2 of Medicinal Kemistry"” bth Edpbion pik Dawid Ghtlians ¢ Homas Le Cz Pe eids.ar Table A.1. pK, Values for Some Drugs and Miscellaneous Organic Acids and Bases PA, Values: Drugs HA He" Reterence A Acebutolol 92 1 ‘Acenacoumarol 47 1 ‘Acetaminophen a7 1 ‘Acotaniide os 1 ‘Acetazolamie 74,01 3 Acetohydroxamic acid oa 1 sAcetylmethadol 86 i Acetysaiicylc acia 35 1 ‘Acyclovir 93 23 1 ‘Adriamycin 82 1 ‘Ajamaline 82 1 Albuterol 103 93 8 Alclofenac 43 1 Alfertai 65 1 ‘Alobarbital 78 1 ‘Alopuring| oa 14 ‘Alphaprogine a7 1 ‘Alprenoal 97. 18 ‘Alretamine 103 1 ‘Amantadine 90 1 ‘Amiginocilin 34 39 1 ‘mitre ar 1 ‘Aminoactine | 100 1 rAminobenzoic acid 49 25 1 ‘Aminocaproic acid 44 108 1 ‘Aminohippurc acid 38. 1 ‘Amninopterin 55 1 ‘Aminopyrine 50 1 p-Aminosalicylic acid 26 18 1 ‘Aminothiagiazole 32 1 ‘Amiodarone 66 1 ‘Amiteiptyine 94 5 ‘amobarbital 8 1 ‘Amoxapine 76 14 ‘Amoxcilia 24 96 Amphetamine 100 1 “Amphtericin 8 85 100 1 “Ampicitin 25 72 16 ‘nilercine 37,78 1 ‘Antazoiine 25.101 1 Antipying 15 1 ‘Apomorphine 89 70 1 ‘Aprobarbital 80 i ‘Ascorbic acid 42,118 1 ‘Atenolol 96 6 Atropine 98 1 Azatedine 93 1 ‘Azathioprine 80 8 Atoelin 28 1 ‘Aatrenam 07.29 39 1 Bacampictiin 68 1 Baclefen 54 95 1 Barbial 79 1 Bencrofumethiazide 85 5 (Continsed)APPENDIX A, 1344 Table A1. Continued Drugs: HA HB" Reference Benzocaine 25 1 Benzphetamine 66 1 Banzquinamide 59 1 Benztropine 100 1 Batanistine 35,98 1 Betaprodine 87, 1 Bethanidine 106 1 Bromazepam 110 29 1 Bromacrintine* 98 1 Bromodiphonydramine 43 7 ‘Bromphenitamine 36.98 1 Brucine 82.25 1 Butualo! 89 1 Bumotanide 52,100 1 Bunoiol 93 1 Bupivacaine an 1 Bupropion 10 8 Burimamige 75 1 Butabarbital 79 1 Butacaine 90 1 autaclamol 72 1 Butamben 54 1 Butorphanol a6 1 Bulylated hydroxytoluene 78 1 Bulyiparaben 85 3 Catone >140 06 1 Campiotecin 108 1 Captoprit 37,98 4 Carbachol 48 1 Carbenicilin ar 1 Carbenoxolone 67.74 i Carbinoxamine aa 1 Carisoprodol 42 4 Carpindolol Be 1 Gefactor 18 72. 8 Getamandole a7 8 Cetazolin 24 1 Cefoperazone 26 4 Cofotaxime 34 4 Gotoxtin 22 10 Ceftazidime 18.27 4a " Cetizoxime 27 2a 4 Ceftiaxone 32,44 32 1 Cefuroxime 4 Cophacetilo 3 Cophalexin® 32 1 LCephalogiyein 46 7 1 Gephaloridine 34 1 Cephalothin 25 1 Cophapirin 4 Cephradine 4 CChenocio! 43 14 Chior hydrate 100 16 Chlorambucil 58 4 Chlorcyetizine 21,82 1 Chlordiazepoxide 48 1 Chlommexiaine 108 1 CChlorocreso! 96 1 CChleroguin 81,99 1 @-Chiorotheophyling 82 1 Chlorohiazide 68,95 1 Chiorpheniramine 90 1 Ghlorpnentermine 96 1 ApePENDIXA Drugs Chlorpromazine Chorproparnide Chlorprotixene (Chloretracycine® Chlothalidane (Chlorzoxazone Cimetidine Ginchenine CCiprofioxacin Cindamyoin Clofirate Clonazepam Clonidine CCloperthixat Clotimazole Gloxacitin Clozapine Cocaine Codeine Calchicine Cromoiyn CGyanocobalamin Gyclactin Cyclazocine yelzine Cyelobarbita Gyclobenzapine yclopentamine Gyclopentoiato Cycloserine Gyctotiazice® Cyproheptadine Cytarabine Dacarbazine Dantiolone Dapsone Daunorubicin Debrisoquin Dehydrochatc acid Domectocyeine Demoxepam Desarpiine® Desipramine Dexroamphetamine Dextrobrompheniramine Dexrochiorpheniramine Dexrofentiuramine Dextroindoprofen Dexromethorphan Dextromoramide Diacetyimorphie (heroin) Diatizic acid Diazepam Diazoxide Dibenzepin Dibucaine Dichiorphenamide Diclofenac Dicloxactlin Dicouraro Dicyclomine Diathazine Diathytcarbamazepine Ditrisal Dinyeroergocriptine HA 49 33,74 98 83 60 35 105 28 14,19 a7 86 91,105 78 52 33,72 46 a4 85 74,86 45 28 44,80 30 BK, Values HE" 93 88,76 61,76 13.28 a4 119 a4 45,106 67 104 99 93 92 a4 83 79 78 34 83 83 99 aa ay 69 1345APPENDIX Table A1. Continued PK, Values Drugs HA He" elerence Diyaroergocrsine 69 1 Dinydroergotamine 69 1 Dityarostreptomycin 78 1 Dilevoio 95 1 Ditiazem 17 1 Dimethacione 61 1 Dimethisoguin 63 1 Dinoprost® 49 1 Dinoprostone 46 1 Diperedon a4 " Diphenhydramine at 1 Diphenoxyiate 7A 1 Diphenylpyraline 89 1 Dipioanone 85 1 Dipyridamoto 64 1 Disopyramice 102 a4 1 Dobutamine 95 14 Dopamine 108 39 1 Doxepin 90 1 Doxorubicin 82,102 1 Doxycycine 34,77 95 1 Doxylamine 44,92 1 Droperio! 78 1 Emetine 82,74 1 Enalapril 30 55 1 Enalapeat 23,94 80 1 Ephedrine 96 1 Epinephrine 89 100 1 Ergometrine 73 1 Ergonovine 6B 1 Exgotamnine 64 1 Exythromycin 88 1 Estrone’ 108 13 Ethacrynic acid 3.50 1 Ethambuto! 63,95 1 Ethoheptazine 85 1 Ethopropazine 96 1 Ethosuximide 95 1 Ethoxazolamide at 1 thy biscoumacetato 75 1 Ethyimorphine 82 1 Ethyinorepinephrine 84 1 Elocaine 79 1 Eilleprine 90 102 1 Etomidate 42 1 Eugenat 98 1 Fenclofenac 45 1 Fenfturarine on 1 Fenotero!, 100 86 1 Fonprofen 45 1 Fentanyl a4 “ Foxuridine 74 1 Flubiprofen 43 1 Flucloxacilia| ar 1 Flucyeosine 107 29 1 Fifenamic acid 39 10 Fiurizole 107 1 Funitrezepam 18 1 Fluorouracil 80.130 1 Flupenthixo! 78 1 Fluphenazine enanthate 35,82 1 Fluphenazine 39.81 1 Flupromazine 32 1 Flurazepam 82 19 1 :ENDIX A Drugs HA HB Reerence Furosemide 39 1 Fusidie acig 54 1 ‘Gentamicin® 82 1 Gilibenclamide 53 8 Glipizide 59 1 Glutetimide 92 1 Giyburide 53 1 Gheyclamine 55 1 Guanathigine 83,119 1 Guanoxan 23 1 Haloperigot 83 1 Hexetidine 83 2 Hexobarbital 82 1 Hexyicaine oa 1 Hexyresorcinol 95 1 Hippuric acid 36 1 Histamine 59,98 1 Homatropine 97 1 Hycanthone 34 1 Hydralazine 05,71 1 Hydrochiorotiazide 70,92 1 Hydrocodone 89 1 Hydrocortisone sodium Ba 1 ‘succinale Hydrofumethiazide 89, 107 1 Hydromorphone a2 1 Hydroquinone 100,120 1 Hycrosyamphetamine 93 1 Hycroxyzine 20,71 1 Hyoscyamine 97 3 tbuproten 52 1 Idoxuridine 83 1 Imipramine 95 i Indapamide 88 5 Indomethacin 45 1 Indoproton| 58 1 Indoramin 7 1 locetamic acia® 410043 4 logipamice 35 1 lodoguinot 80 1 lopanoic acid 48 4 tprindola 82 1 Ipronidazole ar 1 Isocarboxazid 104 1 Isoniazid 20,35, 108 1 Isoproterenol 104,121 86 1 Isoxsuprine 98 80 1 Kanamyein 72 1 Ketamine 75 att Ketobemidone 87 1 Ketoconazole 29,65 14 Ketoprofen" 48 19 Labetall ar 74 1 Leucovorin 31,84, 104 1 Levalorphan tartrate 48 69 1 ‘Levobunol 92 1 Lovodopa 23,97, 194 a7 1 Levomethorahan 83 1 Levomoramide 70 1 Levonocdetin 98 a6 1 LLevopropoxyphene 63 1 Levorphano! 92 1 Levothyroxine 22.67 10.1 1 Lidocaine 78 1 Lincomyein 75 1 (Continued)1348 Table A1. Continued APPENDIX, Drugs Lotryronine | Usinopri Loperamide Lorazepam Loxapine Lysergide Maprotiine Mazindo! Mecamylamine Mechiorethamine Mecizine Meciofenamic acs Medazepam Mofenarnic acis Mepazine Meperidine Mephentermine Mephoberbita Mepindotol Mepivacaine Mercaptornerin Mercaptopurine Mesalamine Mesna Metaproterenol Metaramin! Methacycine Methadone Metiamphetarine Methapyrilene Methaqualone Metharbital Methazolamide Methaliazine Methenarine Methciin Mathonexta Methotrexate Methotimeprazine Methoxamine Methoxyphenamine Methyclothiazide Methyl nicotinate Methyl paraben Methyl salicylate Methyldopa’ Methylergonovine Methyiphenicate ‘Metyithiourac ‘Methypryton Methyseraide Metoclopramide Metolazone Metopon Metoprolol Metronidazole Metyrosine Mextetine Mezlocilin Miconazole Midazolam Minocyeciine Minox PK, Values HA 84 17,33, 114 18 4 84 99 23, 10.4, 126 a2 120 97 ar 28,50,78f | APPENDIX A, Drugs HA 8° ee eee eee ee eee eee eee Matornycin 109 Molindone 89 Morphine a9 80 Moralactam 25,77, 102 Nabilone® 135 ado! 94 Natta ar Nafbuphine 100 a7 Nadie acid 80 Nalorphine 18 Naloxone 73 Naphazoine 109 Naproxen 42 Natarycio 46 aa Neostigmine 120 Nacin 20 48 Neotnamige 05.94 Nesting 31,80 Nikethamide 35 Nitrazopam 108 32 Nitoturanion 7A Norcodeine 87 Nordetrin 2 85 Notepinaphrine 98,120 86 Norfenephrine 87 Noxmorphine 98 Noctiptyine 97 Noscapine 62 Novobiocin 43.01 Nystatin 89 6A Octopamine 95 89 Orphenadrine 34 Oxacilin 27 Oxazopam 16 18 Oxprenola 95 ‘Oxybutynin 79. ‘Oxycodone 83 Oxymorphone 93 85 xyphenbutazono 47 Oxypurine! 77 Oxytetracycine® 33,73 9a Pamaquine 13,35, 100 Papaverine 64 Pargyiine 63. Pemotine 105 Penbutolor® 93 Penicilamine 18,105 79 Penicilia G 28 Pericilia V 27 Pentamicine 4 Pentazocine 100 85 Pentobarbita a4 Pontoxipryline 03 Perphenazine 37,78 Phanacetin 22 Phonazocine 85 Pheneyclcine 85 Phendimetrazine 78 Phenethicitin 28 Phentormin 27.18 Phenindamine 83 Phonindione 4a Phoniramine 42,03 Phenmetrazine 85 Phenobarbital, 1 (Continued)1380 APPENDIXA Table A1. Continued PA, Values Drugs HA HB" Retrence Phenoiphinalein 97 1 Phenotsufonphitalin 84 1 Phenothiazine 25 1 Phenoxybenzamine 44 4 Phenoxypropazine 69 1 Phentermine | 10.1 1 Phentolamine 17 1 Phenylbutazone 45 1 Phenylephrine 104 88 1 Phenyipropanolamine 94 1 Phonyitlovamine aa 1 Phenyramido! 59 1 Phenytoin a3 1 Physostignine 20,82 1 Pilocarpine 46,74 1 Pimoaide 73,868 1 Piadoot as 1 Piperazine 56,98 1 Pipradrol 97 1 Piruterol 30, 7.0,103 1 Phoxicam 46 1 Pivampiclin 70 1 Polyrnyain 89 1 Polytiazide 98 i Practolol 95 1 Praldoxime 73 1 Pramoxine 2 1 Prazepam 20 1 Prazosin 65 1 Pronaltero! 100 95 1 Prlocaine 73 1 Probenecid 34 1 Procainamide 92 1 Procaine a8 1 Procarbazine 68 1 Prochlorperazine 37,84 1 Promazine 9a 1 Promethazine a4 1 Proparacaine 32 " Propiomazine 94 1 Propoxyoane a6 1 Propoxyphene 63 1 . Propranoiot 95 1 Propylhexedrine 104 1 Propylthiouact 78 1 Psoudoephediine 95 1 Pyrathiazine 89 1 Pyrazinamide 05 1 Pyridoxine 896 50 1 Pyrilamine 40,89 1 Pyrimethamine 73 1 Pyrrobutamine 38 1 uinacrine 82,102 1 Quinethazone 93,107 1 Quinine 42,79 1 Quinine 42.85 1 Ranitidine 23.82 4 Feseinnamine 6a 4 Reserpine 66 1 Ritampin 7. 79 1 Fimaterot 103 87 1 Fitodrine 90 1 Roltetracyctine 74 1APPENOKXA 1351 PK, Values Drugs HA He" Fotoxamine 84 1 Saccharin 16 1 Saloylamride 82 3 Salicyic acid 30,194 1 Salsalate 35.98 12 Scopolamine 78 1 Secobarbital 79,126 1 Serotonin gs 49,031 1 Sotalo! a5 98 1 Sparieine 48,120 1 Spiperone 33.91 1 Streptozocin 13 4 Styehnine 23,80 1 ‘Succinylsulathiazole 45 1 Sutertani 80 4 Sulfacetamide 54 18 1 Sultediazine 65 20 1 Sulfedimethoxino 67 20 1 Sulfaguanidine 14 28 1 Sulfamerazine 7A 23 1 Sulfamethazine 74 24 1 Sulfamethizole 65 20 1 Sulfamethoxazole 56 1 Sulfapnenazole 65. 19 1 Sultapyricine 843 26 1 Sulfasalazine 24,07,118 1 Sulathiazole m4 24 1 ‘Sulinpyrazone 23 1 Sulsoxazole 50 1 Sulindac 45 1 Suliride oa 1 Sulthiare 100 1 P-Synephiine 102 9 1 Talbutal 78 1 Tamoxifen 89 4 Terazepam 18 1 Tereutaine 104,112 88 1 Tetracaine 84 1 Tetracycine 33.7.7 97 1 Tetrahydrocannabinol (THC) 108 2 Tetrahycrozotine 105 1 Thonyidiamine 39,09 1 Theobromine 10.1 onl 1 ‘Theophyline 86 35 1 ‘Thiarbendazole ay 4 Thiamine 48,90 1 Thiarylal 75 1 ‘Thioguanine 82 4 ‘Thiopental 75 1 ‘Thiopropazate 32,72 1 Thierdazine as 1 ‘Thithixene 77.79 1 Thiowraci 75 1 ‘Thonzylamine 22,90 1 Thyroxine 22,67 40.1 1 Tearcilin 26.34 1 Ticrynaten ar 1 Timalot as 1 Timoprazole 31,08 1 Totigine 68 1 Tiprofanic acid 300 1 Tobramycin 67,83,09 2 Tocsinide 15 1 Tolamolol 73 8 Totazamige 34 57 1 (Contowed)1382 APPENDIX A, Table A.1. Continued PA Values: Drugs. HA He" Reference Tolazoline 103 1 Tolbutamide 54 1 Tometin 35 1 Tremaine 107 1 Tranyleypromine 82 1 Trazodone 67 1 Tiamterene 62 1 Tichlormethiazide a6 1 “Tlluperazine 39,81 13 Tiilypromazine 92 1 Timeprazine 90 1 Timethobenzamige 83 1 “Timethopyin 66 3 Timipraming 80 14 Tipelernarine 42,87 1 Tiron 65 1 Troleandomycin 66 1 ‘Trometharine 81 1 “Topicamide 53. 1 Tuaminoheptane 105 1 ‘Tubocurarine 81,01 1 Tyramino 109 93 1 Valproic acis 48 1a ‘Verapamil 89 1 Vidarabine 35,125 1 Viloxazine a4 1 Vinbarbital 80 1 Vinbiastine 54,74 1 Vincristine | 50,74 1 Vindesine 60,77 1 Warfarin 54 1 Xyiomelazoline 102 1 Zmeldine 38.074 1 ‘Miscoltaneous organic acids and bases alc acid 48 Alyarine 107 6.Aminopeniilanic acid 23 49 ‘Ammonia 93 aniline 46 Benzoic acid 42 Bonzyl alcohol 480 Berzyiamine | 93 Butyrc acid 48 Carbonic acie 64,104 Give acid 31,4854 Diethanolamine 89 Diethyiamine 110 Dimethyiamine 107 ‘p-Dimathyiaminobenzoic acid 5A Ethanol 186 Enhanolarrine 95 Enyiamine 107 Ethyionediamine 72,100 Fumaric aia 30,44 Gluconie acid 36 Giucuronic acid 32 Guanidine 136 \midazole 70 Isopropyiarrine 108 Lactic acid 39 Maleic acts 19YOKA APPENDIX 1353 PA, Values Drugs. HA He" Roterence Mandelic acid 34 Monochloreacetic acis 29 N-propyiamine 108 Niremethane 110 Phenol 99 Phiatic acia 29 Resorcinol 92,113 Sorbie acia 48 Succinimide 96 Tartar acid 30,44 p-ToWidine 53 Tichloroacotic acia 09 Tiethanolamine 78 “Thethyiamine 107 Tropic acid aa Tropine 104 Uric acid 54 ‘Deternined in rainy cotloscvewater (8:2 wh inte) "Determined in G5 simethyermami, Determined in 2519 20% ehana. Determined in 40% mean. ‘Prosiaandn Fa. 'Spectophotomatic cetrninaton. {The bk, vals of ho fou opal somes ar. for wo lsrers and 4.25 for wo somes. determined in rshanotwato: (1 mice) ‘Determine in cimotyomramicavatr (11 mtr) 'Determinedin 5% diratyermarnide General References Aber A, Sexeant EP. The Determination of lonzation Constants of Ack and Buses A Laboratory Manual rd Ea. Now York, Chapman and Hall 1088 "ory Kd. Anal Proies of Dros Suances New eck Acad Pre, "3 Hansch ©, Samer PO, Tylor JB, eds. Comprehensive Medicinal Chemiy, Vol 6 Pergamon Press: Oxo, 190 (O'Nat A, Heckelman PE, Koch CB, eta The Merck Index. 4th Ed, Raby, Merk and Co 3006, ‘erin DD, DempscyB, Sexjeant EP pa Prediction for Organi Acs and Bae. ‘New Yor: Chapnan a Hal 18 Sexeant EP, Dempocy B lnization Constants of Organic Aci in Aqueous "Sludon, TUPAC Chemical Data Series No. 28, Oxford, UK: Pergainon Press, 1079. ‘Sinko F Man's Pyscal Pharmacy and Pharmaceutical Sciences Sih Ed Bal moc: Lippincot Walla & Wiking, 205.1354 Table B.1.__pH Values for Tissue Fluids Fug pH ‘Aqueous humor 72 Blood, arterial 74 Blood, venous 74 Blood, maternal umbilical 73 Corebrospinal hid 14 Colon Fasting 58 Fed 58 Duodenurnt Fasting 4486 Fed 52-62 Feces? 7146-88) leum® Fasting ass Fed 68-80 Intestine, micrsurtace 53 Lactimal uid (wars) 74 Mik, breast 79 Muscle, skelter 60 ‘Nasal secretions 60 Prostate uid 65. salva 64 ‘Semen 72 Stomach* Fasting 1424 Fed a7 ‘Sweat 54 Urine 58 (65-70) ‘Vaginal secetons, prerienopause 45 ‘Vaginal scrotons, postmonopause 19 “Oressman JB, Amidon GL, Reps C eal Diseohontstng as & progres toa for oral drug absorption Pharm Ros 1996/15:1-22. ator ne seit omod tol. Hard stots end to be ore alkali, weer, formed tools are aia onde Iracelsrly on he a. Page nu de Ides gener 4 Resenic ‘tml stsacepe ‘Reina hes, sects Aecamine 325.95 ‘ecohexs pened cee Aeobiene feel ‘cairo ‘elon SSaEpom ‘endo ‘nour eobetft ‘iesenn ‘Nendronas =a featonca ‘Aopurna, ‘Amorpian ‘milace, 1 iter, inode ‘Amines aig Aainogiet