Pharmacokinetic drug interaction

A- Absorption

1

Pharmacodynamic (PD)

• Affects drug action directly

Pharmacokinetic (PK)

• Affects plasma conc. with time (ADME)

Retrospective VS prospective

2

When the precipitant drug affects at least one of the following:

A. Absorption B. Distribution C. Metabolism D. Excretion Of the object drug Change in object drug’s

plasma conc. (Cp)

3

A- Absorption

4

1. Adsorption 2. Complexation/ chelation 3. GI PH change 4. GI motility change 5. Malabsorption 6. Action on bacteria flora

5

6

Object drug Precipitant drug

Concomitantly administered oral drugs

Kaolin, Charcoal or antacids

1. Adsorption

2. Complexation/ chelation

3. GI PH change

4. GI motility change

5. Malabsorption

6. Action on bacteria flora

7

8

Chelation

M

L L

outcome Drug B Drug A

Non-absorbable complex

Warfarine Digitalis Thyroid

cholestyramine

Poorly soluble chelate

Tetracycline Al+3, Ca +2, Mg +2, Fe +2, Bi+2, Zn +2

9

1. Adsorption 2. Complexation/ chelation 3. GI PH change 4. GI motility change 5. Malabsorption 6. Action on bacteria flora

10

11

Acid + base = Salt (ionized) A- B+ A- B+

Absorbable form of most drugs is the non-ionized

form

result ionization Agent

increasing

PH

Drug

absorption

(extent)

increased Antacid, PPI, H2#

Weak acid

absorption

(extent)

decreased Antacid, PPI, H2#

Weak base

absorption

(extent) ????

decreased Antacid, PPI, H2#

Ketononazole (poorly sol. Weak base)

12

13

Aspirin + Omeprazole

Amphetamine + Cimetidine

Ketoconazole + Alomag

14

1. Adsorption 2. Complexation/ chelation 3. GI PH change 4. GI motility change 5. Malabsorption 6. Action on bacteria flora

15

16

1) Readily soluble drugs

Ex. Captopril and Astemizole + Anticholinergic Rate of absorption (Atropin, propantheline, TCA, PZ& pethidine)

+ Prokinetics Rate of absorption (Metoclopramide, Domperidone & cisapride)

17

2) Poorly soluble drugs

Ex. Digoxin and dicumarol + Anticholinergic extent of (Atropin, propantheline, TCA, PZ& pethidine) absorption + Prokinetics extent of (Metoclopramide, Domperidone, cisapride) absorption

18

3) Actively transported drugs

blood

19

GI lumen

Receptor

Drug

intestine

3) Actively transported drugs

Ex. Riboflavin + Anticholinergic extent of (Atropin, propantheline, TCA, PZ pethidine) absorption + Prokinetics extent of (Metoclopramide, Domperidone, cisapride) absorption

20

4) Acid labile drugs & drugs

undergoing GI metabolism

Ex. Of acid labile: antibiotics Ex. Of GI metabolizing drugs: L-dopa + Anticholinergic extent & rate of (Atropin, propantheline, TCA, PZ pethidine) absorption + Prokinetics extent & rate of (Metoclopramide, Domperidone, cisapride) absorption

21

5) Potent single dose drugs

Ex. Hypnotics & analgesics + Anticholinergic rate & effect of (Atropin, propantheline, TCA, PZ pethidine) absorption + Prokinetics rate & effect of (Metoclopramide, Domperidone, cisapride) absorption

22

1. Adsorption 2. Complexation/ chelation 3. GI PH change 4. GI motility change 5. Malabsorption 6. Action on bacteria flora

23

outcome Object drug Precipitant drug

Extent of absorption

Concomitant oral drugs

Neomycin, MTX, Amino salicylic acid, Cytotoxic agents,

5-FU

24

1. Adsorption 2. Complexation/ chelation 3. GI PH change 4. GI motility change 5. Malabsorption 6. Action on bacteria flora

25

26

Bacteria flora Warfarin synthesizes vit. K Vit. K antagonist coagulation coagulation

bleeding

Antibiotics