WOLFGANGA. RITSCHEL
`
`GREGORY L. KEARNS
`
`HANDBOOKof
`
`BASIC PHARMACOKINETICS
`
`AQUESTIVE EXHIBIT 1077 Page 0001
`
`..INCLUDING CLINICAL APPLICATIONS
`
`SIXTH EDITION
`
`AQUESTIVE EXHIBIT 1077 Page 0001
`
`

`

`Handbook
`
`of
`
`Basic
`
`Pharmacokinetics
`
`... including Clinical Applications
`
`Sixth Edition
`
`WolfgangA.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
`
`GregoryL. Kearns
`Pharm.D., Ph.D., F.C.P.
`
`Marion Merrell Dow/Missouri Chairin Pediatric Pharmacology
`Professor ofPediatrics and Pharmacology
`University ofMissouri—KansasCity
`Chief, Division ofPediatric Pharmacology and Medical Toxicology
`Director, Pediatric Pharmacology Research Unit
`Children’s Mercy Hospitals and Clinics
`Kansas City, Missouri
`
`APhA
`
`AMERICAN PHARMACISTS ASSOCIATION
`WASHINGTON,D.C.
`
`ist shall not be deemed,
`ich patent or trademark.
`m mayexercise the same
`mer.
`wrticular knowledgethat
`inclusion be interpreted
`snot been included does
`Further, no official sup-
`y is intended or inferred.
`sarch andclinical experi-
`ig therapy must be based
`reflected in theliterature
`
`pleteness of the informa-
`onsible for the continued
`s information. Therefore,
`-o claims,loss, or damage
`herein.
`
`AQUESTIVE EXHIBIT 1077 Page 0002
`
`AQUESTIVE EXHIBIT 1077 Page 0002
`
`

`

`
`
`
`AcquiringEditor: Julian I. Graubart
`ManagingEditor: 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.
`
`Nopart ofthis 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 permissionfrom thepublisher.
`To commenton this bookvia e-mail, send your messageto the publisher at aphabooks@aphanet.org.
`Library ofCongress Cataloging-in-Publication Data
`
`Ritschel, W. A. (Wolfgang A.)
`Handbookofbasic pharmacokinetics— includingclinical applications/
`Wolfgang A.Ritschel, Gregory L. Kearns.— 6th ed.
`p.;cm.
`Includes bibliographical references and index.
`ISBN 1-58212-054-4
`1, Pharmacokinetics—Handbooks, manuals,etc. 2. Clinical
`pharmacology——Handbooks, manuals,etc.
`{[DNLM:1. Pharmacokinetics—Handbooks. QV 39 R612h 2004] I. Kearns,
`Gregory L.II. American Pharmaceutical Association.IILTitle.
`
`RM301.5.R57 2004
`615.7—dc22
`
`2003026662
`
`
`
`Howto Order This Book
`Online: www.pharmacist.com
`
`By phone: 800-878-0729 (from the United States and Canada)
`
`VISA®, MasterCard®, and American Express® cards accepted
`
`
`
`
`
`AQUESTIVE EXHIBIT 1077 Page 0003
`AQUESTIVE EXHIBIT 1077 Page 0003
`
`

`

`Appendix
`Pharmacokinetic Parameters of
`Important Drugs
`
`Pharmacokinetic data have becomeanintegral part ofthe pharmacologic characterization
`of a drug. Regulatory agencies require determination of pharmacokinetic data in Phase I
`studies and submission ofpharmacokinetic drug data as part of a New Drug Application.
`For research and development, pharmacokinetic drugdata are used in design ofnew
`chemicalentities based on structure-activity relationships, andfor design ofproper dosage
`formsto result in the desired therapeutic concentrations.
`Clinically, pharmacokinetic data are usedforthe design ofdosage regimensin drug-
`naive patients, for drug monitoring, and for dosage regimen adjustment. Furthermore,
`pharmacokinetic data give information or indications whethera drug maybe excreted in
`milk (pK,), whether the half-life may change in renal impairment or advanced age (Fy),
`and whetherprotein binding maybeofclinical importance regarding displacement, hypo-
`and hyper-albuminemia (if EPB > 80 percent), etc.
`Datalisted in the appendix have been compiled andextracted from morethan a thou-
`sand publications. Hence,it is not possible for reasonsofspace to give a listing of refer-
`ences. The data have beenlisted as mean data. Reports are often conflicting, contradictory,
`or at least show widevariations amonginvestigators. This,in part, is due to different ana-
`lytical methods employedfor drugassay,different population groups,and different exper-
`imental conditions.
`Onlytheelimination half-life rangesarelisted for many drugs. This should be indica-
`tive that a calculated dosage regimen basedonliterature mean data may notresult 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 ofa
`drug. Again, drug monitoringin such situations may become important.
`The following symbols are used:
`
`tin
`k, or B
`Va
`
`= elimination (terminal) half-life
`= terminal disposition rate constant
`= apparent volumeofdistribution (Vag Or Va area)
`
`367
`
`AQUESTIVE EXHIBIT 1077 Page 0004
`
`AQUESTIVE EXHIBIT 1077 Page 0004
`
`

`

`
`
`368 APPENDIX
`
`AQUESTIVE EXHIBIT 1077 Page 000 Ther.Range
`
`F,
`f
`
`URA
`
`D
`
`t
`tax
`NA
`—
`a
`8
`.
`e
`
`f
`8
`
`= 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
`EPB
`Ther. Range or MEC = therapeutic range or minimum effective concentration
`Note: For antimicrobial agents the MEC or MIC (minimuminhib-
`itory concentration) dependson thesensitivity of the micro-
`organism. Hence, a sensitivity test may be more appropriate than
`a listed mean value.
`= usual route of administration.This listing is not exhaustive. Even
`if not listed, the drug may be used by otherroutes.
`= dosesize usually employed as maintenancedose. Loading doses are
`notlisted.
`= dosinginterval for multiple dosing
`= time to reach the peak upon extravascular administration
`= Notapplicable
`= Data notavailable
`™ V./f
`= Coax OF Crrex
`as Cnin or Cain
`= if required, repeat dose after 2h
`= pmol/L
`= poor metabolizer
`= effective concentration 50% = ECs,
`
`‘tax ret
`
`orMECD?IDAFaneowtrh
`
`Twndewll
`
`abl
`
`EPB Font
`
`kaorBVaffl
`
`th-11
`
`ty hl
`
`
`
`nacokineticParametersofImportantDrugs
`
`AQUESTIVE EXHIBIT 1077 Page 0005
`
`DRUG
`
`€
`

`

`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`Pharmacokinetic Parameters of Important Drugs (Continued)
` Ther. Range
`tua — Wit
`x
`EPB
`or MEG
`thi
`fh]
`9
`.
`5.6
`;
`ss
`0.124
`1.9
`0.
`ti
`0.062
`—_
`=
`2.8(2-3)
`0.248
`1.
`;
`14
`=
`eS
`0.048
`277
`0.026
`98.9°
`<0.03
`
`f
`ae
`09
`4ia
`03
`:
`-
`
`1%]
`90
`=
`=<
`a
`
`Pk, =
`PO
`_
`is
`B:7.72
`ane VAGovula
`PO
`es
`0.028
`VAGcre
`=
`:
`ain
`_
`oa
`PO
`1.0°(2x800mg)
`(2 x 400 mg)
`4.4? (2 x 1600 mg)
`0.01-0.
`80-150
`ali
`0.0002-0.
`2-0.002
`me
`.
`06
`7-14
`~
`003-08
`0.025
`0.007-0.02
`1-5
`02
`15
`o
`
`ak
`
`PO
`PO
`PO
`PO
`PO
`ay
`ro
`PO,IV
`PO,IM,5'
`c
`PO,IV
`PO,IV,IM
`PO,IV
`IM,PO
`
`°
`mal
`
`200-40
`°
`100
`150-450
`100
`400-1600
`
`500
`1-2
`0.15-0.3
`15
`i560
`125-450
`me
`5-30
`ox
`30
`a
`2.5-5mg/kg
`WV10-25
`1.5 ma/ka
`PO30
`
`-
`thi
`
`12
`:
`24
`3
`24
`i
`
`ih
`kn
`8-12
`2
`24
`=
`24
`ingle
`‘Sit
`24
`638
`'
`612
`8
`‘
`12
`
`1500-3)
`te
`thi
`5(4
`a5
`men
`
`2
`3
`2
`1
`=“
`j
`4
`1
`1.25
`1(0.5-2)
`2
`bi
`_
`s
`
`0.041
`0.017
`0.086
`0.086
`1.155
`0.0147
`,
`0.0126
`0.7.
`3
`0.21
`0.02
`0.231
`0.231
`0.8662
`
`0.15
`0.12
`ii ane
`0
`:
`3.5
`0.3
`_
`=
`0.4
`0.35
`1
`3.5 (2-5)
`_
`—
`ve
`04
`2
`2.4
`0.7
`0.15
`.
`:
`6.7
`.
`0.55
`0.8
`OA
`075
`47
`0
`:
`
`0.75
`1
`08
`,
`05
`:
`1
`os
`1
`:
`05
`0.44
`11M.
`11M.
`0.04
`
`47-82
`95
`20
`98
`i
`a
`90
`40
`40-25
`40
`5
`2
`0
`35
`
`B:4.5
`A: 2.95
`B:8.3
`=
`2;
`A:29
`=
`B:
`8.
`36
`B:
`8.
`28.1
`B: 1.7,
`12.4
`=
`—
`NA
`
`DRUG
`Clinafloxacin
`Clindamycin
`;
`i
`Clodronate
`16.7
`(6.
`Clofibrate
`6.7 (6.4-25)
`Clonazepam
`40 (19-60)
`Clonidine
`8 (6-23)
`Pr
`Clopidogrel
`8
`;
`ee
`a7
`ate
`es
`Cloxacillin
`Clozapine
`55 (11-105)
`'
`Cocaine
`0.95 (0.6-1.3)
`i
`
`serene
`ae
`
`Colchicine
`30
`_
`
`
`oeaaee
`3
`3
`listimethate
`e
`
`ColistinSulfate
`Coumarin
`0.8 (0.5-1.5)
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`2
`6
`5000
`PO
`-
`0
`0.38
`08
`0.47
`0.257
`27
`Creatine
`NA
`NA
`0.08per
`Inhal
`A:2
`69
`0.01
`0.02
`_
`0.52
`1.35
`CromolynSodium
`4
`8
`10
`PO
`_
`-
`0.55
`0.01
`2.1
`0.038
`18.4
`Cyclobenzaprine
`1
`24
`1-5mg/kg
`POV
`NA
`12
`1
`0.15
`08
`0.0912
`7.6(6.4-8.7)
`Cyclophosphamide
`_
`8,24
`V7mghkg
`V,PO
`_
`90
`0.3
`0.01
`75
`0.035
`20
`Cyclosporine
`0.3-1
`24
`2mg/kg
`Vv
`B:4.5
`13
`1
`0.07
`2.2
`3.15
`0.22
`Cytarabine
`NA
`24
`2500-5000
`Nv
`_
`=
`0.9
`0.05
`0.05
`0.28
`2.5
`Dalteparin
`2-8
`24
`50-300
`PO
`B:13
`7
`0.95
`0.23
`1.9
`0.0239
`29(22.5-39.3)
`Dapsone
`344
`6-12
`150-300
`PO
`B:3.3
`65
`0.6
`0.5
`1.6
`0.057
`12(8-14)
`Demeclocycline
`3
`12
`300
`PO
`B:3,34,
`75
`07
`0.4
`1.8
`0.051
`13.6
`Demethyichlortetracycline
`2-3
`12
`10-60
`PO
`_
`_
`_-
`_
`18.52
`0.025
`28
`Deramciclane
`3
`8
`50
`PO
`0.15-0,3
`8:10.2
`8.3
`1
`0.1
`419
`0.0401
`17
`Desipramine
`-
`12
`0.2
`VIM
`_
`NA
`97
`08
`0.6
`44
`0.0157
`44
`Deslanoside
`1
`24
`0.4-16
`(V,PO,IM
`0.005-0.01
`B:25
`84
`0.81
`0.77
`1.04
`0.198
`3.5(1.8-5.3)
`Dexamethasone
`15
`8
`100-400
`PO
`2.4(100mg)
`_
`—
`_
`0.02
`1.42
`0.257
`27
`Dexloxigiumide
`2
`68
`30
`PO
`0.2-0.35
`B:8.3
`_
`0.75
`0.2
`14
`0.2566
`2.7(2-4)
`Dextromethorphan
`Dezocine
`24
`0.3
`10.1
`0.01
`NA
`_
`_
`0.005-0.009
`IM,IV
`5-20
`346
`0.15~1.5
`Diazepam
`32.9(27-37)
`0.021
`2.0
`0.005
`1
`97
`B:3.4
`0.1-1
`PO,IV,IM
`2-10
`6-8
`1
`Diazoxide
`30(20-40)
`0.023
`0.2
`0.4
`1.0
`1
`A:9.0
`15-25
`PO,IV
`75-500
`8-12
`4
`
`
`Spray
`
`PO 12 mg/kg
`
`45
`
`tu
`
`160°
`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
`
`0.016*-0.033(10 mg bid)
`0.047°~0.091» (30 mgbid)
`0.0750. 160° (60 mg bid)
`
`15.3(400 mg)
`
`(im)
`
`w~“
`AQUESTIVE EXHIBIT 1077 Page 0006
`AQUESTIVE EXHIBIT 1077 Page ca
`6
`
`(Continued)
`
`

`

`
`
`Mefenamic Acid
`
`Mefloquine
`i
`Melatonin
`Meloxi
`
`icam
`
`Melphaian
`emantine
`.
`ever
`
`leperidine
`
`Mepindolol
`
`Meprobamate
`
`Meropenem
`
`Metamizol
`
`Metformin
`;
`
`Methacycline
`Methadone
`Methaqualone
`
`Methenamine
`Methicillin
`Methocarbamol
`
`Methotrexate
`
`Low Dose Therapy
`High Dose Therapy
`
`Methotrimeprazine
`PI
`
`5
`
`2
`04 (312-576)
`0.76
`17 (15-20)
`rr
`70 (53-97)
`3.5 (2-4)
`4
`12
`1
`6.9 (5-8)
`62
`S
`13(10-16)
`25(13-47)
`is
`20
`1
`12
`8.4
`24
`21
`
`0.347
`0.0013
`0.94
`0.041
`06
`.
`0.01
`0.2
`0
`17
`0.058
`.
`0.7
`ay
`is
`4
`01
`112
`9.053
`0.0277
`igtte
`.
`0.3465
`.
`0.693
`,
`0.578
`0.082
`h
`0.0346
`
`9.38
`18
`:
`3.9
`ta
`’
`0.6
`“
`03
`.
`05
`0.4
`pa
`-
`29.8
`
`1.06
`20
`2.45
`oa
`_
`~
`47
`5.4
`07
`g
`0.25
`ia
`.
`
`0.52
`01
`0
`Fe
`a
`.
`08
`0.1
`0.7
`01
`.
`0.7
`9s
`.
`
`_
`09
`a3
`.
`‘in
`0.5
`1%
`0.52
`07
`0.9
`NA
`1.0
`
`1.0
`04
`:
`a3
`00
`.
`0
`.
`0.75
`i
`F
`0.95
`
`0.55
`07
`A
`i
`0.8
`0.8
`
`0
`:
`0.65
`
`90
`98
`_
`hea
`:
`87
`43
`64
`50
`0
`2
`20
`
`0
`79
`85
`a1
`40
`_
`25
`
`~
`HEE
`8,
`om
`_
`==
`_
`nee
`8
`=
`:
`ara
`ee
`i
`AL12.5
`B: 2.8
`B: 3.02,
`7.49,9.3
`“
`B: 8.62
`is
`B: 2.4
`"
`B: 4.6
`nae
`A: 3.01
`~
`A:43
`
`0.01
`
`05
`
`—
`
`B:9.15
`Bie
`
`55
`1
`
`13 (8-25)
`2
`75
`
`0.126
`0.7
`
`0,053
`0.347
`0.092
`
`0.747
`0.6
`
`1.5
`0.49
`0.17
`
`0.02
`>0.9
`
`0.01
`0.03
`_
`
`_
`0.9
`
`0.85
`0.33
`—
`
`0.05
`0.1
`75
`0.24
`2.9
`0.8
`0.02
`51.7
`0.0161
`43 (27-58)
`5.5
`0.126
`2.0
`0
`0.17
`
`13
`0.533
`0.33
`0.7
`1
`
`99
`25
`
`90
`99
`99.8
`
`95
`88
`95
`99
`_
`
`-
`-
`
`11.5
`—
`_
`
`A:5.5
`B: 10.2
`=
`-
`—
`
`9.6%
`8° (200 mg)
`14* (400 mg)
`0.02-0.05
`0.2805
`=e
`
`0.015-3 ng/ml
`0.2-0.3
`=>
`_
`—
`
`PO
`PO
`
`PO
`PO
`=
`
`PO
`PO
`PO.
`PO
`—
`
`400/100
`200-400
`
`Lal
`50
`_—
`
`10-80
`75-150
`100
`50
`100
`
`6
`12-24
`after
`defecation
`12
`12
`
`8
`24
`=
`
`24
`24
`12
`46
`8
`
`4
`1.25
`
`0.5-3
`1
`—
`
`3
`8-24
`0.5-7
`0.5-2
`0.5-2
`
`Lithium
`Lomefloxacin
`Loperamide
`
`Lopinavir/Ritonavir
`Loracarbef
`
`Lorazepam
`Losartan (active metabolite)
`
`Lovastatin
`Maprotiline
`Mebendazole
`Meclofenamate
`
`zs
`
`PO
`Pt
`0
`PO
`PO
`\V,PO
`ss
`PO,IM,
`SGIv
`PO
`PO
`Vv
`IV,PO,
`IMR
`Po
`PO
`
`PO,IM,SC
`PO
`PO
`IM,IV
`
`PO,IV
`Ml
`IM,PO
`
`250
`250-1250
`7
`2-50
`75-15
`0.2 mg/kg
`10
`50-150
`2.5-10
`400
`250-1000
`7-15 mg/kg
`_
`125
`2.5-10
`300
`1000
`1000
`500-1000
`12-18 mg/m?
`
`6
`168
`24
`24
`8 for
`6 days
`12
`34
`24
`8
`8
`4
`12
`6
`6-8
`24
`6
`4
`°
`24 for
`Om
`
`2-4
`15 (8-21)
`1
`45
`=H
`5 (3-8)
`1.25
`15
`15
`=
`NA
`are
`35
`5
`3
`=
`=
`—
`"
`1-4
`
`wo
`
`e
`=|
`
`IM
`
`10-30
`
`4-6
`
`_
`
`(Continued)
`
`—
`Si
`.02-
`=
`_
`0.1-0.3
`_
`0.2-0.6
`io
`.01-0.04
`5-15
`420
`5-20
`0.75»
`,
`1-10
`
`0.3-1.1
`1-4
`20
`1-6
`~
`-
`0.005
`2.2
`
`=
`
`_AQUESTIVE EXHIBIT 1077 Page 0007
`AQUESTIVE EXHIBIT 1077 Page 0007
`
`
`
`
`
`Pharmacokinetic Parameters of Important Drugs (Continued)
`
`DRUG
`
`Levosimendan
`
`Lidocaine
`
`Lincomycin
`Linezolid
`
`Lisinopril
`
`‘ta
`(h]
`
`1.26
`
`1.8
`
`5.4
`5
`
`12
`
`19.2
`8
`11 (7-15)
`
`ky or B
`th="]
`
`0.55
`
`0.39
`
`0.128
`0.139
`
`0.058
`
`0.036
`0.09
`0.063
`
`Ma
`[kg]
`
`0.39
`
`1.5
`
`04
`0.7
`
`1.8
`
`0.8
`1.75
`_
`
`Fa
`
`_
`
`0.1
`
`0.15
`0.3
`
`1
`
`1.0
`0.8
`0.4
`
`f
`
`NA
`
`0.35
`
`0.4
`1
`
`0.3
`
`1.0
`1
`0.5
`
`
`Ther. Range
`EPB
`or MEC
`DB
`t
`Tax
`
`[7%]
`pk,
`[eg/mi]
`URA
`[mg]
`{hl
`th]
`
`_
`
`66
`
`72
`31
`
`=
`
`0
`10
`97
`
`_
`
`B: 7.86
`
`B:7.S
`—
`
`-
`
`1.5-7
`
`0.09-3
`0.5-4
`
`B: 2.5,4,
`6.7,10.1
`
`0.03-0.04
`
`NA
`_
`_
`
`0.6-1.4 mEq/l
`0.03-4
`—
`
`Vv
`
`Vv
`
`PO,IM
`IV Inf
`PO
`
`PO
`
`PO
`PO
`PO
`
`0.2 pa/kg/
`min for 24h
`
`NA
`
`Infusion
`
`6-8
`B12
`12
`
`24
`
`20-50 mg/
`kg/min
`500
`10 mg/kg
`600
`
`20-40
`
`300
`400-1000
`2
`
`N/A
`
`NA
`
`24
`0.5
`1-2
`
`7 (6-8)
`
`=
`15
`45
`
`98E
`
`|
`
`

`

`
`
`
`Ther. Range
`D
`t
`tax
`Vv,
`EPB
`or MEC
`th)
`{bl
`DRUG
`i
`‘re
`tvkgl
`Fa
`f
`(%]
`pk,
`{ug/ml
`URA
`ui
`
`0.2-0.25
`24
`0.25-1.5
`27
`NA
`=
`PO
`igoxi
`36
`0.019
`45
`O8after
`0.85
`Methyldigoxin
`demethy!-
`ation
`
`
`
`5 (4-6)
`23
`32
`as
`ca
`.
`is
`1-3
`
`12
`
`PO,IV
`
`500-2000
`
`PO,IV
`PO,IV
`PO
`1V,1M,PO
`PO
`PO,IV
`
`PO,IV
`
`10-40
`10-40
`448
`10
`100-200
`V7.5 mg/kg
`PO 250
`200-300
`
`612
`=
`12-24
`12-24
`a
`8
`12
`6
`8
`8
`
`Methyldopa
`.
`Methylphenidate
`d-form
`|-form
`6-Methylprednisotone
`Metoclopramide
`Metoprolol
`Metronidazole
`
`Mexiletine
`Mezlocillin
`Mianserin
`Mibefradil
`Miconazole
`
`1.7
`
`f
`3.6
`1.5(1.3-3.1)
`27
`3.2 (33.4)
`8.0 (8-14)
`
`15(9-20)
`0.8(0.6-1.6)
`23
`21 (17-25)
`22.5 (20-25)
`
`0.4
`
`oe
`0.19
`0.46
`0.257
`0.2165
`0.087
`
`0.046
`0.866
`0.03
`0.033
`0.0308
`
`0.5
`
`ae
`18
`0.44
`24
`4.2
`0.75
`
`5.3
`0.38
`40
`2.2 (1.8+2.7)
`21
`
`0.7
`
`:
`0
`0.
`0.17
`0.1
`08
`0
`
`A
`a5
`-
`0.03
`1
`0.0
`
`0.4
`
`tie
`0.22
`0
`oi
`4
`0.
`45
`0.
`0.8
`.
`
`o8
`0
`
`0.3
`0.9
`0.3-0.6
`3-0.
`
`20
`
`2
`=
`85
`30
`13
`15
`
`zo
`50
`90
`99
`92
`
`oe
`
`=
`E,
`26
`"
`B: 7.32
`ea
`B:9.7
`19.
`B: 2.5
`
`5
`Bye03
`A: 2.72
`i
`4
`_
`B: 6.65
`
`0.03-4
`2
`
`S25
`=
`=
`_
`0.025-0.1
`1-8
`
`0.5-2
`
`5-500
`0.02-0.07
`_
`0.001-10
`
`
`
`Midazolam 0.24«=.1.2 3,3 (0.9-6.6) 0.75 NA 95 B: 6.15 0.04-0.1 bape
`
`
`
`
`
`
`
`
`
`2
`
`0.347
`
`0.7-1
`0.9
`
`4
`76
`
`_
`
`~
`
`0.5-10
`
`PO
`
`PO,WV
`
`50-100
`100
`
`2-3
`2
`
`
`
`
`
`
`
`
`6
`1500-4000
`1V,IM
`_
`
`24
`30-200
`PO
`=
`
`24
`50-100
`PO
`15
`
`:
`6
`400-1200
`Vv
`N
`
`12-24
`100-500
`PO
`25
`.75
`(IM)
`1h
`2-5
`IM.V
`12
`:
`0.75 (
`
`
`
`
`
`surgery
`
`8
`
`12
`
`
` Pharmacokinetic Parameters of Important Drugs (Continued)
`
`13
`24
`400
`PO
`4.5"
`—
`50
`0.9
`0.2
`1.85
`0.058
`12
`Moxifloxacin
`912
`24
`1000-2000
`PO
`es
`_
`99
`0.8
`0.8
`0.15
`0.03
`22.5
`Nabumetone
`
`
`
`
`
`
`
`
`Nadolol B:9.67 —0.025-0.27514.1 0.049 241 0.7 0.4 30 PO 80-240 24 3
`
`
`
`Nafcillin
`0.5 (0.5-1)
`1.386
`0.3
`0.38
`0.5
`90
`A: 2.65
`0.03-1
`1V,IM,PO
`500
`46
`1
`Nalidixic Acid
`1.6
`0.433
`0.26-0.45
`0.14
`—
`93
`A: 1.6
`5-50
`PO
`1000
`6
`1-2
`Nalmefene
`10.8
`0.064
`3.9
`0.05
`NA
`45
`716
`=
`1V,IM,SC
`0.5-2
`single
`IM 2.3
`dose
`$c 15
`
`0.4-2
`IV
`0.01-0.03
`B: 7.94
`—
`0.2
`0
`28
`0.866
`0.8(0.7-0.9)
`Naloxone
`275
`PO
`30-50
`ASS
`99
`1
`0.1
`0.12
`0.039
`17.1(12-26)
`Naproxen
`2.5
`PO
`_
`—
`30
`0.7
`—
`aa
`0.14
`49
`Naratriptan
`120
`PO
`5.6
`—
`98
`0.73
`0.05
`0.14
`0.35
`2.0 (1.6-3)
`Nateglinide
`200-300
`PO
`0.05-0.18
`=i
`99
`0.2
`0.55
`0.5
`0.2
`3.5 (2-5)
`Nefazodone
`Nelfinavir
`4.3 (3.5-5)
`0.161
`2.6
`0.02
`—
`98
`=
`3.4
`PO
`750
`
`Neomycin
`25
`0.277
`0.2
`0.5
`0.03
`_
`-
`5-10
`PO
`1000-2000
`
`as needed
`68
`24
`8
`12
`8
`6
`
`NA
`25
`2.5 (1.5-4)
`08
`1
`24
`14
`(Continued)
`
`w©
`
`AQUESTIVE EXHIBIT 1077 Page 0008
`AQUESTIVE EXHIBIT 1077 Page 0008
`
`sateen
`ero
`_
`=
`alee
`
` aS SSS ee aaLee si aeee =
`
`Mialitol
`Wglito
`Minocycline
`
`Miocamycin
`
`Mirtazapine
`Misoprostol
`Moclobemide
`Modafinil
`
`Moexipril
`Mometasone Furoate
`Montelukast
`Moricizine
`Morphine
`Moxalactam
`
`12 (10-16)
`
`1
`
`21.5
`0.45 (0.3-0.6)
`1
`13
`
`5.5
`4.45
`46
`2.5 (1.5-3.5)
`2.3 (1.5-4)
`2.4
`
`0.058
`
`0.7
`
`0.032
`15
`0.7
`0.061
`
`0.24
`0.156
`0.151
`0.3
`0.3
`0.289
`
`0.18
`0.43
`\
`
`4
`
`10.3
`35
`1
`0.79"
`
`0.7
`47
`0.14
`4
`1.0
`13
`
`0.95
`0.1
`-
`
`0.05
`
`0.04
`0.01
`0.005
`0.05
`
`0.01
`—
`0
`0.01
`0.1
`0.55
`
`a
`
`0.5
`0.8
`0.4
`=
`
`0.13
`0.01
`0.64
`0.4
`0.4
`0
`
`B: 2.8.5,
`oa
`
`~
`
`=
`_
`B: 6.3
`=
`
`_
`_
`~
`B: 6.4
`B: 8.05
`2.5,7.7,
`10.2
`
`proog™[8
`
`7
`
`a
`0.1-1000
`0.0006-0.28
`4.8-7>
`1.36
`
`0.015-0.25
`—
`0.3°
`0.0006-0.8
`0.07-0.1
`20-100
`
`PO
`
`PO.
`PO
`PO,IV
`PO
`
`PO
`Inhal
`PO
`PO
`IV,IM,SC
`1V,1M
`
`at
`
`85
`85
`50
`60
`
`50
`—
`99
`95
`35
`50
`
`600-1200
`
`15-30
`0.2
`300-600
`200
`
`7.5-30
`0.4
`10
`250
`10
`700-2000
`
`12
`
`24
`6
`8-12
`24
`
`12-24
`=
`24
`8
`4
`8
`
`0.75
`
`25
`0.25
`1
`1-2
`
`1.5
`2
`2-4
`1 (0.5-2)
`3
`-
`
`|
`
`