%PDF-1.4 % 12 0 obj <> endobj 66 0 obj <>stream /Artifact <>BDC q 1 i 0 841.89 595.276 -841.89 re 297.645 420.96 m W n .015015 841.89 595.29 -841.89 re W n 1 .1 0 .1 k /GS1 gs .015015 0 595.29 31.48 re f EMC /P <>BDC BT /TT4 1 Tf 46 0 0 46 36.6675 582.3612 Tm 1 .89 0 0 k 0 Tc 0 Tw (Predicting Drug )Tj ET EMC /P <>BDC BT 46 0 0 46 36.6675 538.1613 Tm (Absorption in Patients)Tj ET EMC /P <>BDC BT 46 0 0 46 527.3491 538.1613 Tm ( )Tj ET EMC /P <>BDC BT 46 0 0 46 36.6675 493.9614 Tm (with a Short Bowel)Tj ET EMC /Figure <>BDC Q q 1 i 480.855 791.282 99.247 -87.11 re 448.13 493.961 m W* n 0 841.89 595.276 -841.89 re 297.645 420.96 m W n .015015 841.89 595.29 -841.89 re W n /GS1 gs q 90.236 0 0 87.548 488.367 703.974 cm /Im1 Do Q EMC /Artifact <>BDC Q q 1 i 0 841.89 595.276 -841.89 re 297.645 420.96 m W n .015015 841.89 595.29 -841.89 re W n 1 .89 0 0 k /GS1 gs q 1 0 0 1 298.526 464.902 cm 0 0 m 257.014 0 l 258.58 0 259.849 -1.2693 259.849 -2.835 c 259.849 -75.548 l 259.849 -77.114 258.58 -78.383 257.014 -78.383 c -257.014 -78.383 l -258.58 -78.383 -259.849 -77.114 -259.849 -75.548 c -259.849 -2.835 l -259.849 -1.2693 -258.58 0 -257.014 0 c h f* Q EMC /P <>BDC BT /TT2 1 Tf 11 0 0 11 58.6931 438.4203 Tm 0 0 0 0 k -.0003 Tc -.0414 Tw [(The absorption of drugs in patients with a short bowel \(SB\) can be hard to predict. It may be af)18(fected)]TJ ET EMC /P <>BDC BT 11 0 0 11 538.0809 438.4203 Tm 0 Tc 0 Tw ( )Tj ET EMC /P <>BDC BT 11 0 0 11 58.6931 422.4203 Tm .0074 Tw (by the remaining length and type of functioning gut, gastric emptying and small bowel transit rates,)Tj ET EMC /P <>BDC BT 11 0 0 11 538.0778 422.4203 Tm 0 Tw ( )Tj ET EMC /P <>BDC BT 11 0 0 11 58.6931 406.4203 Tm (gastric secretion, bowel perfusion and the physicochemical properties of the drug. )Tj ET EMC /P <>BDC BT 11 0 0 11 459.1888 406.4203 Tm ( )Tj ET EMC /P <>BDC BT /TT4 1 Tf 12 0 0 12 39.993 370.5117 Tm 1 .89 0 0 k (Key points)Tj ET EMC /P <>BDC BT /TT2 1 Tf 8 0 0 8 101.3348 370.5117 Tm 0 0 0 .8 k ( )Tj ET EMC /P <>BDC BT 8 0 0 8 39.993 355.6769 Tm (1.)Tj ET EMC /P <>BDC BT 8 0 0 8 49.109 355.6769 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 51.3317 355.6769 Tm [(A)55.2( knowledge of how much functioning small and large bowel )]TJ ET EMC /P <>BDC BT 8 0 0 8 49.109 343.6769 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 51.3317 343.6769 Tm (remains helps predict absorption. )Tj ET EMC /P <>BDC BT 8 0 0 8 171.3942 343.6769 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 39.993 326.0078 Tm (2.)Tj ET EMC /P <>BDC BT 8 0 0 8 49.109 326.0078 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 51.3317 326.0078 Tm (The time to the blood maximum drug concentration \(Tmax\) )Tj ET EMC /P <>BDC BT 8 0 0 8 49.109 314.0078 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 51.3317 314.0078 Tm (and oral bioavailability help predict absorption. )Tj ET EMC /P <>BDC BT 8 0 0 8 217.6559 314.0078 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 39.993 296.3385 Tm (3.)Tj ET EMC /P <>BDC BT 8 0 0 8 49.109 296.3385 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 51.3317 296.3385 Tm (The biopharmaceutical classification system \(BCS\) is based upon )Tj ET EMC /P <>BDC BT 8 0 0 8 49.109 284.3385 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 51.3317 284.3385 Tm -.01 Tc (drug solubility and permeability and helps predict the drug absorption.)Tj ET EMC /P <>BDC BT 8 0 0 8 292.0259 284.3385 Tm 0 Tc ( )Tj ET EMC /P <>BDC BT 8 0 0 8 39.993 266.6692 Tm (4.)Tj ET EMC /P <>BDC BT 8 0 0 8 49.109 266.6692 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 51.3317 266.6692 Tm (Lipid soluble drugs need a long length of bowel to be absorbed )Tj ET EMC /P <>BDC BT 8 0 0 8 49.109 254.6692 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 51.3317 254.6692 Tm (so are likely to be poorly absorbed in patients with a SB.)Tj ET EMC /P <>BDC BT 8 0 0 8 250.109 254.6692 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 39.993 236.9999 Tm (5.)Tj ET EMC /P <>BDC BT 8 0 0 8 49.109 236.9999 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 51.3317 236.9999 Tm [(Caution should be used with drugs that are ef)18.1(ficacious within )]TJ ET EMC /P <>BDC BT 8 0 0 8 49.109 224.9999 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 51.3317 224.9999 Tm (a narrow therapeutic range.)Tj ET EMC /P <>BDC BT 8 0 0 8 149.1676 224.9999 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 39.993 207.3306 Tm (6.)Tj ET EMC /P <>BDC BT 8 0 0 8 49.109 207.3306 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 51.3317 207.3306 Tm -.005 Tc (Due to malabsorption, a drug that readily forms a solution may )Tj ET EMC /P <>BDC BT 8 0 0 8 49.149 195.3306 Tm 0 Tc ( )Tj ET EMC /P <>BDC BT 8 0 0 8 51.3317 195.3306 Tm -.005 Tc [(be given in higher than normal doses. However)55.2(, a formulation )]TJ ET EMC /P <>BDC BT 8 0 0 8 49.149 183.3306 Tm 0 Tc ( )Tj ET EMC /P <>BDC BT 8 0 0 8 51.3317 183.3306 Tm -.005 Tc (that bypasses the gastrointestinal tract \(GIT\) may be better )Tj ET EMC /P <>BDC BT 8 0 0 8 49.149 171.3306 Tm 0 Tc ( )Tj ET EMC /P <>BDC BT 8 0 0 8 51.3317 171.3306 Tm -.005 Tc (\(e.g., by injection or infusion, topical, buccal or rectal application\).)Tj ET EMC /P <>BDC BT 8 0 0 8 279.6837 171.3306 Tm 0 Tc ( )Tj ET EMC /P <>BDC BT 8 0 0 8 39.993 153.6613 Tm (7.)Tj ET EMC /P <>BDC BT 8 0 0 8 49.109 153.6613 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 51.3317 153.6613 Tm (Prolonged released drug formulations should be avoided in )Tj ET EMC /P <>BDC BT 8 0 0 8 49.109 141.6613 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 51.3317 141.6613 Tm (patients with a SB.)Tj ET EMC /P <>BDC BT 8 0 0 8 117.5895 141.6613 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 39.993 123.992 Tm (8.)Tj ET EMC /P <>BDC BT 8 0 0 8 49.109 123.992 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 51.3317 123.992 Tm [(Careful monitoring of drug blood levels or of an ef)18.1(fect \(e.g., INR )]TJ ET EMC /P <>BDC BT 8 0 0 8 49.109 111.992 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 51.3317 111.992 Tm (for warfarin\) may be needed to achieve the desired clinical outcome)Tj ET EMC /P <>BDC BT 8 0 0 8 291.0153 111.992 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 49.109 99.992 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 51.3317 99.992 Tm (and avoid an adverse reaction. )Tj ET EMC /P <>BDC BT 8 0 0 8 165.1832 99.992 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 39.993 82.3227 Tm (9.)Tj ET EMC /P <>BDC BT 8 0 0 8 49.109 82.3227 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 51.3317 82.3227 Tm (Absorption may improve over time due to intestinal adaptation )Tj ET EMC /P <>BDC BT 8 0 0 8 49.109 70.3227 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 51.3317 70.3227 Tm (\(especially in patients with a colon in continuity\) or to drugs that )Tj ET EMC /P <>BDC BT 8 0 0 8 49.109 58.3227 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 51.3317 58.3227 Tm (slow gut transit.)Tj ET EMC /P <>BDC BT /TT4 1 Tf 12 0 0 12 106.9098 58.3227 Tm 1 .89 0 0 k ( )Tj ET EMC /P <>BDC BT 12 0 0 12 305.1843 370.5117 Tm (Explanations)Tj ET EMC /P <>BDC BT /TT2 1 Tf 8 0 0 8 379.8679 370.5117 Tm 0 0 0 .8 k ( )Tj ET EMC /P <>BDC BT 8 0 0 8 305.1843 355.377 Tm -.005 Tc (1.)Tj ET EMC /P <>BDC BT /TT4 1 Tf 8 0 0 8 314.3402 355.377 Tm 0 Tc ( )Tj ET EMC /P <>BDC BT /TT2 1 Tf 8 0 0 8 316.5228 355.377 Tm -.005 Tc [(A)55.2( patient with a duodenostomy is unlikely to absorb much of any oral)]TJ ET EMC /P <>BDC BT 8 0 0 8 556.6089 355.377 Tm 0 Tc ( )Tj ET EMC /P <>BDC BT 8 0 0 8 314.3402 343.0771 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 316.5228 343.0771 Tm -.005 Tc (preparation, while a patient with a metre of small bowel in continuity )Tj ET EMC /P <>BDC BT 8 0 0 8 314.3402 330.7771 Tm 0 Tc ( )Tj ET EMC /P <>BDC BT 8 0 0 8 316.5228 330.7771 Tm -.005 Tc (with more than half their colon may absorb most of a medication. )Tj ET EMC /P <>BDC BT 8 0 0 8 314.3402 318.4771 Tm 0 Tc ( )Tj ET EMC /P <>BDC BT 8 0 0 8 316.5228 318.4771 Tm -.005 Tc (The majority of drugs given orally are absorbed from the jejunum )Tj ET EMC /P <>BDC BT 8 0 0 8 314.4202 306.1769 Tm 0 Tc ( )Tj ET EMC /P <>BDC BT 8 0 0 8 316.5228 306.1769 Tm -.015 Tc [(due to its large surface area. )18.1(There needs to be a good understanding)]TJ ET EMC /P <>BDC BT 8 0 0 8 556.2667 306.1769 Tm 0 Tc ( )Tj ET EMC /P <>BDC BT 8 0 0 8 314.3402 293.877 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 316.5228 293.877 Tm -.005 Tc [(of the patient)18.1(s gastrointestinal in-circuit anatomy \(and out of circuit )]TJ ET EMC /P <>BDC BT 8 0 0 8 314.3402 281.5771 Tm 0 Tc ( )Tj ET EMC /P <>BDC BT 8 0 0 8 316.5228 281.5771 Tm -.005 Tc (anatomy if a chyme reinfusion is being considered\). )Tj ET EMC /P <>BDC BT 8 0 0 8 498.983 281.5771 Tm 0 Tc ( )Tj ET EMC /P <>BDC BT 8 0 0 8 305.1843 263.8078 Tm (2.)Tj ET EMC /P <>BDC BT /TT4 1 Tf 8 0 0 8 314.3002 263.8078 Tm ( )Tj ET EMC /P <>BDC BT /TT2 1 Tf 8 0 0 8 316.5228 263.8078 Tm (The highest blood concentration \(Cmax\) and the time that the )Tj ET EMC /P <>BDC BT 8 0 0 8 314.3002 251.7077 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 316.5228 251.7077 Tm (maximum concentration is reached \(Tmax\) are dependent on )Tj ET EMC /P <>BDC BT 8 0 0 8 314.3002 239.6077 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 316.5228 239.6077 Tm [(the rate at which the drug enters and is removed from the body)74.2(. )]TJ ET EMC /P <>BDC BT 8 0 0 8 314.3002 227.5077 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 316.5228 227.5077 Tm (Drugs that reach their Cmax quickly \(less than two hours\) tend to )Tj ET EMC /P <>BDC BT 8 0 0 8 314.3002 215.4077 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 316.5228 215.4077 Tm (be absorbed higher in the gastro-intestinal tract so are more likely )Tj ET EMC /P <>BDC BT 8 0 0 8 314.3002 203.3077 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 316.5228 203.3077 Tm [(to be absorbed in patients with SB \(e.g. fluconazole )18.1(Tmax 0.5 -1.5 )]TJ ET EMC /P <>BDC BT 8 0 0 8 314.3002 191.2077 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 316.5228 191.2077 Tm [(hours\) while those that are absorbed slowly \(e.g. amlodipine )18.1(Tmax )]TJ ET EMC /P <>BDC BT 8 0 0 8 314.3002 179.1077 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 316.5228 179.1077 Tm (6-12 hours\) are not. Oral bioavailability is the amount of active drug )Tj ET EMC /P <>BDC BT 8 0 0 8 314.3002 167.0077 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 316.5228 167.0077 Tm (that reaches the systemic circulation after oral administration. )Tj ET EMC /P <>BDC BT 8 0 0 8 314.3002 154.9077 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 316.5228 154.9077 Tm (It ranges from 1 \(100% of the drug reaches the systemic circulation\))Tj ET EMC /P <>BDC BT 8 0 0 8 556.6322 154.9077 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 314.3002 142.8077 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 316.5228 142.8077 Tm (to 0, \(none of the drug reaches the systemic circulation\). Oral )Tj ET EMC /P <>BDC BT 8 0 0 8 314.3002 130.7076 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 316.5228 130.7076 Tm (bioavailability of medicines can also change when switching from )Tj ET EMC /P <>BDC BT 8 0 0 8 314.3002 118.6077 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 316.5228 118.6077 Tm [(one formulation to another)55.2(. For example, digoxin tablets and liquid )]TJ ET EMC /P <>BDC BT 8 0 0 8 314.3002 106.5077 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 316.5228 106.5077 Tm (are not bioequivalent therefore a dose adjustment may be required. )Tj ET EMC /P <>BDC BT 8 0 0 8 314.3002 94.4076 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 316.5228 94.4076 Tm (The most quickly absorbed drug in each class \(e.g., lacipine in )Tj ET EMC /P <>BDC BT 8 0 0 8 314.3002 82.3077 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 316.5228 82.3077 Tm [(preference to amlodipine\) should be used. )18.1(The )18.1(Tmax, Cmax and )]TJ ET EMC /P <>BDC BT 8 0 0 8 314.3002 70.2076 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 316.5228 70.2076 Tm (oral bioavailability \(in normal subjects\) can be found in the )Tj ET EMC /P <>BDC BT 8 0 0 8 314.3002 58.1076 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 316.5228 58.1076 Tm [(manufacture)18.1(s information.)]TJ ET EMC /P <>BDC BT 8 0 0 8 410.644 58.1076 Tm ( )Tj ET EMC /P <>BDC BT /TT4 1 Tf 9 0 0 9 22.6772 814.1643 Tm 1 .15 0 0 k [(THE BRITISH INTESTINAL)18.1( F)55.2(AILURE )37.1(ALLIANCE \(BIF)55.2(A\) T)18.1(O)0(P)18.1( TIPS )37.1(ARTICLE SERIES)]TJ ET EMC /Artifact <>BDC 0 0 0 .6 k .015015 806.78 595.29 1.417 re f EMC /P <>BDC BT /TT2 1 Tf 8 0 0 8 22.6772 14.3571 Tm 0 0 0 0 k [(BIF)55.2(A)55.2( is a Specialist Interest Group of ϳԹ )]TJ ET EMC /P <>BDC BT /TT4 1 Tf 8 0 0 8 191.2006 14.3571 Tm [(www)37.1(.bapen.org.uk )]TJ ET EMC /P <>BDC BT /TT2 1 Tf 8 0 0 8 38.993 474.786 Tm 0 0 0 .8 k [(Uchu Meade, Richard Ng Kwet Shing, Jeremy Nightingale and the BIF)55.2(A)55.2( Committee)]TJ ET EMC /P <>BDC BT 6 0 0 6 510.4381 41.029 Tm (Continued over page...)Tj ET EMC /P <>BDC BT 8 0 0 8 536.7962 14.3585 Tm 0 0 0 0 k (May 2022)Tj ET EMC Q endstream endobj 67 0 obj <>/XObject<>/ExtGState<>>> endobj 74 0 obj <> endobj 160 0 obj <>stream /Figure <>BDC q 1 i -16 794.836 625.344 -936.03 re 297.645 420.96 m W* n 0 841.89 595.276 -841.89 re 297.645 420.96 m W n .015015 841.89 595.29 -841.89 re W n /GS2 gs q 702.114 106.142 -80.977 535.654 11.868 -89.181 cm /Im2 Do Q EMC /P <>BDC Q q 1 i 0 841.89 595.276 -841.89 re 297.645 420.96 m W n .015015 841.89 595.29 -841.89 re W n /GS1 gs BT /TT4 1 Tf 9 0 0 9 22.6772 814.1656 Tm 1 .15 0 0 k 0 Tc 0 Tw [(THE BRITISH INTESTINAL)18.1( F)55.2(AILURE )37.1(ALLIANCE \(BIF)55.2(A\) T)18.1(O)0(P)18.1( TIPS )37.1(ARTICLE SERIES)]TJ ET EMC /Artifact <>BDC 0 0 0 .6 k .015015 806.781 595.29 1.4171 re f EMC /Artifact <>BDC 1 .1 0 .1 k .015015 0 595.29 31.482 re f EMC /P <>BDC BT /TT2 1 Tf 8 0 0 8 22.6772 14.3583 Tm 0 0 0 0 k [(BIF)55.2(A)55.2( is a Specialist Interest Group of ϳԹ )]TJ ET EMC /P <>BDC BT /TT4 1 Tf 8 0 0 8 191.2007 14.3583 Tm [(www)37.1(.bapen.org.uk )]TJ ET EMC /Artifact <>BDC 0 0 0 .08 k 38 117.709 518.383 133.038 re f EMC /P <>BDC BT 9 0 0 9 55.4701 226.4822 Tm 1 .89 0 0 k (Suggested reading:)Tj ET EMC /P <>BDC BT /TT2 1 Tf 8 0 0 8 163.4701 226.4822 Tm 0 0 0 .8 k ( )Tj ET EMC /P <>BDC BT 8 0 0 8 55.4701 211.6476 Tm ()Tj ET EMC /P <>BDC BT 8 0 0 8 63.974 211.6476 Tm (Meade U et al. Drug absorption in short bowel. In Intestinal Failure Second edition \(in press by Springer\))Tj ET EMC /P <>BDC BT 8 0 0 8 432.6107 211.6476 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 55.4701 199.6476 Tm ()Tj ET EMC /P <>BDC BT 8 0 0 8 63.974 199.6476 Tm [(Hong WB, )18.1(T)110.8(an WK, Law LS, Ong DE, Lo EA. Changes of drug pharmacokinetics in patients with short bowel syndrome: a systematic )]TJ ET EMC /P <>BDC BT 8 0 0 8 63.974 187.6476 Tm [(review)55.2(. European Journal of Drug Metabolism and Pharmacokinetics. 2021 Jul;46\(4\):465-78.)]TJ ET EMC /P <>BDC BT 8 0 0 8 391.7083 187.6476 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 55.4701 175.6476 Tm ()Tj ET EMC /P <>BDC BT 8 0 0 8 63.974 175.6476 Tm [(W)37.1(ard N. )18.1(The impact of intestinal failure on oral drug absorption: a review)55.2(. Journal of Gastrointestinal Surgery)74.2(. 2010 Jun;14\(6\))]TJ 55.1211 0 TD (:1045-51.)Tj ET EMC /P <>BDC BT 8 0 0 8 538.7476 175.6476 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 55.4701 163.6476 Tm ()Tj ET EMC /P <>BDC BT 8 0 0 8 63.974 163.6476 Tm [(Papich MG, Martinez MN. )55.2(Applying biopharmaceutical classification system \(BCS\) criteria to predict oral absorption of drugs in )]TJ 56.0786 0 TD (dogs: )Tj ET EMC /P <>BDC BT 8 0 0 8 63.974 151.6476 Tm [(challenges and pitfalls. )18.1(The )55.2(AAPS journal. 2015 Jul;17\(4\):948-64.)]TJ ET EMC /P <>BDC BT 8 0 0 8 295.0873 151.6476 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 55.4701 139.6476 Tm ()Tj ET EMC /P <>BDC BT 8 0 0 8 63.974 139.6476 Tm [(BCS Database via http://www)55.2(.ddfint.org/)]TJ ET EMC /P <>BDC BT 8 0 0 8 206.267 139.6476 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 55.4701 127.6476 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 536.2428 14.3583 Tm 0 0 0 0 k (May 2022)Tj ET EMC /Artifact <>BDC 0 0 0 .08 k 50 502.399 241.04 217.588 re f EMC /P <>BDC BT 8 0 0 8 38.1139 776.0668 Tm 0 0 0 .8 k (3.)Tj ET EMC /P <>BDC BT /TT4 1 Tf 8 0 0 8 47.2299 776.0668 Tm ( )Tj ET EMC /P <>BDC BT /TT2 1 Tf 8 0 0 8 49.4525 776.0668 Tm (The BCS classifies drugs into four categories based upon solubility )Tj ET EMC /P <>BDC BT 8 0 0 8 47.2299 764.0668 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 49.4525 764.0668 Tm [(and permeability)74.2(. )55.2(A)55.2( drug with high solubility and high permeability )]TJ ET EMC /P <>BDC BT 8 0 0 8 47.2299 752.0668 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 49.4525 752.0668 Tm [(\(Class I\) is absorbed quickly and therefore achieves a fast )18.1(Tmax )]TJ ET EMC /P <>BDC BT 8 0 0 8 47.2299 740.0668 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 49.4525 740.0668 Tm (and a higher Cmax so there is likely to be some absorption even )Tj ET EMC /P <>BDC BT 8 0 0 8 47.2299 728.0668 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 49.4525 728.0668 Tm (in patients with a very short bowel \()Tj ET EMC /P <>BDC BT /TT4 1 Tf 8 0 0 8 174.3978 728.0668 Tm (see table)Tj ET EMC /P <>BDC BT /TT2 1 Tf 8 0 0 8 208.64 728.0668 Tm (\). )Tj ET EMC /P <>BDC BT 8 0 0 8 215.7494 728.0668 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 47.2299 705.5629 Tm ( )Tj ET EMC /P <>BDC BT /TT4 1 Tf 8 0 0 8 57.9564 705.5629 Tm [(T)74.2(able: Examples of drugs that have a Tmax of two hours )]TJ ET EMC /P <>BDC BT 8 0 0 8 47.2299 694.5629 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 57.9564 694.5629 Tm (or less and are BCS class I)Tj ET EMC /P <>BDC BT 8 0 0 8 160.2299 694.5629 Tm ( )Tj ET EMC /P <>BDC BT /TT2 1 Tf 8 0 0 8 47.2299 679.7283 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 57.9564 679.7283 Tm ( Paracetamol)Tj ET EMC /P <>BDC BT 8 0 0 8 107.89 679.7283 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 47.2299 667.7283 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 57.9564 667.7283 Tm ( Codeine phosphate)Tj ET EMC /P <>BDC BT 8 0 0 8 132.3705 667.7283 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 47.2299 655.7283 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 57.9564 655.7283 Tm ( Pregabalin)Tj ET EMC /P <>BDC BT 8 0 0 8 101.2299 655.7283 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 47.2299 643.7283 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 57.9564 643.7283 Tm ( Bisoprolol and Metoprolol )Tj ET EMC /P <>BDC BT 8 0 0 8 155.4759 643.7283 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 47.2299 631.7283 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 57.9564 631.7283 Tm ()Tj ET EMC /P <>BDC BT 8 0 0 8 63.6257 631.7283 Tm (Ramipril and Enalapril )Tj ET EMC /P <>BDC BT 8 0 0 8 144.1062 631.7283 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 47.2299 619.7282 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 57.9564 619.7282 Tm ( Levetiracetam)Tj ET EMC /P <>BDC BT 8 0 0 8 113.2259 619.7282 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 47.2299 607.7282 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 57.9564 607.7282 Tm ( Levofloxacin )Tj ET EMC /P <>BDC BT 8 0 0 8 109.6752 607.7282 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 47.2299 595.7282 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 57.9564 595.7282 Tm ( Metronidazole)Tj ET EMC /P <>BDC BT 8 0 0 8 113.2299 595.7282 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 47.2299 583.7282 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 57.9564 583.7282 Tm ( Lorazepam, zopiclone and midazolam)Tj ET EMC /P <>BDC BT 8 0 0 8 197.722 583.7282 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 47.2299 571.7282 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 57.9564 571.7282 Tm ()Tj ET EMC /P <>BDC BT 8 0 0 8 63.6257 571.7282 Tm (Mirtazepine)Tj ET EMC /P <>BDC BT 8 0 0 8 104.9773 571.7282 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 47.2299 559.7282 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 57.9564 559.7282 Tm [( V)55.2(enlafaxine)]TJ ET EMC /P <>BDC BT 8 0 0 8 104.3471 559.7282 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 47.2299 547.7282 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 57.9564 547.7282 Tm ( Cyclizine)Tj ET EMC /P <>BDC BT 8 0 0 8 94.9877 547.7282 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 47.2299 535.7282 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 57.9564 535.7282 Tm ( Ondansetron)Tj ET EMC /P <>BDC BT 8 0 0 8 109.2338 535.7282 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 47.2299 523.7282 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 57.9564 523.7282 Tm ( Lansoprazole*)Tj ET EMC /P <>BDC BT 8 0 0 8 114.1283 523.7282 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 47.2299 511.7282 Tm ( )Tj ET EMC /P <>BDC BT 5 0 0 5 57.9564 511.7283 Tm [(* Omeprazole )18.1(T)18.1( max is 0.5 hr but is BCS class II)]TJ ET EMC /P <>BDC BT /TT4 1 Tf 8 0 0 8 164.7558 514.7282 Tm ( )Tj ET EMC /P <>BDC BT /TT2 1 Tf 8 0 0 8 38.1139 502.7282 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 38.1139 485.059 Tm (4.)Tj ET EMC /P <>BDC BT /TT4 1 Tf 8 0 0 8 47.2299 485.059 Tm ( )Tj ET EMC /P <>BDC BT /TT2 1 Tf 8 0 0 8 49.4525 485.059 Tm (The un-ionized form of a drug is usually lipid soluble and can )Tj ET EMC /P <>BDC BT 8 0 0 8 47.2299 473.059 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 49.4525 473.059 Tm [(dif)18.1(fuse readily across the phospholipid cell membrane. However)55.2(, )]TJ ET EMC /P <>BDC BT 8 0 0 8 47.2299 461.059 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 49.4525 461.059 Tm (the proportion of ionised and un-ionised forms present at any )Tj ET EMC /P <>BDC BT 8 0 0 8 47.2299 449.059 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 49.4525 449.059 Tm (specific region is influenced by the pH of the solution and the pKa )Tj ET EMC /P <>BDC BT 8 0 0 8 47.2299 437.059 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 49.4525 437.059 Tm (of the drug. Drugs that are weak acids are better absorbed in )Tj ET EMC /P <>BDC BT 8 0 0 8 47.2299 425.059 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 49.4525 425.059 Tm (an acidic environment \(e.g., aspirin, penicillins and L-dopa\) and )Tj ET EMC /P <>BDC BT 8 0 0 8 47.2299 413.059 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 49.4525 413.059 Tm (weak bases in a more alkaline one \(e.g., pethidine\), where their )Tj ET EMC /P <>BDC BT 8 0 0 8 47.2299 401.059 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 49.4525 401.059 Tm (un-ionised forms predominate \(e.g., a drug with a pKa of 4 will )Tj ET EMC /P <>BDC BT 8 0 0 8 47.2299 389.059 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 49.4525 389.059 Tm (have increased solubility with increased pH and a drug with a )Tj ET EMC /P <>BDC BT 8 0 0 8 47.2299 377.059 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 49.4525 377.059 Tm (pKa of 7 will have increased solubility with lower pH\).)Tj ET EMC /P <>BDC BT 8 0 0 8 237.0931 377.059 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 38.1139 359.3897 Tm (5.)Tj ET EMC /P <>BDC BT /TT4 1 Tf 8 0 0 8 47.2299 359.3897 Tm ( )Tj ET EMC /P <>BDC BT /TT2 1 Tf 8 0 0 8 49.4525 359.3897 Tm (The therapeutic range is the concentration range in which the )Tj ET EMC /P <>BDC BT 8 0 0 8 47.2299 347.3897 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 49.4525 347.3897 Tm (drug is eliciting a therapeutic response. If the amount of drug )Tj ET EMC /P <>BDC BT 8 0 0 8 47.2299 335.3897 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 49.4525 335.3897 Tm (absorbed is too low then the concentration will fall below the )Tj ET EMC /P <>BDC BT 8 0 0 8 47.2299 323.3897 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 49.4525 323.3897 Tm (minimum needed to elicit the desired pharmaceutical response )Tj ET EMC /P <>BDC BT 8 0 0 8 47.2299 311.3897 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 49.4525 311.3897 Tm (and so result in treatment failure, if too high it may result in toxic )Tj ET EMC /P <>BDC BT 8 0 0 8 47.2299 299.3897 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 49.4525 299.3897 Tm [(adverse ef)18.1(fects. Drugs with a narrow therapeutic range include )]TJ ET EMC /P <>BDC BT 8 0 0 8 47.2299 287.3897 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 49.4525 287.3897 Tm (warfarin, digoxin, phenytoin and need to be used with caution as )Tj ET EMC /P <>BDC BT 8 0 0 8 47.2299 275.3897 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 49.4525 275.3897 Tm [(increasing their dose can suddenly result in toxic levels. )18.1(Their ef)18.1(fect )]TJ ET EMC /P <>BDC BT 8 0 0 8 47.2299 263.3897 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 49.4525 263.3897 Tm (\(e.g., INR for warfarin\) or drug levels will need to be monitored. )Tj ET EMC /P <>BDC BT 8 0 0 8 326.1139 263.3897 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 303.1747 776.0668 Tm (6.)Tj ET EMC /P <>BDC BT /TT4 1 Tf 8 0 0 8 312.2906 776.0668 Tm ( )Tj ET EMC /P <>BDC BT /TT2 1 Tf 8 0 0 8 314.5133 776.0668 Tm [(A)55.2( higher dose than recommended by the manufacturer)55.2(, of)18.1(f label/ )]TJ ET EMC /P <>BDC BT 8 0 0 8 312.2906 764.2668 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 314.5133 764.2668 Tm [(of)18.1(f licensed, is often needed to compensate for malabsorption of )]TJ ET EMC /P <>BDC BT 8 0 0 8 312.2906 752.4668 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 314.5133 752.4668 Tm (a drug in patients with a SB. Drugs with a wide therapeutic range )Tj ET EMC /P <>BDC BT 8 0 0 8 312.2906 740.6667 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 314.5133 740.6667 Tm (are most desirable for SB patients as these have a wider margin )Tj ET EMC /P <>BDC BT 8 0 0 8 312.2906 728.8668 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 314.5133 728.8668 Tm [(of safety)74.2(. )55.2(Adverse ef)18.1(fects of a drug can be obtained from its )]TJ ET EMC /P <>BDC BT 8 0 0 8 312.2906 717.0668 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 314.5133 717.0668 Tm (Summary of Product Characteristics \(SPC\).)Tj ET EMC /P <>BDC BT 8 0 0 8 468.775 717.0668 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 303.1747 699.5975 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 312.2906 699.5975 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 314.5133 699.5975 Tm [(When absorption is uncertain or if there are dif)18.1(ficulties in obtaining )]TJ ET EMC /P <>BDC BT 8 0 0 8 312.2906 687.7975 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 314.5133 687.7975 Tm (good oral absorption, alternative routes or methods need to be )Tj ET EMC /P <>BDC BT 8 0 0 8 312.2906 675.9974 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 314.5133 675.9974 Tm -.0181 Tw [(considered. These )-18.1(include:)]TJ ET EMC /P <>BDC BT 8 0 0 8 409.9821 675.9974 Tm 0 Tw ( )Tj ET EMC /P <>BDC BT 8 0 0 8 312.2906 664.1975 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 314.5133 664.1975 Tm ()Tj ET EMC /P <>BDC BT 8 0 0 8 320.1826 664.1975 Tm (intravenous intramuscular subcutaneous transdermal )Tj ET EMC /P <>BDC BT 8 0 0 8 525.5732 664.1975 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 312.2906 652.3975 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 314.5133 652.3975 Tm ()Tj ET EMC /P <>BDC BT 8 0 0 8 320.1826 652.3975 Tm (oro-mucosal rectal. )Tj ET EMC /P <>BDC BT 8 0 0 8 395.4521 652.3975 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 303.1747 634.9282 Tm (7.)Tj ET EMC /P <>BDC BT /TT4 1 Tf 8 0 0 8 312.2906 634.9282 Tm ( )Tj ET EMC /P <>BDC BT /TT2 1 Tf 8 0 0 8 314.5133 634.9282 Tm (Solid drug formulations \(e.g. tablets and capsules\) have been )Tj ET EMC /P <>BDC BT 8 0 0 8 312.2906 623.1282 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 314.5133 623.1282 Tm [(developed with a variety of dif)18.1(ferent release profiles to target )]TJ ET EMC /P <>BDC BT 8 0 0 8 312.2906 611.3282 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 314.5133 611.3282 Tm [(specific areas of the gut. )18.1(These dif)18.1(ferent protective coatings or )]TJ ET EMC /P <>BDC BT 8 0 0 8 312.2906 599.5282 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 314.5133 599.5282 Tm (casings \(which mainly aim to give protection from gastric juices\), )Tj ET EMC /P <>BDC BT 8 0 0 8 312.2906 587.7282 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 314.5133 587.7282 Tm (or modified release casings \(which allow for targeting of specific )Tj ET EMC /P <>BDC BT 8 0 0 8 312.2906 575.9282 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 314.5133 575.9282 Tm (sections of the gut\) must first be broken down to allow liberation of )Tj ET EMC /P <>BDC BT 8 0 0 8 312.2906 564.1282 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 314.5133 564.1282 Tm (the drug \(disintegration\). Once disintegration has occurred, the drug)Tj ET EMC /P <>BDC BT 8 0 0 8 554.65 564.1282 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 312.2906 552.3282 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 314.5133 552.3282 Tm (can form a solution \(dissolution\) for absorption. Some are designed )Tj ET EMC /P <>BDC BT 8 0 0 8 312.2906 540.5282 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 314.5133 540.5282 Tm (to remain intact for several hours and/or only to disintegrate at a )Tj ET EMC /P <>BDC BT 8 0 0 8 312.2906 528.7282 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 314.5133 528.7282 Tm (specified pH \(modified- release/sustained-release preparations\), )Tj ET EMC /P <>BDC BT 8 0 0 8 312.2906 516.9282 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 314.5133 516.9282 Tm (others have mixed profiles, and some have the liberated drugs )Tj ET EMC /P <>BDC BT 8 0 0 8 312.2906 505.1282 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 314.5133 505.1282 Tm (separately coated for targetting purposes. For this reason, )Tj ET EMC /P <>BDC BT 8 0 0 8 312.2906 493.3282 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 314.5133 493.3282 Tm (prolonged or modified release preparations \(e.g., morphine\) )Tj ET EMC /P <>BDC BT 8 0 0 8 312.2906 481.5282 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 314.5133 481.5282 Tm (are best avoided in patients with a SB as they are likely to pass )Tj ET EMC /P <>BDC BT 8 0 0 8 312.2906 469.7282 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 314.5133 469.7282 Tm (through unabsorbed. Ghost tablets are those that have released)Tj ET EMC /P <>BDC BT 8 0 0 8 312.2906 457.9282 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 314.5133 457.9282 Tm (the active drug but appear intact in the stoma output. Drugs with )Tj ET EMC /P <>BDC BT 8 0 0 8 312.2906 446.1281 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 314.5133 446.1281 Tm (artificial sweeteners may increase stool output and thus reduce )Tj ET EMC /P <>BDC BT 8 0 0 8 312.2906 434.3282 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 314.5133 434.3282 Tm (absorption.)Tj ET EMC /P <>BDC BT 8 0 0 8 354.0953 434.3282 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 303.1747 416.8589 Tm (8.)Tj ET EMC /P <>BDC BT /TT4 1 Tf 8 0 0 8 312.2906 416.8589 Tm ( )Tj ET EMC /P <>BDC BT /TT2 1 Tf 8 0 0 8 314.5133 416.8589 Tm (Therapeutic drug monitoring is available for a range of drugs in the )Tj ET EMC /P <>BDC BT 8 0 0 8 312.2906 405.0589 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 314.5133 405.0589 Tm (UK from local and more specialised laboratories \(e.g., rivaroxaban\). )Tj ET EMC /P <>BDC BT 8 0 0 8 312.2906 393.2589 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 314.5133 393.2589 Tm (Many drugs levels can be measured from blood samples that are )Tj ET EMC /P <>BDC BT 8 0 0 8 312.2906 381.4588 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 314.5133 381.4588 Tm (taken at a specific time relating to when taken \(e.g., before a dose )Tj ET EMC /P <>BDC BT 8 0 0 8 312.2906 369.6588 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 314.5133 369.6588 Tm (for carbamazepine \(trough level\) or six hours after a dose for )Tj ET EMC /P <>BDC BT 8 0 0 8 312.2906 357.8589 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 314.5133 357.8589 Tm (digoxin [peak level]\). )Tj ET EMC /P <>BDC BT 8 0 0 8 389.6656 357.8589 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 303.1747 340.3896 Tm (9.)Tj ET EMC /P <>BDC BT /TT4 1 Tf 8 0 0 8 312.2906 340.3896 Tm ( )Tj ET EMC /P <>BDC BT /TT2 1 Tf 8 0 0 8 314.5133 340.3896 Tm (With time, absorption of a drug may improve as intestinal )Tj ET EMC /P <>BDC BT 8 0 0 8 312.2906 328.5895 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 314.5133 328.5895 Tm (adaptations occurs \(e.g., in patients with a jejunum in continuity )Tj ET EMC /P <>BDC BT 8 0 0 8 312.2906 316.7895 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 314.5133 316.7895 Tm [(with a colon\). )55.2(As stoma output reduces there may be improved )]TJ ET EMC /P <>BDC BT 8 0 0 8 312.2906 304.9895 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 314.5133 304.9895 Tm [(absorption of salt, water)55.2(, nutrients and drugs, therefore drug )]TJ ET EMC /P <>BDC BT 8 0 0 8 312.2906 293.1895 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 314.5133 293.1895 Tm (doses may need to be reduced.)Tj ET EMC /P <>BDC BT 8 0 0 8 426.5875 293.1895 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 303.1747 275.5201 Tm (More research is needed in all aspects of drug absorption in patients)Tj ET EMC /P <>BDC BT 8 0 0 8 545.538 275.5201 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 303.1747 263.5201 Tm (with a short bowel.)Tj ET EMC Q endstream endobj 161 0 obj <>/XObject<>/ExtGState<>>> endobj 6 0 obj <> endobj 5 0 obj <> endobj 70 0 obj <>stream Adobed         #"""#''''''''''     !! !!''''''''''""  s!1AQa"q2B#R3b$r%C4Scs5D'6Tdt& EFVU(eufv7GWgw8HXhx)9IYiy*:JZjzm!1AQa"q2#BRbr3$4CS%cs5DT &6E'dtU7()󄔤euFVfvGWgw8HXhx9IYiy*:JZjz?lٳ_ |6lٳf]6lٳdʾJffT OrW!>~KfKy5 xg9(vlٲ?= 8R5/2**3Oag7ռk~{ G8;aœ[, Njۭ{ٳflZ|qmd@i7i6S9?򥞮Q{j%˫D=r[{+IYxËDX@qU{āeٳflV {D6<َ5. )PHLjI 6l̓u Vқc==x& 2FR0p.zw߈ٳbyhM-nJ k@F" q1YkCTЕ-͔TڌKD΋Ywmi40G&$c1!1>)>,Kf͐4/˿=뫲⳧ݾ?ڳ'1I0-)%*6,&=6= 4Sd#ՏJ#C{yٳg"f?2_7"Rhb?PH߮;Gx*1ʁRyi:qBϛ+$kj4(1'3=>} KqF0ŏ+Gf͜cϯi .^s$Svױ_Gr/ ^\yFsi@K>eݒ.[ ~Ԯo?1<48BNO8ni|/<$$(0yu|kM}N,m98,pK̵fݛ6l"Ӽaΐ"Oo=*%u9:ԭ.m3Xt򟔴tNK+{hnڒ?ܻW@.ZyR$GJX+kmU0 9>;.ٳdW-z\F@*+!r ˍZ[@fDK#qݽ:>д3jfK0F$n4h?>fݘ/e4Qii)͎Yj>1O(7~Jٳg>ܾI$bB4}A F37OOd )Q&e*2:0j#<嘴]y5K4 i*Τz7s~L;iŬ'bjOOe}_zqG}=1.!0?f͚͜V)o4l1.,xڒիDGk #Ut]_NճepɺSދOh{ts8I?+\?!jE=CeGN;fiqY|رBczHCiWBٳaG卾^_Ei#F(-Ya]_NSO{S4ٴmZIy-1J4=x{7_tpQtLQf͛f͛<݃f͛6lثf͛6lثf͛6lثf͞ev~QЭ[Xo9/ p^[ IdUMcZҷ&-opIVK[/NG,=O2>Qc5I|Xz~f̀!`H.$O=̏R y-|Ez}R:uytǿpWΧ؍SG4[?f5>hc;˳(rf {6lͺM5Mnj_v2yo]E%{q"D} hHbmG`=[mGq@Ht-pe"Z2Hߺb¼>0(j<+  FqBT+;6lW\ KV+hE9,FuE>sbмOѽ9,ͣı滾.XeZ8E16l(w/~L~lK8r AW \HOjZM3Z|ڗo0*ݽkQ'žX58a)Deg.qvlٳҙkX25@i 5a2X>k78C`H>s]b' 1LL2r6l͛6xCSf͛6lثf͛6lثf͛6lثf͝qi׳;Qaq@P8|dEsӠ62~`灣eH2:XFz_Z͓G\Do7L4fK!N7LD轈]Bٳd[̷;wUBHI#pG|յ7rӢ њ )##z6ڇ"ިᐎ[·8_7I_6ZIw\^xʵ52ZHh{_ct]ri˓Ø 3_vlٲ9K)yMZZ;RC}e:lz:e{3b0|4W47&#j \Nb9)~Y9+SYZ? ?n>s?|I.a+*Zj/O7 ǺǶq=YoDu'&C?N._z\d+qٳf΃47OCg^ w\^ 8;+@~E4Fd[ƆQڈԟB34ũfi<٤FyniFact~J=E-;ы+92GoƧڮĈ_o6.͛66ͩMyuVVZr$i}b9EiEEYEv| -*kխⷚkAKIPRD#! 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