`0.005
`0.05
`
`0.01
`—
`0
`0.01
`0.1
`0.55
`
`0.2
`0.8
`0.7
`0.38
`0.14
`0.05
`
`0
`0.1
`—
`0.05
`0.55
`0.02
`0.5
`
`0.5
`0.8
`0.4
`—
`
`0.13
`0.01
`0.64
`0.4
`0.4
`0
`
`0.9
`0.8
`0.4
`0.5
`—-
`NA
`
`0.2
`1
`0.7
`0,73
`0.2
`—
`0.03
`
`Moexipril
`Mometasone Furoate
`Montelukast
`Moricizine
`Morphine
`Moxalactam
`
`Moxifloxacin
`Nabumetone
`Nadolol
`Nafcillin
`Naiidixic Acid
`Nalmefene
`
`Naloxone
`Naproxen
`Naratriptan
`Nateglinide
`Nefazodone
`Nelfinavir
`Neomycin
`
`
`
`
`
`85
`85
`50
`60
`
`50
`—
`99
`95
`35
`50
`
`50
`99
`30
`90
`93
`45
`
`—
`99
`30
`98
`99
`98
`—
`
`—
`—
`B: 63
`—
`
`—
`—-
`—
`B: 6.4
`B: 8.05
`2.57.7,
`10.2
`
`—
`—
`9: 9.67
`A: 2.65
`A: 1.6
`76
`
`B: 7.94
`A15
`—
`—
`—
`—
`—
`
`—
`0.1-1000
`00006—028
`4.8-7»
`1.3
`
`0.015—0.25
`—
`0.3h
`00006-08
`007-01
`20—100
`
`4.5h
`—
`0025—0275
`0.03-1
`5—50
`—
`
`0.01—0.03
`30-50
`—
`5.6h
`0.05—0.18
`3.4b
`5-10
`
`PO
`P0
`PO,|V
`P0
`
`P0
`Inhal
`P0
`PO
`|V,|M.SC
`mm
`
`PO
`P0
`P0
`1V,|M,PO
`PO
`IV,|M,SC
`
`IV
`PO
`P0
`PO
`PO
`PO
`PO
`
`15-30
`0.2
`300-600
`200
`
`7.5-30
`0.4
`10
`250
`10
`700-2000
`
`400
`1000-2000
`80—240
`500
`1000
`0.5—2
`
`0.4—2
`275
`2.5
`120
`200-300
`750
`1000—2000
`
`24
`6
`23-12
`24
`
`12-24
`—
`24
`8
`4
`8
`
`24
`24
`24
`4—6
`6
`single
`dose
`
`2.5
`0.25
`1
`1-2
`
`1.5
`2
`2-4
`1 (0.5—2)
`3
`—
`
`1-3
`9-12
`3
`1
`1—2
`IM 23
`SC 1.5
`
`as needed
`6—8
`24
`8
`12
`8
`6
`
`NA
`2.5
`2.5 (1.5—4)
`0.8
`1
`2-4
`1-4
`(Continued)
`
`13.3so
`
`'
`AQUESTIVE EXHIBIT 1077 Page 0008
`
`..__ .—
`
`,
`
`-
`
`.J.
`
`1..
`
`“as: 3: 7
`
`—._¢.._.. ,9. “gm—.5
`
`u --:.
`
`2
`
`-
`
`-— wag
`
`1-—-
`
`—
`
`-
`
`